MinTankesmie

- Mitokondriesykdommer - hyppigere enn antatt?

Mitochondrial pharmacology (Mitokondirefarmakologi)
Trends Pharmacol Sci. 2012 Apr 18. [Epub ahead of print]
Abstract Mitochondria are being recognized as key factors in many unexpected areas of biomedical science. In addition to their well-known roles in oxidative phosphorylation and metabolism, it is now clear that mitochondria are also central to cell death, neoplasia, cell differentiation, the innate immune system, oxygen and hypoxia sensing, and calcium metabolism. Disruption to these processes contributes to a range of human pathologies, making mitochondria a potentially important, but currently seemingly neglected, therapeutic target. Mitochondrial dysfunction is often associated with oxidative damage, calcium dyshomeostasis, defective ATP synthesis, or induction of the permeability transition pore. Consequently, therapies designed to prevent these types of damage are beneficial and can be used to treat many diverse and apparently unrelated indications. Here we outline the biological properties that make mitochondria important determinants of health and disease, and describe the pharmacological strategies being developed to address mitochondrial dysfunction. (...)

Mitokondriesykdommer - hyppigere enn antatt?
Tidsskr Nor Lægeforen 2007; 127: 279
Mutasjoner i POLG-genet kan gi opphav til en rekke kliniske symptomer. En norsk forskergruppe står sentralt i dette kartleggingsarbeidet.

Mitokondriesvikt grunnet defekt i respirasjonskjeden gir alvorlige sykdommer som rammer både barn og voksne. Arvelig mitokondriesykdom kan skyldes mutasjoner i mitokondrie-DNA (mt-DNA) eller mutasjoner i cellekjerne-DNA. Mutasjoner i kjerne-DNA, slik som polymerase gamma (POLG), fører til defekter i mt-DNA og dermed respirasjonskjedesvikt. (...)

Nå har forskerne publisert en ny studie med 26 pasienter med mutasjoner i polymerase gamma, hvorav 25 er norske og én italiensk (2). Studien omfattet to POLG-mutasjoner, 1399G>A og 2243G>C. Disse forårsaker et klinisk spektrum som omfatter aggressiv epilepsi med høy risiko for status epilepticus, ataksi og Alpers’ syndrom.

- Vi kunne for første gang vise at det var forskjell mellom POLG-genotypene. Pasienter som var homozygote for enten 1399G>A og 2243G>C, gjorde det bedre enn dem som hadde én av hver, såkalte blandede heterozygoter. Dette tyder på en dominant negativ effekt, sier professor Laurence Bindoff ved Institutt for klinisk medisin, Seksjon for nevrologi, Universitetet i Bergen.

- POLG-mutasjoner forekommer hyppig. I Norge er ca. en av 50 personer bærere av en av disse to mutasjonene (1). Det ser ut til at noen heterozygoter kan manifestere problemer med epilepsi, parkinsonisme og nevropati i godt voksen alder. Behandling med natriumvalproat er kontraindisert ved POLG-mutasjoner, ettersom slik behandling induserer leversvikt og død. Forskning på dyremodeller har også vist at POLG-mutasjoner kan ha en rolle i aldringsprosessen, sier Bindoff. (...)

(Anm: Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations. Neurology. 2005 Apr 12;64(7):1204-8.

The spectrum of clinical disease caused by the A467T and W748S POLG mutations: a study of 26 cases. Brain 2006; 129: 1685 - 92.)

Mitochondrial diseases (Mitokondriesykdommer)
Lancet. 2012 Apr 4. [Epub ahead of print]
Abstract Mitochondria have a crucial role in cellular bioenergetics and apoptosis, and thus are important to support cell function and in determination of cell death pathways. Inherited mitochondrial diseases can be caused by mutations of mitochondrial DNA or of nuclear genes that encode mitochondrial proteins. Although many mitochondrial disorders are multisystemic, some are tissue specific-eg, optic neuropathy, sensorineural deafness, and type 2 diabetes mellitus. In the past few years, several disorders have been associated with mutations of nuclear genes responsible for mitochondrial DNA maintenance and function, and the potential contribution of mitochondrial abnormalities to progressive neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease has been recognised. The process of mitochondrial fission-fusion has become a focus of attention in human disease. Importantly, the mitochondrion is now a target for therapeutic interventions that encompass small molecules, transcriptional regulation, and genetic manipulation, offering opportunities to treat a diverse range of diseases. (...)

Mitochondrial mutations: newly discovered players in neuronal degeneration
Neuroscientist. 2011 Dec;17(6):645-58.
Abstract Mutations in mitochondrial DNA cause a number of neurological diseases with defined neuropathology; however, mutations in this genome have also been found to be important in a number of more common neurodegenerative diseases. In this review, the authors discuss the importance of mitochondrial DNA mutations in a number of different diseases and speculate how such mutations could lead to cell loss. Increasing our understanding of how mitochondrial DNA mutations affect mitochondrial metabolism and subsequently result in neurodegenerative disease will prove vital to the development of targeted therapies and treatments. (...)

Mitochondrial Disease*
A Pulmonary and Critical-Care Medicine Perspective
Chest. 2001;120:634-648
Det kliniske spektrum av mitokondriesykdommer har ekspandert drastisk det siste tiåret. Uregelmessig mitokondriafunksjon er nå antatt å opptre i en rekke vanlige sykdommer hos voksne, som streker seg fra treningsintoleranse til aldring. Denne gjennomgangen beskriver de vanlige presentasjoner av forekomster av mitokondriesyksommer på akuttmottak og pasienter og diskuterer dagens diagnostiske og terapeutiske valgmuligheter som de opptrer for pulmonary- og intensiv behandling. (...) (The clinical spectrum of mitochondrial diseases has expanded dramatically in the last decade. Abnormalities of mitochondrial function are now thought to participate in a number of common adult diseases, ranging from exercise intolerance to aging. This review outlines the common presentations of mitochondrial disease in ICUs and in the outpatient setting and discusses current diagnostic and therapeutic options as they pertain to the pulmonary and critical-care physician.)

- Telomerer og mitokondria i det aldrende hjerte

Telomeres and mitochondria in the aging heart (Telomerer og mitokondria i det aldrende hjerte)
Circ Res. 2012 Apr 27;110(9):1226-37.
Abstract Studies in humans and in mice have highlighted the importance of short telomeres and impaired mitochondrial function in driving age-related functional decline in the heart. Although telomere and mitochondrial dysfunction have been viewed mainly in isolation, recent studies in telomerase-deficient mice have provided evidence for an intimate link between these two processes. Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and PGC-1β in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging. (...)

Mitokondrie

Mitokondrie; runde eller avlange korn i cytoplasma bygde av samanfalda membranar; er einaste ekstranukleære strukturar der det finst DNA (mtDNA, jf mitokondriell arv); dei er sete for tilverting av energi (oksidasjon av pyruvat og feittsyrer til karbondioksid og NADH som gir elektronar til ATP-syntesen), syntese av visse protein eller lipid m v; ettersom mitrokondriane i spermiane ikkje overlever fertiliseringa, stammar alle mitokondriane i cellene frå mora, dei replikerer sjølvstendig; jf mitokondriell arv EN mitochondrium (pl mitochondria) ET [gr mitos tråd + khondrion gryn] (Kilde: Norsk medisinsk ordbok.)

(Anm: Mitochondrion, (...) Mitochondria are sometimes described as "cellular power plants" because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy. (en.wikipedia.org).)

Mitochondria: More Than Just a Powerhouse
Current Biology 2006;16(14):R551-R560 (July)
Abstract Pioneering biochemical studies have long forged the concept that the mitochondria are the 'energy powerhouse of the cell'. These studies, combined with the unique evolutionary origin of the mitochondria, led the way to decades of research focusing on the organelle as an essential, yet independent, functional component of the cell. Recently, however, our conceptual view of this isolated organelle has been profoundly altered with the discovery that mitochondria function within an integrated reticulum that is continually remodeled by both fusion and fission events. The identification of a number of proteins that regulate these activities is beginning to provide mechanistic details of mitochondrial membrane remodeling. However, the broader question remains regarding the underlying purpose of mitochondrial dynamics and the translation of these morphological transitions into altered functional output. One hypothesis has been that mitochondrial respiration and metabolism may be spatially and temporally regulated by the architecture and positioning of the organelle. Recent evidence supports and expands this idea by demonstrating that mitochondria are an integral part of multiple cell signaling cascades. Interestingly, proteins such as GTPases, kinases and phosphatases are involved in bi-directional communication between the mitochondrial reticulum and the rest of the cell. These proteins link mitochondrial function and dynamics to the regulation of metabolism, cell-cycle control, development, antiviral responses and cell death. In this review we will highlight the emerging evidence that provides molecular definition to mitochondria as a central platform in the execution of diverse cellular events. © 2006 Elsevier Ltd. All rights reserved. (...)

Mitokondriesykdommer

Mitochondrial complex I activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder.
Arch Gen Psychiatry. 2010 Apr;67(4):360-8.
(...) CONCLUSIONS: Impairment of complex I may be associated with increased protein oxidation and nitration in the prefrontal cortex of patients with bipolar disorder. Therefore, complex I activity and mitochondrial dysfunction may be potential therapeutic targets for bipolar disorder. (...)

Mitokondrier påvirker risiko for apopleksi (anm: hjerneslag)
Tidsskr Nor Legeforen 2010; 130:1319 (12.8.2010)
Genetisk variasjon i mitokondriene bidrar til etiologien ved apopleksi og kan brukes til å identifisere personer med høy apopleksirisiko.

Genetiske faktorer spiller en rolle i patogenesen ved iskemisk cerebralt infarkt. I en ny studie viser forskere at genetisk variasjon i den mitokondrielle DNA-subhaplogruppe K er en uavhengig determinant for apopleksirisiko (1). (...)

(Anm: apopleksi, apoplexia cerebri, hjerneslag, akutte fokale nevrologiske symptomer og utfall som varer i mer enn 24 timer og som skyldes skade av hjernevev enten på grunn av regionalt redusert blodsirkulasjon (hjerneinfarkt) eller på grunn av hjerneblødning. Kilde: Store norske leksikon.)

Mitochondria and the Autophagy–Inflammation–Cell Death Axis in Organismal Aging
Science 2011;333(6046):1109-1112 (26 August)
Abstract Alterations of mitochondrial functions are linked to multiple degenerative or acute diseases. As mitochondria age in our cells, they become progressively inefficient and potentially toxic, and acute damage can trigger the permeabilization of mitochondrial membranes to initiate apoptosis or necrosis. Moreover, mitochondria have an important role in pro-inflammatory signaling. Autophagic turnover of cellular constituents, be it general or specific for mitochondria (mitophagy), eliminates dysfunctional or damaged mitochondria, thus counteracting degeneration, dampening inflammation, and preventing unwarranted cell loss. Decreased expression of genes that regulate autophagy or mitophagy can cause degenerative diseases in which deficient quality control results in inflammation and the death of cell populations. Thus, a combination of mitochondrial dysfunction and insufficient autophagy may contribute to multiple aging-associated pathologies. (...)

Functional Modules and Structural Basis of Conformational Coupling in Mitochondrial Complex I
Science 2010;329(5990):448 - 451 (23 July)
(...) Proton-pumping respiratory complex I is one of the largest and most complicated membrane protein complexes. Its function is critical for efficient energy supply in aerobic cells, and malfunctions are implicated in many neurodegenerative disorders. (...)

Genterapi for mitokondriesykdommer?
Tidsskr Nor Legeforen 2009; 129:2578 (17.12.2009)
(...) Mutasjoner i mitokondrielt DNA forårsaker forskjellige sykdommer som myopati, slagliknende episoder, hørselstap og diabetes. Mitokondriesykdommer oppstår hos ca. 1:5 000, men forskning viser at de kan være enda hyppigere. Ny forskning i en apemodell har vist at det er mulig å erstatte ikke-funksjonelt mitokondrielt DNA med frisk mitokondrielt DNA fra en annen donor (1). (...)

– At dette er blitt teknisk mulig, er svært spennende, da det foreløpig ikke finnes gode behandlingsmuligheter for de aller fleste mitokondriesykdommer, sier professor Laurence Bindoff ved Nevrologisk avdeling, Haukeland universitetssykehus. (...)

Drilling for Energy in Mitochondrial Disease
Arch Neurol. 2009;66(8):931-932 (August)
The catalog of mitochondrial and nuclear DNA mutations that impair the synthesis, assembly, or maintenance of proteins necessary for the function of the mitochondrial respiratory chain is large and growing¹; and mitochondrial dysfunction due to mechanisms that are not yet completely understood likely play important roles in numerous degenerative diseases, including amyotrophic lateral sclerosis and Alzheimer, Parkinson, and Huntington diseases.² The manner in which mitochondrial disease impairs cellular function and viability is multifaceted and includes increased production of reactive oxygen species with oxidative degradation of proteins, lipids, and DNA; initiating or accelerating programmed cell death; and limiting cellular energy availability by restricting the rate of oxidative phosphorylation. The energy crisis that accompanies impaired function of the respiratory chain has generally been considered to be the central pathophysiologic mechanism of mitochondrial disease, and attempts to augment cellular energy production have been the focus of most therapeutic trials in mitochondrial disease. (...)

Single Mutation in Mitochondrial DNA Weakens Heart, Muscles
healthfinder.gov 14.2.2008
Changes in tissue similar to effects of aging, report suggests. (...)

THURSDAY, Feb. 14 (HealthDay News) -- A single change in the DNA of mitochondria -- the cellular power plants that generate energy in all human cells -- has been found to cause degenerative heart and muscle disease in mice, a new study says.

Mice harboring the mutation appeared normal early in life, but after a year, they developed marked muscle and heart disease, similar to what can develop in humans, according to University of California, Irvine, researchers. Their findings are published in the Feb. 15 issue of Science.

The study provides further proof that the mitochondria play a central role in human health, the researchers wrote. (...)

The Muscular Dystrophy Association has more about mitochondrial disorders.

(Anm: A Mouse Model of Mitochondrial Disease Reveals Germline Selection Against Severe mtDNA Mutations. Science 2008;319(5865):958-962).)

- Mitokondriedefekter

A Lethal Defect of Mitochondrial and Peroxisomal Fission
NEJM 2007;356:1736-1741 (April 26)
We report on a newborn girl with microcephaly, abnormal brain development, optic atrophy and hypoplasia, persistent lactic acidemia, and a mildly elevated plasma concentration of very-long-chain fatty acids. We found a defect of the fission of both mitochondria and peroxisomes, as well as a heterozygous, dominant-negative mutation in the dynamin-like protein 1 gene (DLP1). The DLP1 protein has previously been implicated, in vitro, in the fission of both these organelles. Overexpression of the mutant DLP1 in control cells reproduced the fission defect. Our findings are representative of a class of disease characterized by defects in both mitochondria and peroxisomes. (...)

Mitochondria Defect
JAMA. 2006;296:2307.
Research on mice with mutated mitochondria may help explain some cases of infertility among human males (Nakada K et al. Proc Natl Acad Sci U S A. 2006;103:15148-15153).

In the study, the researchers created male "mito-mice" with different levels (from less than 10% to more than 80%) of mutant mitochondrial DNA. Mice with more than 70% mutant mitochondria had difficulty undergoing meiosis, the process through which sperm are produced. In addition, the sperm that the animals did produce had increased morphological abnormalities and decreased swimming ability.

New research suggests that some male infertility might be caused by defective respiratory function in mitochondria. (Photo credit: P.M. Motta and T. Naguro/www.sciencesource.com)

The researchers concluded that mitochondrial respiration activity is essential for mammalian spermatogenesis and suggested that "some cases of human male infertility with unknown etiology might result from mitochondrial respiratory dysfunction." (...)

New research suggests that some male infertility might be caused by defective respiratory function in mitochondria. (Photo credit: P.M. Motta and T. Naguro/www.sciencesource.com)

The researchers concluded that mitochondrial respiration activity is essential for mammalian spermatogenesis and suggested that "some cases of human male infertility with unknown etiology might result from mitochondrial respiratory dysfunction." (...)

Mitochondrial Dynamics in Disease
NEJM 200/;356:1707-1709 (April 26)
Mitochondria are subcellular organelles that coordinate numerous metabolic reactions, including those of the respiratory complexes that produce the ATP that powers cellular reactions. They have often been depicted as static, with a kidney-bean shape, but there is a growing appreciation of their dynamic nature.1,2 Moreover, they are strikingly varied in structure, ranging from small, spherical particles to long, interconnected filaments. Mitochondria are also highly motile and constantly move in a directed manner along cytoskeletal tracks within cells.

An individual mitochondrion is not an autonomous organelle. The hundreds of mitochondria within a typical cell undergo continual cycles of . . . [Full Text of this Article] (...)

- Mitokondriemekanismer for sykdom ved diabetes mellitus

Mitochondrial Mechanisms of Disease in Diabetes Mellitus (Mitokondriemekanismer for sykdom ved diabetes mellitus)
medpagetoday.com 22.3.2012
(...) • Much data support the concept that proper mitochondrial function is required for adequate glucose-induced insulin secretion.
• Treatment strategies that focus on increasing mitochondrial function could represent important new approaches in the treatment of diabetes.
Mitochondria are found in every cell in the human body.¹ Known as the “power plant of the cell,” mitochondria are central to the conversion of fatty acids and glucose to usable energy in the form of ATP (adenosine triphosphate).¹, ² A growing body of evidence now demonstrates a link between various disturbances in mitochondrial functioning and type 2 diabetes.¹

In patients with type 2 diabetes, the size, number, and efficiency of mitochondria are reduced.3 This can have pathogenic effects in the tissues central to glucose metabolism — the pancreas, liver, and skeletal muscle.

In pancreatic beta cells, mitochondria are central to insulin secretion. As the amount of glucose in the circulation increases, so does the mitochondrial production of ATP inside the cell. When this occurs, ATP-sensitive channels open, leading to membrane depolarization and the secretion of insulin.¹

Much data support the concept that mitochondrial function is required for appropriate glucose-induced insulin secretion.4 Studies in beta cell lines have shown that when mitochondrial function is experimentally decreased, insulin secretion shows a similar reduction.⁴ Supporting studies in humans have shown that individuals with disabling mutations in mitochondrial DNA (i.e., the A32433G mutation) demonstrate impaired pancreatic insulin secretion in response to glucose challenge.

Mitochondrial dysfunction in skeletal muscle and the liver might also contribute to the development of diabetes. As part of its cellular respiratory function, mitochondria utilize (and break down) fatty acids. When mitochondrial function is reduced, intracellular fats may accumulate.² (...)

- Hos pasienter med Parkinsons sykdom er aktiviteten for mitokondrier og elektrontransport forstyrret med det resultat at de ikke lenger produserer tilstrekkelig energi for cellen

Vitamin K2: New hope for Parkinson's patients? (Vitamin K2: Nytt håp for pasienter med Parkinsons sykdom)
worldpharmanews.com 14.5.2012
Neuroscientist Patrik Verstreken, associated with VIB and KU Leuven, succeeded in undoing the effect of one of the genetic defects that leads to Parkinson's using vitamin K2. His discovery gives hope to Parkinson's patients. This research was done in collaboration with colleagues from Northern Illinois University (US) published on the website of the authorative journal Science.

"It appears from our research that administering vitamin K2 could possibly help patients with Parkinson's. However, more work needs to be done to understand this better," says Patrik Verstreken.

If we looked at cells as small factories, then mitochondria would be the power plants responsible for supplying the energy for their operation. They generate this energy by transporting electrons. In Parkinson's patients, the activity of mitochondria and the transport of electrons have been disrupted, resulting in the mitochondria no longer producing sufficient energy for the cell. This has major consequences as the cells in certain parts of the brain will start dying off, disrupting communication between neurons. The results are the typical symptoms of Parkinson's: lack of movement (akinesia), tremors and muscle stiffness.

The exact cause of this neurodegenerative disease is not known. In recent years, however, scientists have been able to describe several genetic defects (mutations) found in Parkinson's patients, including the so-called PINK1 and Parkin mutations, which both lead to reduced mitochondrial activity. By studying these mutations, scientists hope to unravel the mechanisms underlying the disease process. (...)

(Anm: Vitamin K2 Is a Mitochondrial Electron Carrier That Rescues Pink1 Deficiency. Science. 2012 May 10. [Epub ahead of print].)

Miljømessige effekter på mitokondrier

Suggestive evidence on the genetic link between mitochondria dysfunction and autism
Acta Psychiatrica Scandinavica 2010;123(2):95 ( February) (...)

Autismefare nær motorvei
aftenposten.no 4.1.2011
Foreldre som bor i nærheten av en travel motorvei har dobbelt så stor fare for å få barn med autisme enn foreldre som bor langt unna slike veier, viser en undersøkelse publisert i amerikanske Environmental Health Perspectives. Foreldre nær travle bygater har imidlertid ikke den samme tendensen, uten at forskerne ved Saban Research Institute of Children’s Hospital Los Angeles har gode forklaringer på forskjellen. Les mer på http://healthland.time.com. (...)

Mito-Conundrum: Unraveling Environmental Effects on Mitochondria
Environ Health Perspect 2010;118:a292-a297
Look into any cell today, and you’ll see remnants of ancient bacteria by the thousands. These mitochondria—tiny organelles in the cell that each possess their own DNA—have come under a growing scientific spotlight; scientists increasingly believe they play a central role in many, if not most, human illnesses. Exquisitely sensitive to environmental threats, mitochondria convert dietary sugars into a high-energy molecule—adenosine triphosphate (ATP)—that cells use as fuel. And when mitochondria falter, cells lose power, just as a flashlight dims when its batteries weaken. Now scientists are linking environmental interactions with the mitochondria to an array of metabolic and age-related maladies, including cancer, autism, type 2 diabetes, Alzheimer disease, Parkinson disease, and cardiovascular illness. (...)

(Anm: Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 2010.)

Genterapi mot mitokondriesykdom?

Parasitt-RNA i genterapi mot mitokondriesykdom?
Tidsskr Nor Lægeforen 2007; 127: 11 (4.1.2007)
Protozoer som er i stand til å importere tRNA inn i mitokondriene, kan gi nye muligheter for behandling av mitokondriesykdommer hos mennesker.

Mutasjoner i mitokondrienes tRNA-gener er forbundet med flere uhelbredelige nevromyopatier og stoffskiftesykdommer nedarvet fra mor. De cellulære konsekvensene av slike mutasjoner er svekket mitokondriell proteinsyntese og akkumulering av unormale translasjonsprodukter. For å helbrede mitokondriesykdommer er søkelyset rettet mot mekanismer som kan tilføre funksjonelt tRNA til de dysfunksjonelle mitokondriene. (...)

- Masserer genene (- massasje demper betennelse som følger etter trening og fremmer raskere heling)

Masserer genene
aftenposten.no 10.2.2012
Nå har forskere funnet ut hvorfor massasje lindrer verkende muskler: Massasjen setter i gang gener som hjelper musklene i å helbredes og stopper gener knyttet til betennelse. I en studie hvor forskere undersøkte vev av masserte lår, fant de større grad av cellereparasjon enn i ikke-masserte lår og mer av gener som stimulerer mitokondriene, de deler av cellene som forbrenner energi, til å formere seg. Altså kan massasje ordineres ved siden av betennelsesdempende medikamenter mot verkende og betente muskler, skriver Science Translational Medicine. (...)

(Anm: Massage's Mystery Mechanism Unmasked Science 2012 (1 February).)

Massage's Mystery Mechanism Unmasked
Science 2012 (1 February)
Massage's healing touch may have more to do with DNA than with good hands. A new study has revealed for the first time how kneading eases sore muscles—by turning off genes associated with inflammation and turning on genes that help muscles heal. The discovery contradicts popular claims that massage squeezes lactic acid or waste products out of tired muscles and could bring new medical credibility to the practice.

Despite massage's widespread popularity, researchers know surprisingly little about its effects on muscles. Past studies have managed to show only that a well-administered rub can reduce pain, but none has ever pinpointed how. The scant evidence makes many physicians unsure, if not outright skeptical, of the method. (...)

The results, published online today in Science Translational Medicine, suggest that massage suppresses the inflammation that follows exercise while promoting faster healing. "Basically, you can have your cake and eat it too," Tarnopolsky says. He adds that the study found no evidence to support often-repeated claims that massage removes lactic acid, a byproduct of exertion long blamed for muscle soreness, or waste products from tired muscles.

"This is probably the best study I've seen that looks at the biological basis for massage therapy," says Thomas Best, a sports medicine physician at Ohio State University in Columbus, who has studied massage's effects on animals. He notes that it would be a hard experiment to reproduce because no two massages are identical, but he calls the results "compelling" nonetheless.

Tarnopolsky, for one, is a convert. "There's no question I'm going to be visiting the massage therapist more often," he says. (...)

Massage Therapy Attenuates Inflammatory Signaling After Exercise-Induced Muscle Damage
Sci Transl Med 2012;4(119):119ra13 (1 February)
Abstract Massage therapy is commonly used during physical rehabilitation of skeletal muscle to ameliorate pain and promote recovery from injury. Although there is evidence that massage may relieve pain in injured muscle, how massage affects cellular function remains unknown. To assess the effects of massage, we administered either massage therapy or no treatment to separate quadriceps of 11 young male participants after exercise-induced muscle damage. Muscle biopsies were acquired from the quadriceps (vastus lateralis) at baseline, immediately after 10 min of massage treatment, and after a 2.5-hour period of recovery. We found that massage activated the mechanotransduction signaling pathways focal adhesion kinase (FAK) and extracellular signal–regulated kinase 1/2 (ERK1/2), potentiated mitochondrial biogenesis signaling [nuclear peroxisome proliferator–activated receptor γ coactivator 1α (PGC-1α)], and mitigated the rise in nuclear factor κB (NFκB) (p65) nuclear accumulation caused by exercise-induced muscle trauma. Moreover, despite having no effect on muscle metabolites (glycogen, lactate), massage attenuated the production of the inflammatory cytokines tumor necrosis factor–α (TNF-α) and interleukin-6 (IL-6) and reduced heat shock protein 27 (HSP27) phosphorylation, thereby mitigating cellular stress resulting from myofiber injury. In summary, when administered to skeletal muscle that has been acutely damaged through exercise, massage therapy appears to be clinically beneficial by reducing inflammation and promoting mitochondrial biogenesis. (...)

- Hvordan trening trimmer hjernen

How Exercise Jogs the Brain (Hvordan trening trimmer hjernen)
scientificamerican.com 1.3.2012
Physical activity boosts cognition by improving neurons' power supply

The lifelong mental benefits of exercising have long been known, from improving learning in kids to staving off dementia in seniors. Yet how working up a sweat leads to better cognition is much less clear. A study in the Journal of Applied Physiology reveals that the key may lie in the body’s power supply.

Just as a booming metropolis might build new power plants to meet a rising need for electricity, our muscles respond to the demands of exercise by producing new mitochondria, the tiny structures inside cells that supply the body with energy. J. Mark Davis, a physiologist at the University of South Carolina, and his colleagues wondered if brain cells might do the same thing. While studying mice, they found that quantities of a signaling molecule, dubbed by researchers “a master regulator” of mitochondria production, increased in the brain after half an hour a day of treadmill running. The mice’s brain cells also had more mitochondrial DNA—distinct from the regular cellular DNA found in the nucleus—providing “gold standard” evidence of more mitochondria. It appears that the brain “adapts and changes by bringing more of these power­houses” online, Davis says. The increased energy supply allows the brain to work faster and more efficiently.

The finding could help scientists understand how exercise staves off age- and disease-related declines in brain function, because neurons naturally lose mitochondria as we age, Davis explains. Although past research has shown that exercise encourages the growth of new neurons in certain regions, the widespread expansion of the energy supply could underlie the benefits of exercise to more general brain functions such as mood regulation and dementia pre­vention. “The evidence is accumulating rapidly that exercise keeps the brain younger,” Davis says. (...)

SSRI-preparater har uheldige effekter på mitokondrier

Zoloft has adverse effects on yeast cells (Zoloft har uheldig effekt på gjærceller)
dailyprincetonian.com 2.5.2012
Excerpted figure from Perlstein's 'Accumulation of an Antidepressant in Vesiculogenic Membranes of Yeast Cells Triggers Autophagy,' showing (a) representative 60µM sertraline-treated wildtype yeast cell after 5 minutes of treatment; (b) magnification of the cell's vacuole; (c) magnification of the asterisked autophagosome from a; (d) arrows indicating tell-tale double membrane of an autophagosome; (e) an elaborated multilamellar structure from a cell treated with 60µM sertraline for 20 minutes.

New research in the molecular biology department is calling for closer scrutiny of the popular antidepressant sertraline, commonly known as Zoloft. Researchers in the lab of Ethan Perlstein, an associate research scholar at the Lewis-Sigler Institute for Integrative Genomics, shows that Zoloft can affect yeast cells in unexpected ways.

In a report published in PLoS ONE, a journal published by the Public Library of Science on April 18, the researchers showed that Zoloft accumulates in the cell membranes of baker’s yeast cells and triggers autophagy, a protective mechanism whereby cells degrade their own parts and essentially eat themselves. Though this process can be triggered under natural conditions, autophagy as a response to Zoloft is a striking result that suggests the drug may have a number of unexpected side effects, especially given that yeast cells lack serotonin transporters, the usual target of Zoloft.

Perlstein first got involved with this work as a graduate student at Harvard, where he used yeast as a model system to study the genetic complexity of drug response to many compounds. While at Harvard, he introduced a variety of drugs to yeast cells and found that Zoloft was particularly potent at causing cytotoxicity for the yeast cells, a term Perlstein compared to an “overdose.”

“I like to say ‘overdose’ because I think it captures something about these psych drugs and what they are doing,” Perlstein said.

Upon arriving at the University in 2007, Perlstein’s lab began focusing on Zoloft and looking for mutant yeast cells that were resistant to the drug. He classified Zoloft as a selective serotonin reuptake inhibitor, a class of psychoactive drugs intended to be less toxic and safer than those of earlier generations of drugs.
“So these SSRIs were supposed to be safe, and yet we’re finding that these yeast are overdosing quite strongly in response to Zoloft,” he said. (...)

(Anm: Autophagy (en.wikipedia.org).)

(Anm: Accumulation of an Antidepressant in Vesiculogenic Membranes of Yeast Cells Triggers Autophagy. PLoS ONE 2012;7(4): e34024 (April 18).)

Accumulation of an Antidepressant in Vesiculogenic Membranes of Yeast Cells Triggers Autophagy
PLoS ONE 7(4): e34024 (April 18)
Abstract Many antidepressants are cationic amphipaths, which spontaneously accumulate in natural or reconstituted membranes in the absence of their specific protein targets. However, the clinical relevance of cellular membrane accumulation by antidepressants in the human brain is unknown and hotly debated. Here we take a novel, evolutionarily informed approach to studying the effects of the selective-serotonin reuptake inhibitor sertraline/Zoloft® on cell physiology in the model eukaryote Saccharomyces cerevisiae (budding yeast), which lacks a serotonin transporter entirely. We biochemically and pharmacologically characterized cellular uptake and subcellular distribution of radiolabeled sertraline, and in parallel performed a quantitative ultrastructural analysis of organellar membrane homeostasis in untreated vs. sertraline-treated cells. These experiments have revealed that sertraline enters yeast cells and then reshapes vesiculogenic membranes by a complex process. Internalization of the neutral species proceeds by simple diffusion, is accelerated by proton motive forces generated by the vacuolar H+-ATPase, but is counteracted by energy-dependent xenobiotic efflux pumps. At equilibrium, a small fraction (10–15%) of reprotonated sertraline is soluble while the bulk (90–85%) partitions into organellar membranes by adsorption to interfacial anionic sites or by intercalation into the hydrophobic phase of the bilayer. Asymmetric accumulation of sertraline in vesiculogenic membranes leads to local membrane curvature stresses that trigger an adaptive autophagic response. In mutants with altered clathrin function, this adaptive response is associated with increased lipid droplet formation. Our data not only support the notion of a serotonin transporter-independent component of antidepressant function, but also enable a conceptual framework for characterizing the physiological states associated with chronic but not acute antidepressant administration in a model eukaryote. (…)

Fluoxetine interacts with the lipid bilayer of the inner membrane in isolated rat brain mitochondria, inhibiting electron transport and F1F0-ATPase activity (Fluoxetine interagerer med de lipide bilayer i det indre membram i isolerte mitokondrier i rottehjerner, hemmer elektrontransport og F1F0-ATPase aktivitet)
Mol Cell Biochem 1999;199:103-9
Disse resultater viser at fluoxetine indirekte og generelt påvirker elektrontransport og F1F0-ATPase aktivitet hemmer oxidative phosphorylation i isolerte mitokondria i rottehjerner. I tillegg antyder de at disse effekter er mediert ved at legemidlet forstyrrer den fysiske tilstanden i lipid bilayer i det indre mitokondriamembram. (These results show that fluoxetine indirectly and nonspecifically affects electron transport and F1F0)-ATPase activity inhibiting oxidative phosphorylation in isolated rat brain mitochondria. They suggest, in addition, that these effects are mediated by the drug interference with the physical state of lipid bilayer of inner mitochondrial membrane.)

(Anm: fluoxetine (fluoksetin); selges under handelsnavn som Prozac, Fontex, og et hundretalls andre handelsnavn.)

Cancer anti-depressant can also help fight the disease better
onlinenews.com 21.2.2011
ISLAMABAD : Prozac, prescribed to ease the emotional pain of cancer patients, can also help to fight cancer itself. (...)

Prozac, in effect, worked to block the cancer drug from leaving the interior of the cancer cell and poisoning the healthy non-cancerous cells that surrounded it, said a TAU release. The study was published in Cancer Letters. (...)

Antidepressants linked with significant risk of stroke and fracture (Antidepressiva linket til betydelig risiko for hjerneslag og benbrudd)
pulsetoday.co.uk 3.8.2010
Forskrivning av antidepressiva er assosiert med en betydelig økt risiko for slag, fall og benbrudd hos eldre pasienter ifølge analyser av data fra primærhelsetjenesten utført av britiske forskere. (Antidepressant prescribing is associated with a significantly increased risk of stroke, falls and fractures in older people, according to analyses of primary care data by UK researchers.)

Two analyses by the same team of researchers from the University of Nottingham of the QResearch database – a network of 602 practices in England – found antidepressants increased the stroke rate by up to half, the rate of falls by more than three quarters and the fracture rate by 87% compared with no antidepressant use.

Figures from the NHS information Centre show antidepressants are the 10th most commonly prescribed class of drugs in primary care, with 39 million prescriptions issued in England in 2009.

Although depression is common in older people, clinical trials for antidepressants often under-represent the elderly population so little is known about the risks of adverse events in older patients and the relative safety of individual drugs in this class. (...)

(Anm: Mitokondrier påvirker risiko for apopleksi (hjerneslag). Tidsskr Nor Legeforen 2010; 130:1319 (12.8.2010).)

Abuse may trigger gene changes found in suicide victims (Misbruk kan trigge genendringer funnet hos selvmordsofre)
newscientist.com 7.5.2008
Early child abuse may forever change the way genes are expressed in the brain, suggests a postmortem study of people who died by suicide.

It is now well established that it isn't just what genes we inherit, but how they are turned on and off that influences our development. Most of these control switches are thrown before we are born, but some are set in early life, and to a lesser degree, throughout our lives.

Genes are switched off when methyl groups are added to our DNA. Studies have shown that diet, stress and even maternal care can influence these "epigenetic" changes. (...)

"It's an important piece of work," says Craig Cooney at the University of Arkansas in Little Rock. "It points the way toward possible diagnosis and intervention."

Journal references: Nature Neuroscience (vol 7, p 847) and PLoS One (DOI: 10.1371/journal.pone.0002085) (...)

ROS-Generating Mitochondrial DNA Mutations Can Regulate Tumor Cell Metastasis
Science 2008;320(5876):661-6642 (May)
Mutations in mitochondrial DNA (mtDNA) occur at high frequency in human tumors, but whether these mutations alter tumor cell behavior has been unclear. (...)

These results indicate that mtDNA mutations can contribute to tumor progression by enhancing the metastatic potential of tumor cells. (...)

- Lundbeckfonden giver 10 mio. kr. til forskning i livets pumpeværk

På sporet af kroppens balanceakt
lundbeckfonden.dk 8.2.2012
Forsker vil bagom livets pumpeværk
Menneskets krop befinder sig i en konstant kamp for at holde balancen. Ikke blot når vi cykler eller går på line. Hver enkelt celle i vores krop balancerer konstant via utallige biokemiske processer. Himanshu Khandelia fra Syddansk Universitet arbejder med de helt centrale dele af kroppens balance – membranpumperne. Når de svigter, kan det have fatale konsekvenser – ikke blot for den enkelte celle, men for hele kroppen. Blandt andet ved man, at visse hjernelidelser skyldes små fejl i bestemt cellers ionpumper.

Med en bevilling på 10 mio. kroner fra Lundbeckfonden i ryggen, forsøger Himanshu Khandelia nu at finde frem til, hvad der går galt, når pumperne ikke virker. Himanshu Khandelia prøver at forstå disse fejl helt ned på det molekylære niveau.

”Pumperne er jo selve grundlaget for menneskets fysiologi, fordi de styrer transporten ind og ud af vores celler. Alligevel har forskere i årtier ikke kunnet nå til enighed om det helt grundlæggende omkring, hvordan pumperne virker. Ved at kombinere den viden, som vi får fra vores eksperimenter med computersimulationer, vil vi kunne skabe en mere grundlæggende forståelse for pumpernes funktion,” forklarer Himanshu Khandelia. (...)

(Anm: Himanshu Khandelia, PhD. Simulations of Membranes, Membrane Proteins and other Membrane-Associated Phenomena. (memphys.sdu.dk).)

Lundbeckfonden giver 10 mio. kr. til forskning i livets pumpeværk
dagensmedicin.dk 13.2.2012
Den 34-årige forsker Himanshu Khandelia fra Syddansk Universitet har modtaget et Junior Group Leader Fellowship på 10 mio. kr. fra Lundbeckfonden.

Menneskets krop befinder sig i en konstant kamp for at holde balancen. Ikke blot når vi cykler eller går på line. Hver enkelt celle i vores krop balancerer konstant via utallige biokemiske processer.

Himanshu Khandelia fra Syddansk Universitet arbejder med de helt centrale dele af kroppens balance – membranpumperne. Når de svigter, kan det have fatale konsekvenser – ikke blot for den enkelte celle, men for hele kroppen. Blandt andet ved man, at visse hjernelidelser skyldes små fejl i bestemt cellers ionpumper.

Med en bevilling på 10 mio. kroner fra Lundbeckfonden i ryggen, forsøger Himanshu Khandelia nu at finde frem til, hvad der går galt, når pumperne ikke virker. Himanshu Khandelia prøver at forstå disse fejl helt ned på det molekylære niveau.

Via bevillingen kan Himanshu Khandelia opbygge en forskergruppe, der har sin egen helt unikke kombination af teknisk kunnen og dyb indsigt i grundlæggende fysik og kemi.

Selv er han uddannet ved USAs absolut førende universitet inden for kemiteknik - University of Minnesota. Det har gjort ham til en førende ekspert inden for molekylær modellering og simulering. Nu kommer Danmark til at nyde godt af hans viden.

Udover at øge kendskabet til neurologiske lidelser, kan den nye viden om membranpumpernes funktion fx også gøre os klogere på, hvordan antibiotika-resistente bakterier bliver multiresistente. (...)

- Bruk av antidepressiva under svangerskapet linket til høyere risiko for autisme

Antidepressants in Pregnancy and Autism: A Possible Link (Antidepressiva i svangerskapet og autisme: En mulig link)
boston.com 13.11.2011
Studies abound that aim to answer both the question "What causes autism?" and "What is the reason for the increase in incidence and prevalence of autism?" A study published in the November issue of the Archives of General Psychiatry, Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders caught my attention. As both the prevalence of autism and the use of SSRI's (selective serotonin reuptake inhibitors) have increased dramatically in recent years, and SSRI's are powerful medications that act on the brain, the findings do seem plausible. (...)

In this population based study done at the Kaiser Permanente Medical Care Program in Northern California, the researchers found

a 2-fold increased risk of ASD (autism spectrum disorder) associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery, with the strongest effect associated with treatment during the first trimester.

They found that there was no increase in risk for ASD if a mother had been treated for mental health problems but did not receive SSRI's. This finding attempts to answer the question of whether it is the depression or the drug that is associated with ASD. Their findings suggest that it is the drug. (...)

(Anm: Antidepressiva (nytteverdi) (mintankesmie.no).)

Can an increased risk of autism be linked to Paxil? (Kan en øket risiko for autisme linkes til Seroxat (paroxetine)?)
central-pennsylvania.injuryboard.com 15.3.2012
Late last year, a study was published in the Archives of General Psychiatry that suggests a possible link between autism spectrum disorders (ASDs) and maternal use of antidepressant medications during pregnancy. The study—although inconclusive as to a causal link between the two—has gotten quite a bit of attention for the advances it makes in furthering our understanding of what causes ASDs.

The study was aimed at determining whether prenatal exposure to antidepressant medications can be associated with an increased risk of ASD. It was a relatively small study, involving only about 300 children with ASD and 1500 randomly selected children without ASD. The authors concluded that the results suggest that exposure to SSRIs—especially during the first trimester—may “modestly increase the risk of ASD.” The researchers also underscored the need for further studies on this issue, particularly given this study’s small size. (...)

Antidepressant Use During Pregnancy Linked to Higher Risk of Autism (Bruk av antidepressiva under svangerskapet linket til høyere risiko for autisme)
healthland.time.com 5.7.2011 (Time)
Children whose mothers use antidepressants during pregnancy may be more likely to develop autism than kids whose mothers do not, say researchers in California.

In a study involving data on more than 1,800 children — fewer than 300 of whom had an autism spectrum disorder (ASD) — and their mothers, the scientists found that women who were prescribed drugs to treat depression in the year before giving birth were twice as likely to have children with an ASD, compared with women who did not take antidepressants. The risk was even greater for women who were prescribed the drugs in the first trimester: their children were nearly four times more likely to develop autism or a related disorder.

The study focused on one type of antidepressant, selective serotonin reuptake inhibitors (SSRIs), a class of drug that includes fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft). These antidepressants work by increasing available levels of the neurotransmitter serotonin surrounding nerve cells in the brain, which helps boost mood. (...)

Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders (Bruk av antidepressiva under svangerskapet og autisme)
Arch Gen Psychiatry 2011 (Published online July 4)
(...) Results Prenatal exposure to antidepressant medications was reported for 20 case children (6.7%) and 50 control children (3.3%). In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2 [95% confidence interval, 1.2-4.3]), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8 [95% confidence interval, 1.8-7.8]). No increase in risk was found for mothers with a history of mental health treatment in the absence of prenatal exposure to selective serotonin reuptake inhibitors.

Conclusion Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. The potential risk associated with exposure must be balanced with the risk to the mother or fetus of untreated mental health disorders. Further studies are needed to replicate and extend these findings. (...)

- Mitokondriell funksjon er livsviktig i hjerteceller, med mitokondrier som går fra umoden til fullt utviklet tilstand hos foster

Myocytes, Mitochondria, and Maturation (Myocytter, mitokondria, og moding)
Science 14 October 2011: 158. [DOI:10.1126/science.334.6053.158-d]
Understanding the factors and events required for normal heart development will hopefully provide insight into how to treat heart disease and other cardiac abnormalities. Mitochondrial function is essential in cardiac cells, with mitochondria transitioning from an immature to mature state in the embryo. How this occurs, however, is not well understood. During early embryonic development, Hom et al. find that mitochondria alter their length, network complexity, and area, becoming more mature. This corresponds with a decrease in reactive oxygen species in cardiomyocytes and their differentiation. Genetic and pharmacological inhibition showed that these changes are probably the result of the closure of mitochondrial permeability transition pores (mPTPs). mPTP closure increased ATP production needed for myocyte function and drove myocyte differentiation through redox signaling. Thus, the maturation of mitochondria signals cardiomyocyte differentiation. (...)

(Anm: Antidepressiva knyttet til risiko for hjertedefekter hos nyfødte (reuters.com 4.5.2010).)

- Epilepsilegemidler kan øke risiko for autisme

Fetal Exposure to Epilepsy Drug Might Raise Autism Risk: Study
health.yahoo.com 5.12.2011
MONDAY, Dec. 5 (HealthDay News) -- Children exposed to the epilepsy drug valproate have a nearly three times higher risk of having an autism spectrum disorder, new research finds.

Researchers in Denmark used national birth data that included nearly 656,000 children born in that country between 1996 and 2006 to 428,000 women. Using a national prescription drug registry, they identified women who had filled a prescription for valproate (Depakote) shortly before pregnancy through the day of the child's birth.

Using the Danish Psychiatric Register, researchers then identified children who were diagnosed with an autism spectrum disorder, which can include both severe and milder forms of autism, and children with early-onset, more severe autism.

After taking into account certain factors such as maternal age, the child's gender and other factors that influence autism risk, researchers found that children exposed in utero to valproate were 2.6 times more likely to have an autism spectrum disorder and almost five times more likely to have early-onset autism. (...)

Valproate Exposure Associated With Autism, Lower IQ
clinicalpsychiatrynews.com 5.12.2011
BALTIMORE – In utero exposure to valproate appears to increase the risk of significant adverse effects on fetal brain development that persist into childhood.

In two separate studies, children whose mothers took valproate during pregnancy had a higher risk for lower IQ and other cognitive deficiencies, as well as autism and other disorders along the autistic spectrum. "All women with epilepsy of childbearing potential should be informed of the risks. I feel that valproate should not be a first choice antiepileptic drug in women of childbearing potential," Dr. Kimford J. Meador, director of the Emory Epilepsy Center and professor of neurology at Emory University, Atlanta, said in an interview. (...)

- Mitochondria: Aging in a car takes place mainly in the engine

Harvard Scientists Claim to Reverse Aging in Mice
bigthink.com 3.1.2011
While we still haven't quite discovered the fabled Fountain of Youth, a major breakthrough was recently made toward the goal of eternal life. Scientists at Harvard Medical School have discovered that the enzyme telomerase seems to reverse aging in mice.

Inside every cell is a "biological clock"—every time a cell divides, the chromosomes containing our DNA get shorter. At the ends of each chromosome are the telomeres, which are like the tips of our shoelaces, signaling the end of the line. Skin cells, for example, divide about 60 times over their course of their lifespan. When the telomeres become too short after 60 divisions, then the chromosome stops acting properly and eventually dies. This is called the Hayflick limit. So they are, in some sense, programmed to die. (...)

e) Mitochondria: Aging in a car takes place mainly in the engine. Similarly, aging in the cell takes place in its "engine," the mitochondria.
Contrary to the ads we constantly see in drug stores, we can't currently reverse the aging process. But real, testable, falsifiable results are now coming out of laboratories, so it's a good bet that we might be able to stop and perhaps reverse some aspects of aging in the future. (...)

(Anm: Telomerase reverses ageing process - Dramatic rejuvenation of prematurely aged mice hints at potential therapy. Nature 2010 (Published online 28 November).)

Gamle mus ble som unge
nrk.no 11.12.2010
Aldrende mus ble som unge igjen ved aktivering av ungdoms-enzymet telomerase.

Vi lever stadig lenger, men jakten på ungdomskilden pågår stadig for fullt.

Nå mener en amerikansk molekylærbiolog at han har funnet en viktig nøkkel til aldringsgåten.

Ved å aktivere et enzym som påvirker kromosomene har Ronald DePinho fått aldrende laboratoriemus til å bli som unge igjen. (...)

(Anm: Telomerase reverses ageing process - Dramatic rejuvenation of prematurely aged mice hints at potential therapy. Nature 2010 (Published online 28 November).)

- Regelmæssig træning øger antallet af mitokondrier i hjernecellerne hos mus

Motion giver mental gevinst
videnskab.dk 28.9.2011
Regelmæssig træning øger antallet af mitokondrier i hjernecellerne hos mus. Det kan forklare nogle af de mentale gevinster, vi oplever ved at holde kroppen i form, mener forskere.

I hver eneste celle i kroppen er der små kraftværker, kaldet mitokondrier. Her omdannes næringsstoffer til energi, som cellerne skal bruge for at fungere.

Tidligere forskning har vist, at regelmæssig træning øger antallet af mitokondrier i muskelcellerne. Det er blevet brugt som del af forklaringen på mange af de positive fysiske effekter af træning – såsom øget udholdenhed og styrke.

Samtidig er det kendt, at træning også virker positivt på det mentale, for eksempel ved at gøre os mere modstandsdygtige over for stress og depressioner.

Det er uklart, hvilke mekanismer der er bag disse mentale træningseffekter. Forskere fra University of South Carolina fremsætter nu en mulig forklaring.

Træning som behandling for psykiske lidelser
I et studie af mus har de opdaget, at regelmæssig træning øger antallet mitokondrier i hjernecellerne, skriver forskerne i en pressemeddelelse fra The American Physiological Society.

Forskerne tror, dette er med til at styrke udholdenheden under træning ved at gøre hjernen mere modstandsdygtig mod træthed, som påvirker den fysiske ydeevne.

De antyder også, at forøgelsen af antallet mitokondrier i hjernen kan have kliniske implikationer for psykiske lidelser. Måske kan fysisk træning være en del af behandlingen af psykiske problemer?

»Resultaterne kan føre til bedre atletiske præstationer gennem reduceret mental og psykisk udmattelse.«

»De kan også føre til udvidet brug af træning som en terapeutisk mulighed for at svække de negative effekter af ældning, og til at behandle eller forebygge neurodegenerative sygdomme,« skriver forskerne i deres videnskabelige artikel. (...)

(Anm: Mitochondria (mitokondrie). (mintankesmie.no).)

(Anm: Fysisk trening (aktivitet / løping / jogging). (mintankesmie.no).)

(Anm: Exercise Training Increases Mitochondrial Biogenesis in the Brain. Journal of Applied Physiology 2011 (August 4).)

- AIDS-legemidler kan forårsake for tidlig aldring, ifølge studie

AIDS drugs can cause premature ageing: study (AIDS-legemidler kan forårsake for tidlig aldring, ifølge studie)
reuters.com 26.6.2011

(Reuters) - A class of generic AIDS drugs often used to treat HIV in Africa and other poor regions can cause premature aging and lead to age-related illnesses such as heart disease and dementia, scientists said on Sunday.

In a study in the journal Nature Genetics, British researchers found that the drugs, known as nucleoside analog reverse-transcriptase inhibitors, or NRTIs, damage DNA in the patient's mitochondria -- the "batteries" that power cells.

The scientists said it was unlikely that newer cocktails of AIDS drugs made by firms like Gilead, Merck, Pfizer and GlaxoSmithKline would inflict similar levels of damage, since they are thought to be less toxic to mitochondria. But more research is needed to be certain. (...)

The findings do however help explain why HIV-infected people treated with older antiretroviral AIDS drugs sometimes show advanced signs of frailty and diseases such as heart disease and dementia at an early age, the researchers said.

"DNAet i våre mitokondrier blir kopiert i løpet av vår levetid,og når vi eldes akkumuleres feil naturlig," sa Chinnery, som ledet studien. ("The DNA in our mitochondria gets copied throughout our lifetimes and, as we age, naturally accumulates errors," said Chinnery, who led the study.)

"Vi tror disse HIV-legemidler akselererer hastigheten på de feil som bygges opp. Så i løpet av for eksempel 10 år kan en persons mitokondrielle DNA ha akkumulert samme mengde feil som en person som er eldet over 20 eller 30 år." (...) ("We believe these HIV drugs accelerate the rate at which these errors build up. So over the space of, say, 10 years, a person's mitochondrial DNA may have accumulated the same amount of errors as a person who has naturally aged 20 or 30 years." )

The researchers are now looking at ways to repair or stall some of the damage caused by the drugs and say they believe that focusing on exercise -- which appears to have a beneficial effect on patients with mitochondrial diseases -- may help. (...)

(Anm: Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nature Genetics 2011 (Published online26 June).)

(Anm: Mitochondria (mitokondrie). (mintankesmie.no).)

(Anm: aldring Kilde: Store norske leksikon.).)

- Kan trening holde deg ung?

Can Exercise Keep You Young? (Kan trening holde deg ung?)
well.blogs.nytimes.com 2.3.2011
We all know that physical activity is beneficial in countless ways, but even so, Dr. Mark Tarnopolsky, a professor of pediatrics at McMaster University in Hamilton, Ontario, was startled to discover that exercise kept a strain of mice from becoming gray prematurely.

But shiny fur was the least of its benefits. Indeed, in heartening new research published last week in The Proceedings of the National Academy of Sciences, exercise reduced or eliminated almost every detrimental effect of aging in mice that had been genetically programmed to grow old at an accelerated pace.

In the experiment, Dr. Tarnopolsky and his colleagues used lab rodents that carry a genetic mutation affecting how well their bodies repair malfunctioning mitochondria, which are tiny organelles within cells. Mitochondria combine oxygen and nutrients to create fuel for the cells — they are microscopic power generators.

Mitochrondria have their own DNA, distinct from the cell’s own genetic material, and they multiply on their own. But in the process, mitochondria can accumulate small genetic mutations, which under normal circumstances are corrected by specialized repair systems within the cell. Over time, as we age, the number of mutations begins to outstrip the system’s ability to make repairs, and mitochondria start malfunctioning and dying.

Many scientists consider the loss of healthy mitochondria to be an important underlying cause of aging in mammals. As resident mitochondria falter, the cells they fuel wither or die. Muscles shrink, brain volume drops, hair falls out or loses its pigmentation, and soon enough we are, in appearance and beneath the surface, old.

The mice that Dr. Tarnopolsky and his colleagues used lacked the primary mitochondrial repair mechanism, so they developed malfunctioning mitochondria early in their lives, as early as 3 months of age, the human equivalent of age 20. By the time they reached 8 months, or their early 60s in human terms, the animals were extremely frail and decrepit, with spindly muscles, shrunken brains, enlarged hearts, shriveled gonads and patchy, graying fur. Listless, they barely moved around their cages. All were dead before reaching a year of age.

Except the mice that exercised. (...)

(Anm: Fysisk trening (aktivitet / løping / jogging). (mintankesmie.no).)

- The Antidepressant Sertraline Targets Intracellular Vesiculogenic Membranes in Yeast

The Antidepressant Sertraline Targets Intracellular Vesiculogenic Membranes in Yeast.
Genetics. 2010 May 10. [Epub ahead of print]
Abstract Numerous studies have shown that the clinical antidepressant sertraline (Zoloft((R))) is biologically active in model systems, including fungi, which do not express its putative protein target, the serotonin/5-HT transporter, thus demonstrating the existence of one or more secondary targets. Here we show that in the absence of its putative protein target, sertraline targets phospholipid membranes that comprise the acidic organelles of the intracellular vesicle transport system by a mechanism consistent with the bilayer couple hypothesis. Based on a combination of drug-resistance selection and chemical-genomic screening, we hypothesize that loss of vacuolar ATPase activity reduces uptake of sertraline into cells, whereas dysregulation of clathrin function reduces the affinity of membranes for sertraline. Remarkably, sub-lethal doses of sertraline stimulate growth of mutants with impaired clathrin function. Ultrastructural studies of sertraline-treated cells revealed a phenotype that resembles phospholipidosis induced by cationic amphiphilic drugs in mammalian cells. Using reconstituted enzyme assays, we also demonstrated that sertraline inhibits phospholipase A1 and phospholipase D, exhibits mixed effects on phospholipase C and activates phospholipase A2. Overall, our study identifies two evolutionarily conserved membrane-active processes-vacuolar acidification and clathrin-coat formation-as modulators of sertraline's action at membranes. (...)

- Mitochondrial Respiratory Chain Dysfunction

Mitochondrial Respiratory Chain Dysfunction in Muscle From Patients With Amyotrophic Lateral Sclerosis
Arch Neurol. 2010;67(7):849-854 (July)
Background Amyotrophic lateral sclerosis (ALS) is a major cause of neurological disability and its pathogenesis remains elusive despite a multitude of studies. Although defects of the mitochondrial respiratory chain have been described in several ALS patients, their pathogenic significance is unclear.

Objective To review systematically the muscle biopsy specimens from patients with typical sporadic ALS to search for possible mitochondrial oxidative impairment. (...)

Conclusions Our data confirm that the histochemical finding of COX-negative fibers is common in skeletal muscle from patients with sporadic ALS. We did not find a correlation between severity of the oxidative defect and age of the patients or duration of the disease. However, the only patient who underwent a second muscle biopsy did show a correlation between severity of symptoms and worsening of the respiratory chain defect. In 7 patients, the oxidative defect was severe enough to support the hypothesis that mitochondrial dysfunction must play a role in the pathogenesis of the disease. (...)

- Mitokondirier nøkkel til sinnlidelser

Mitochondria Key In Mood Disorders (Mitokondirier er nøkkel til sinnlidelser)
Clinical Psychiatry 2009;37(10):1 (October)
SANTA FE, N.M. — Mitochondrial dysfunction plays a role in recurring mood disorders, and might help explain why most treated patients eventually have relapses or recurrences, according to a leading investigator in psychiatry and pharmacology.

Unipolar and bipolar disorder are not mitochondrial diseases, but both appear to involve mitochondrial dysfunction, Dr. Richard C. Shelton told attendees at an annual psychiatric symposium sponsored by the University of Arizona.

The evidence is strong in bipolar disorder, and emerging in major depressive disorder, he said. Moreover, patients with mitochondrial diseases, such as certain forms of Parkinson's, might be at increased risk of depressive disorders.“Future treatment development may involve modulation of mitochondrial function,” said Dr. Shelton, James G. Blakemore Research Professor of Psychiatry and professor of pharmacology at Vanderbilt Medical Center in Nashville, Tenn. (...)

In another study that compared plasma from patients with major depression with and without melancholia to the plasma of healthy controls, depressed patients had significantly higher antioxidative enzyme and lipid peroxidation levels, he added (J. Affect. Disord. 2001;64:43-51).

As outlined by Dr. Shelton, the relationship between depressive disorders and mitochondrial dysfunction can be traced to the electron transport chain located in the inner membrane of mitochondria. A series of protein complexes, the chain synthesizes adenosine triphosphate. The number of proteins involved and the complexity of the process create “unfortunately lots of places to have problems along the way,” he said. (...)

(Anm: Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord. 2001 Apr;64(1):43-51.)

- Antidepressiva kan skade menns sædceller (DNA)

Anti-depressants can damage men's sperm (Antidepressiva kan skade menns spermie)
chicagotribune.com 12.6.2009
Add anti-depressants to the list of substances that can damage men’s sperm and potentially impair their fertility.

In a new study, New York researchers report that as many as half of men taking the anti-depressant paroxetine (brand names, Seroxat and Paxil) have higher levels of sperm fragmentation.

The study was published online today by the journal Fertility & Sterility.

“It’s fairly well known that SSRI anti-depressants negatively impact erectile function and ejaculation. This study goes on step further, demonstrating that they can cause a major increase in genetic damage to sperm,” said Dr. Peter Schlegel, the study’s senior author and professor of reproductive medicine at Weill Cornell Medical College in New York.

“Although this study doesn’t look directly at fertility, we can infer that as many as half of men taking SSRIs have a reduced ability to conceive. These men should talk with their physicians about their treatment options,” he added. (...)

Dr. Cigdem Tanrikut speculated that the anti-depressant caused mens’ sperm to slow down as it makes its way through the male reproductive tract. Sperm gets “hung up,” she said in a statement, allowing it to age and become damaged.

The amount, concentration and motility of sperm were not significantly changed by the medication.

Though men may not know it, sperm can be damaged by various substances, including smoking, alcohol, heat, anabolic steroids, drug abuse, sexually transmitted diseases and some environmental exposures. (...)

Adverse effect of paroxetine on sperm (Uheldig virkning av Seroxat (paroxetine) på sædceller)
Fertility and Sterility (American Society for Reproductive Medicine)
published online 10 June 2009.
Objective
To assess the effects of a selective serotonin reuptake inhibitor on semen parameters. (...)

Patient(s)
Thirty-five healthy male volunteers, 18–65 years old.
Intervention(s)
Paroxetine administration for 5 weeks. (...)

Conclusion(s)
In men with normal semen parameters, paroxetine induced abnormal sperm DNA fragmentation in a significant proportion of subjects, without a measurable effect on semen parameters. The fertility potential of a substantial number of men on paroxetine may be adversely affected by these changes in sperm DNA integrity. (...)

The Bad Daddy Factor
miller-mccune.com 10.12.2010
Drinking, smoking, taking prescription meds or failing to eat a balanced diet can influence the health of men’s future children. (...)

Drugs can also interfere with sperm transport. A 2009 study revealed that a standard dose of paroxetine — the active drug in the antidepressant marketed as Paxil — causes a fivefold increase in the number of men who show evidence of “sperm fragmentation,” which can increase the chances of miscarriage. Researchers have known that certain antidepressants can influence ejaculatory response; it turns out that they seem to slow the transportation of sperm through the male reproductive system, causing the cells to age prematurely. “Sperm are being damaged because they’re not traveling properly through the body,” says Peter Schlegel, who led the study and is a urologist at New York’s Weill Cornell Medical College. (...)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

Anti-Depressant-Associated Changes In Semen Parameters
medpagetoday.com 28.11.2008
SAN FRANCISCO, CA, USA (UroToday.com) - The authors previously reported an effect of antidepressants on semen parameters. The current study was designed to assess/confirm their prior report of the effects of an SSRI, paroxetine (Paxil), on semen parameters. (...)

As opposed to prior report, semen parameters (volume, concentration, motility, morphology) were not significantly altered during SSRI treatment. However, mean DNA fragmentation TUNEL score was significantly higher on SSRI (30.3%) versus baseline (13.8%). Multivariate logistic regression, correcting for age and body mass index, confirmed that SSRI treatment was significantly correlated with increased DNA fragmentation Up to 35% of men noted significant changes in erectile function and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. (...)

Antidepressants may make men infertile (Antidepressiva kan gjøre menn sterile)
guardian.co.uk 24.10.2006
Bestselling antidepressant drugs may be making some men infertile, research reported yesterday suggested.

The warning follows a study of two men at Cornell Medical Centre in New York whose sperm counts dropped to almost zero while taking the drugs but recovered to healthy levels whenever their medication was suspended.

The men were tested over a two-year period while being treated with the selective serotonin reuptake inhibitors (SSRIs) Citalopram (Cipramil) or Sertraline (Lustral), which belong to the same class of drugs as Prozac and Seroxat, Britain's biggest selling antidepressants. (...)

"These were men with normal sperm counts that went to nearly zero when they were on these antidepressants but returned to normal when they were off them," Prof Schlegel said.

"It's a dramatic effect and it has never been described before. We believe that while it has had a profound effect on these two men, it could be having a significant but more subtle effect on many more." (...)

Svårare bli pappa med antidepressiva
sr.se 26.9.2008
(...) Antidepressiva läkemedel kan göra det svårare för män att få barn. Det tycks bero på att spermierna drabbas av skador i sitt DNA, visar en första, mindre undersökning från Cornell Medical Centre i New York. (...)

Paxil could make men infertile, researchers suggest
pharmatimes.com 25.9.2008
US scientists have claimed that one of the most commonly used selective serotonin re-uptake inhibitors, GlaxoSmithKline's Seroxat/Paxil, causes serious DNA damage in sperm cells, according to the report in New Scientist. (...)

Antidepressants may damage male fertility: study (Antidepressiva kan skade menns fruktbarhet, ifølge studie)
reuters.com 24.9.2008
LONDON (Reuters) - Common antidepressant drugs may reduce some men's fertility by damaging the DNA in their sperm, according to scientists.

A study of 35 healthy men given paroxetine -- sold as Paxil or Seroxat by GlaxoSmithKline -- found that, on average, the proportion of sperm cells with fragmented DNA rose from 13.8 percent before treatment to 30.3 percent after just four weeks.

Similar levels of sperm DNA damage have been linked to problems with embryo viability in couples trying to have children. (...)

Allan Pacey, Senior Lecturer in Andrology at the University of Sheffield, said the apparent increase in sperm DNA damage was "alarming," although he noted the level at which damage becomes clinically significant was open to debate. (...)

Antidepressants Linked to Male Infertility
newsinferno.com 24.10.2006
Researchers at New York’s Cornell Medical Center have found a major correlation between use of antidepressants and sperm count. Men who take selective serotonin reuptake inhibitors (SSRIs) are being urged to consult closely with their doctors in order to determine a proper course of action in light of the new study, the first of its kind. Cornell’s Peter Schlegel announced the results this week at the 62nd annual meeting of the American Society for Reproductive Medicine (ASRM) in New Orleans. (...)

Dr. Schlegel believes that the problem may be connected to damage of the nerves in the vas deferens, the tube trusted with the task of delivering sperm to semen just before ejaculation. For male SSRI patients who may be considering starting or continuing a family, the results may have major ramifications. (...)

(Anm: vas deferens; ductus deferens; jf ev kongenital bilateralt manglande vas deferens EN vas deferens. Kilde: Norsk medisinsk ordbok.)

(Anm: vas deferens; wikipedia.org.)

Prozac is linked to low sperm count (Prozac linket til dårlig sædkvalitet)
timesonline.co.uk 24.10.2006
ANTIDEPRESSANT drugs could lower men’s sperm count, the first investigation of their effect on male fertility has found. (...)

(Anm: Strålingen fra mobiltelefoner kan føre til vesentlig nedsatt sædkvalitet hos menn, antyder en fersk studie. aftenposten.no 24.10.2006.)

Fluoxetine (Prozac) forsinker midlertidig videreutvikling av MS

Fluoxetine (Prozac) Temporarily Slows MS Progression (Fluoxetine (Prozac) forsinker midlertidig videreutvikling av MS)
medpagetoday.com 1.5.2008
GRONINGEN, The Netherlands, May 1 -- The antidepressant drug fluoxetine (Prozac) curbed progression of relapsing-remitting multiple sclerosis in a small placebo-controlled study, but the effect lasted only a few months, researchers here said. (...)

After 16 weeks of double-blind treatment, patients taking 20 mg/day of fluoxetine showed significantly fewer new lesions in MRI scans compared with patients receiving placebo, reported Jop P. Mostert, M.D., of the University of Groningen, and colleagues, online in the Journal of Neurology, Neurosurgery, and Psychiatry.

Twelve of 19 fluoxetine-treated patients had no new gadolinium-enhancing lesions at the 16-week evaluation, compared with five of 19 in the placebo group (P=0.02), they said.

However, the treatment phase lasted 24 weeks, and most measures of disease activity showed no significant differences between the fluoxetine and placebo groups at the study's final evaluation. (...)

(Anm: Effects of fluoxetine on disease activity in relapsing multiple sclerosis: a double-blind, placebo-controlled, exploratory study. J Neurol Neurosurg Psychiatry. Published Online First: 1 May 2008. doi:10.1136/jnnp.2007.139345.)

SSRI-er linket til dårlig sædkvalitet

Anti-Depressant-Associated Changes In Semen Parameters
medpagetoday.com 28.11.2008
SAN FRANCISCO, CA, USA (UroToday.com) - The authors previously reported an effect of antidepressants on semen parameters. The current study was designed to assess/confirm their prior report of the effects of an SSRI, paroxetine (Paxil), on semen parameters. (...)

As opposed to prior report, semen parameters (volume, concentration, motility, morphology) were not significantly altered during SSRI treatment. However, mean DNA fragmentation TUNEL score was significantly higher on SSRI (30.3%) versus baseline (13.8%). Multivariate logistic regression, correcting for age and body mass index, confirmed that SSRI treatment was significantly correlated with increased DNA fragmentation Up to 35% of men noted significant changes in erectile function and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. (...)

Antidepressants may make men infertile (Antidepressiva kan gjøre menn sterile)
guardian.co.uk 24.10.2006
Bestselling antidepressant drugs may be making some men infertile, research reported yesterday suggested.

The warning follows a study of two men at Cornell Medical Centre in New York whose sperm counts dropped to almost zero while taking the drugs but recovered to healthy levels whenever their medication was suspended.

The men were tested over a two-year period while being treated with the selective serotonin reuptake inhibitors (SSRIs) Citalopram (Cipramil) or Sertraline (Lustral), which belong to the same class of drugs as Prozac and Seroxat, Britain's biggest selling antidepressants. (...)

"These were men with normal sperm counts that went to nearly zero when they were on these antidepressants but returned to normal when they were off them," Prof Schlegel said.

"It's a dramatic effect and it has never been described before. We believe that while it has had a profound effect on these two men, it could be having a significant but more subtle effect on many more." (...)

Antidepressants Linked to Male Infertility
newsinferno.com 24.10.2006
Researchers at New York’s Cornell Medical Center have found a major correlation between use of antidepressants and sperm count. Men who take selective serotonin reuptake inhibitors (SSRIs) are being urged to consult closely with their doctors in order to determine a proper course of action in light of the new study, the first of its kind. Cornell’s Peter Schlegel announced the results this week at the 62nd annual meeting of the American Society for Reproductive Medicine (ASRM) in New Orleans. (...)

Dr. Schlegel believes that the problem may be connected to damage of the nerves in the vas deferens, the tube trusted with the task of delivering sperm to semen just before ejaculation. For male SSRI patients who may be considering starting or continuing a family, the results may have major ramifications. (...)

(Anm: vas deferens; ductus deferens; jf ev kongenital bilateralt manglande vas deferens EN vas deferens. Kilde: Norsk medisinsk ordbok.)

(Anm: vas deferens; wikipedia.org.)

Prozac is linked to low sperm count (Prozac linket til dårlig sædkvalitet)
timesonline.co.uk 24.10.2006
ANTIDEPRESSANT drugs could lower men’s sperm count, the first investigation of their effect on male fertility has found. (...)

(Anm: Strålingen fra mobiltelefoner kan føre til vesentlig nedsatt sædkvalitet hos menn, antyder en fersk studie. aftenposten.no 24.10.2006.)

Parkinson linket til mitokondrier

Oxygen Damage May Cause Parkinson's Disease
ivanhoe.com 19.5.2006
(Ivanhoe Newswire) -- A new study reveals damage from oxygen may be one of the main causes of Parkinson's disease.

Researchers from the University of Virginia Health System in Charlottesville found oxygen free radicals are damaging proteins in mitochondria -- the small cellular "batteries" of brain cells. They believe the damage is happening in complex 1 -- a large protein structure, which is the first stop in the electron transport chain.

Researchers analyzed brain cells from deceased Parkinson's patients donated to the UVa brain bank. Results reveal the complex 1 assembly in the brains of Parkinson's patients had 50-percent more damage from oxygen than did normal brains.

Oxygen free radicals are oxygen molecules with an extra electron. In excessive amounts they attack the cell components, including proteins, DNA and lipids in cell membranes. Researchers believe Parkinson's patients may benefit from drugs designed to slow the damage from free radicals.

"If we could soak up the free radicals in mitochondria, then complex 1 could repair itself," says lead researcher Jim Bennett, M.D., Ph.D., a University of Virginia neurologist. "If this damage is caught in people early on, we might interrupt the progression of Parkinson's disease. Such treatment is hypothetical at this point, but it is rational," he concludes.

Researchers are not sure why complex 1 is damaged in Parkinson's patients. They say genetics or environmental toxins could play a role.
This article was reported by Ivanhoe.com, who offers Medical Alerts by e-mail every day of the week.

SOURCE: Journal of Neuroscience, 2006;26:5256-5264.

Gene Linked to Parkinson's Cripples Mitochondria (Gener som får mitokondria til å bryte sammen linket til Parkinsons Sykdom)
healthfinder.gov 3.5.2006
Fruit fly experiments may lead to new treatments, researchers claim.

-- In a breakthrough that may eventually lead to new ways to treat Parkinson's disease, two independent research groups have found that a gene linked to inherited Parkinson's works by disabling a cell's mitochondria.

Mitochondria are the power centers of the cells. They are structures within cells that provide the energy a cell needs to move, divide and produce proteins.
In earlier studies, researchers had found that inherited Parkinson's is caused by mutations in the PTEN-induced putative kinase 1 (PINK1) gene.

Parkinson's disease is a progressive disorder caused by degeneration of nerve cells in the part of the brain that controls movement. First described as "the shaking palsy" in 1817, it affects an estimated 500,000 Americans, with 50,000 new cases reported each year. It is the second most common neurodegenerative disease; only Alzheimer's strikes more people. (...)

Behandling med antidepressiva og litium er assosiert med øket risiko for behandling med antiparkinson- legemidler

Treatment with antidepressants and lithium is associated with increased risk of treatment with antiparkinson drugs: a pharmacoepidemiological study (Behandling med antidepressiva og litium er assosiert med øket risiko for behandling med antiparkinson- legemidler)
J Neurol Neurosurg Psychiatry. 2006 Jun;77(6):781-3
(...) Results: In total, 1 293 789 persons were included. The rate ratio of treatment with APD after treatment with antidepressants was 2.27 (95% CI 2.14 to 2.42) for men and 1.50 (95% CI 1.43 to 1.58) for women. Figures for lithium were almost identical.

Conclusion: Persons treated with antidepressants or lithium are at increased risk of subsequently treatment with APD, showing an association between anxiety/affective disorder and Parkinson’s disease. (...)

Kan fysiske symptomer ved depresjon skyldes lav energiproduksjon

Can Physical Symptoms In Depression Be A Consequence Of Low Energy Production Rates? (Kan fysiske symptomer ved depresjon skyldes lav energiproduksjon)
medicalnewstoday.com 28.3.2008
A report in the March issue of Psychotherapy and Psychosomatics introduces a new hypothesis on the mechanisms of physical symptoms in depression: energy production rates toward the lower end of the spectrum may predispose the individuals to develop depression and physical symptoms.

This hypothesis derives from a study performed in the Karolinska Institute. The Authors hypothesized that decreased ATP production rates in mitochondria underlie depressive disorder with very high levels of somatization. They assessed muscle mitochondria in depressed patients as well as somatic symptomatology with 3 self reported scales (Somatic Anxiety, Muscular and Psychasthenia) from the Karolinska Scales of Personality. At the end of the study, on each of the 3 Karolinska Scales of Personality, virtually every patient with very high levels of somatic symptomatology demonstrated muscle ATP production rates below the control range.

These results demonstrate that mitochondrial function correlates very strongly with self-reported data related to somatic symptoms in depressed patients.

This introduces the possibility that substances such as creatine, coenzyme Q10 and riboflavin may be of help in depression. (...)

(Anm: Mitochondrial Energy Depletion in Depression with Somatization.
Psychother Psychosom 2008;77:127-129.)

(Anm: Creatine (wikipedia.org).)

(Anm: Coenzyme Q10 (wikipedia.org).)

(Anm: riboflavin (wikipedia.org).)

Kan SSRI-preparater forårsake MS-liknende hjerneskader?

Reversal of SSRI-Associated Apathy Syndrome by Discontinuation of Therapy
Ann Pharmacother. 2012 Mar;46(3):e8. Epub 2012 Feb 21.
(...) OBJECTIVE : To report 6 cases of selective serotonin reuptake inhibitor (SSRI)-associated apathy syndrome. CASE SUMMARIES : In all 6 cases, the patient reported loss of motivation while being treated with an SSRI. Loss of motivation was of new onset and temporally associated with the use of the SSRI. A trial of discontinuation of the SSRI was performed in all 6 patients and 2 were started on bupropion while cross-tapering from the SSRI. During the treatment trials, depression and apathy were monitored in all patients. Each case was assessed using the Apathy Evaluation Scale, Clinician version (AES-C), and by evaluating how the patient responded to discontinuation of the SSRI. DISCUSSION : Scores on the AES-C improved significantly in all 6 cases after the SSRI was discontinued. Improvement was also seen in the motivation, novelty, and persistence subdomain scores of the AES-C. A pretreatment AES-C score was available only in the first case. Based on the Naranjo probability scale, there was a probable cause of apathy syndrome with SSRI therapy in the first case and a possible association in the rest of the cases. CONCLUSIONS : In some patients SSRIs may cause an apathy syndrome that can be reversed through discontinuation of the agent. When evaluating patients being treated with an SSRI, clinicians should have a high degree of suspicion and specifically inquire for this iatrogenic form of apathy syndrome. (...)

Antidepressant linked to worsening white matter in elderly (Antidepressiva linket til forverring av hvit substans hos eldre)
rehabpub.com/reuters_article.asp 17.3.2008
NEW YORK (Reuters Health) - The results of a study employing serial cranial MRI suggest that elderly adults who use tricyclic antidepressants may be at increased risk for progression of white matter lesions, which have been linked with late-life depression by previous studies. (...)

The use of an antidepressant from any class during the study period hastened the progression of white matter disease, according to the report in the March issue of Stroke.

Contrary to what the investigators had hypothesized, SSRI use did not reduce, but slightly increased the risk of worsening white matter on multivariate analysis. Still, the 36% increased risk seen with these agents was not statistically significant.

The use of a tricyclic antidepressant, however, was associated with a significantly elevated risk of worsening white matter lesions. Compared with those who used no antidepressants, patients receiving an agent in this drug class had an increased risk of 77%. (...)

(Anm: Antidepressant Treatment and Worsening White Matter on Serial Cranial Magnetic Resonance Imaging in the Elderly. Stroke 2008;39:857-862.)

(Anm: hvit substans; hvit substans, margkledde nervefibrer, utløpere fra nervecellene i hjerne og ryggmarg. Den hvite fargen skyldes myelin, et fettholdig stoff som danner margskjeder omkring nervefibrene. Kilde: Store norske leksikon.)

(Anm: white matter (hvit substans); Multiple Sclerosis (MS) is one of the most common disease which affects white matter (wikipedia.org).)

(Anm: Magnetic resonance imaging MRI findings in white matter disease of brain. J Pak Med Assoc. 2008 Feb;58(2):86-8.)

Selective serotonin reuptake inhibitor use associates with apathy among depressed elderly: a case-control study (Bruk av selektive serotoninreopptakshemmere er assosiert med apati blant deprimerte eldre: en case-control studie)
Annals of General Psychiatry 2007, 6:7
Background (Bakgrunn)
Det er det siste ti år rapportert at bruk av selektive serotoninreopptakshemmere (SSRI-er) kan være assosiert med forekomst av apati. (...) (It has been reported for over the past decade that the use of selective serotonin reuptake inhibitors (SSRI's) may associate with the emergence of apathy.)

Conclusion (Konklusjon)
Selv om depresjon ble bedre hos eldre pasienter som fikk antidepressiva, opptrådte apati oftere hos pasienter som ble behandlet med SSRI enn hos pasienter som ikke ble behandlet. Dysfunksjon i frontal lobe på grunn av serotonerge endringer er ansett som en av mulighetene. (...) (Even though depression was improved in elderly patients receiving antidepressants, apathy appeared to be greater in patients who were treated with SSRI than that found in patients who were not. Frontal lobe dysfunction due to alteration of serotonin is considered to be one of the possibilities.)

(Anm: apati (av gr. nektende a og 'affekt'), psykologisk og psykiatrisk begrep som betyr mangel på sjelelige følelser (affekter). Som regel ledsaget av interesseløshet. Sees særlig ved svære depressive og schizofrene tilstander.

(Anm: pannelappen; lobus frontalis, hjernens frontallapp; jf frontallappssyndromet EN frontal lobe.

frontallappssyndromet; eit særleg huglag (sinnelag) som kan koma etter skade i ein pannelapp i hjernen, t d etter lobotomi; pasienten får eit grunt kjensleliv, vert urimeleg overflatisk og lett til sinns, likesæl og godtruande; også kalla frontal psyke; jf Witzelsucht (ty.) EN frontal lobe syndrome. Kilde: Norsk medisinsk ordbok.)

Vanlige utfall etter ervervet hjerneskade
sunnaas.no 26.2.003
(...) Det er rapportert at noen pasienter blir passive og apatiske. Noen er det fordi de har blitt deprimerte, mens det for andre er et direkte resultat av skaden. Noen blir også urolige og kritikkløse. Ofte er slike endringer i oppførsel det de pårørende synes er vanskeligst å forholde seg til. (...)

THE PEOPLE'S PHARMACY
infoweb.newsbank.com 14.7.2007 (The Dallas Morning News)
Serotonin has become a household word, thanks to Prozac. Millions of people take this popular antidepressant or related drugs such as Zoloft and Paxil every day.

These medications are known scientificallyas SSRIs: selective serotonin reuptake inhibitors. They allow serotonin to accumulate between nerve endings. This brain chemical helps to regulate mood and appears to be important for sleep, learning, appetite, sexual behavior, pain, perception and movement.

But although serotonin is essential for good health, it has a darker side. Too much serotonin can cause bizarre behavior, and some people taking these medications might be at risk of life-threatening drug interactions.

Serotonin syndrome can cause a range of problems, from anxiety, agitation and muscle twitches to nausea, sweating, confusion, convulsions and even coma. (...)

- Forstyrret følesans og opplevelser av "elektriske støt" i hodet" (...) følelse av elektriske støt i hodet, andre blir svimmel og psykisk urolig

Hva er antidepressivt nedtrappingssyndrom?
pasienthandboka.no/ 17.4.2007
Stans i behandlingen med antidepressiv medikasjon (antidepressiva) er noen ganger forbundet med utvikling av et såkalt "antidepressivt nedtrappingssyndrom" (syndrom betyr samling av mange symptomer). Symptomene kan være forkjølelsesliknende, søvnproblemer, kvalme, svimmelhet, forstyrret følesans og opplevelser av "elektriske støt" i hodet. Alle typer antidepressiva er rapportert å kunne gi slike reaksjoner, enten som følge av brå stans eller for rask nedtrapping av behandlingen. De mest brukte antidepressiver betegnes SSRI (Fluoxetin, Fontex, Citalopram, Cipramil, Paroxetin, Seroxat, Sertralin, Zoloft, Fevarin, Cipralex), trisykliske antidepressiver (Klomipramin, Anafranil, Surmontil, Sarotex, Noritren, Sinequan) og MAO-hemmere (Moklobemid, Aurorix). Atypiske antidepressiver er Mianserin, Tolvon, Mirtazapin, Efexor, Edronax, Cymbalta, Yentreve.
Kjennskap til antidepressivt nedtrappingssyndrom er viktig fordi selv om symptomene ofte er milde, kan tilstanden gi mye ubehag, fravær fra jobb, andre psykososiale problemer og unntaksvis kreve sykehusinnleggelse. (...)

SSRI mot depresjon
pasienthandboka.no 27.2.2008
(SSRI betyr selektiv, serotonin reopptaks inhibitor) (...)

Mange er redd for avhengighet ved bruk av nervemedisiner. Medikamentene som brukes ved depresjoner gir ingen ruseffekt eller umiddelbar lykkefølelse, og heller ikke avhengighet (derfor er tilnavnet lykkepiller misvisende). Derimot kan man oppleve ubehag når man slutter med medisinene. Mange beskriver en følelse av elektriske støt i hodet, andre blir svimmel og psykisk urolig. Dette kan være skremmende dersom man ikke vet om det. Denne bivirkningen kan man unngå eller betydelig redusere ved å trappe langsomt ned dosene når man slutter. (...)

Hvilke symptomer ser vi ved MS?

Multiple Sclerosis Symptoms
mult-sclerosis.org
What are the symptoms of Multiple Sclerosis? (...)

(Anm: Antidepressiva (SSRI). (mintankesmie.no).)

Hvilke symptomer ser vi ved MS?
MS.NO 4.12.2002
SYMPTOMER
MS omfatter inflammasjon i sentralnervesystemet som etterfølges av tap av de beskyttende myelin skjedene som omgir nervefibrene [demyelinisering]. Myelinet virker som isolasjonsmateriale som omgir og beskytter elektriske ledninger. Når myelinet tar skade vil ikke nerveimpulsene kunne overføres så hurtig og effektivt som de skal. Som et resultat av den inflammatoriske prosessen vil det oppstå skadde områder [lesjoner eller plaques] i hjerne og ryggmarg som i sin tur gir ulike nevrologiske symptomer.

Vanlige symptomer kan være synstap, nummenhet og vissenhet, kraftsvekkelse, ustø gange, dobbeltsyn, økt trøttbarhet, varmeintoleranse, delvise eller fullstendige lammelser og en fornemmelse av elektrisk støt langs ryggsøylen ved bøyning i nakken. Symptomene kan forsvinne etter et akutt attakk, men kan også bli værende. (...)

(Anm: Antidepressiva (forhøyet kroppstemperatur). (mintankesmie.no).

Serotonin syndrom (SS), kramper, parkinsonisme osv. (forhøyet kroppstemperatur) (mintankesmie.no).)

- Deprimert uten grunn?

Deprimert uten grunn?
nrk.no 23.1.2003 (Schrödingers katt, NRK1)
Opp mot 100 000 eldre mennesker i Norge lider av depresjon. Årsakene er mange og sammensatte, men de er ikke alltid å finne på det psykiske planet. Depresjon kan også ha en fysisk årsak. Australske forskere har funnet at bittesmå umerkelige hjerneslag kan skade de områdene i hjernen som har med sinnstemning og hukommelse å gjøre. - Dette stemmer godt med det vi opplever i den kliniske hverdagen, sier professor i geriatri Olav Sletvold. (...)

Undersøkelser av pasientenes hjerner viste at cellene var skadd og erstattet med vann i bestemte områder av hjernen. Slike endringer er riktignok ikke uvanlige hos eldre mennesker , men omfanget av de hvite flekkene i hjernen var større enn det man kunne vente hos vanlige friske eldre. (...)

Tynne blodårer som forsyner hjernen med blod ble forsnevret eller helt blokkert. (...)

I bunn og grunn har pasientene en rekke bittesmå hjerneslag som de ikke merker selv, men som skader de områdene i hjernen som er avgjørende for hukommelse og sinnstemning. Og det viste seg ganske riktig at de fleste depresjonspasientene også hadde en sykdomshistorie med høyt blodtrykk bak seg. (...)

(Anm: Depresjon, hva er det? (daria.no).)

Statiner

Probing Mitochondria for Statin Myopathy Mystery
medpagetoday.com 25.2.2008
BOSTON, Feb. 25 -- Studies of the mitochondria have offered hints into the etiology of the myopathy that strikes a small percentage of those who take lipid-lowering statins -- heretofore a puzzle for clinicians.

A new way to look at mitochondria devised by Vamsi Mootha, M.D., of Harvard Medical School, and colleagues suggests a cause for the unusual condition and may explain why some studies were unable to find an association.

Dr. Mootha and colleagues reported online in Nature Biotechnology a chemical-genomic method that allows researchers to probe the activity of mitochondria organelles while they are in living muscle cells. (...)

The technique allows them to "read out" several elements of mitochondrial function, including levels of adenosine triphosphate (ATP), production of reactive oxygen species, and electron flux in and out of the organelle, he said.

The method also allows them to monitor expression of about 40 mitochondrial and nuclear genes involved in energy homeostasis, Dr. Mootha said.

"It's a really rich read-out of what's happening to mitochondria in different conditions," Dr. Mootha said. (...)

 

- Legemiddelindusert mitokondriell giftighet

Drug-induced mitochondrial toxicity (Legemiddelindusert mitokondriell giftighet)
Expert Opinion on Drug Metabolism & Toxicology Expert Opinion on Drug Metabolism & Toxicology 2005;1(4): 655-669
Mitochondria play a critical role in generating most of the cell’s energy as ATP. They are also involved in other metabolic processes such as urea generation, haem synthesis and fatty acid β-oxidation. Disruption of mitochondrial function by drugs can result in cell death by necrosis or can signal cell death by apoptosis (e.g., following cytochrome c release). Drugs that injure mitochondria usually do so by inhibiting respiratory complexes of the electron chain; inhibiting or uncoupling oxidative phosphorylation; inducing mitochondrial oxidative stress; or inhibiting DNA replication, transcription or translation. It is important to test for mitochondrial toxicity early in drug development as impairment of mitochondrial function can induce various pathological conditions that are life threatening or can increase the progression of existing mitochondrial diseases. (...)

Serotonin Toxicity as a Consequence of Linezolid Use in Revision Hip Arthroplasty
ORTHOPEDICS 2008; 31:1140
Linezolid is the first in a new group of antibiotics called oxazolidinones. As a potent antimicrobial, it has activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, penicillin-resistant Streptococcus pneumoniae, and macrolide-resistant Streptococci.1 It was originally developed as an antidepressant because it has a weak reversible monoamine oxidase inhibitor effect. There is obvious potential for linezolid to cause serotonin toxicity due to the monoamine oxidase inhibitors properties; however, phase III trials reported no event of this nature.1 Since its release into the worldwide pharmaceutical market, there have been a number of documented case reports of serotonin toxicity2-7 when used in combination with selective serotonin reuptake inhibitors. Common examples of selective serotonin reuptake inhibitors include venlafaxine, citalopram, escitalopram, fluvoxamine, paroxetine, and sertraline. (...)

(Anm: MRSA; Forkortelsen MRSA står for meticillinresistente Staphylococcus aureus. Det vil si gule stafylokokker som er blitt resistente mot de typer antibiotika som oftest brukes mot stafylokokkinfeksjoner.)

Mitochondrial Toxicity Associated with Linezolid (Mitochondrial Toxicity Associated with Linezolid)
NEJM 2005;353:2305-2306 (November 24)
To the Editor: Linezolid belongs to a family of antimicrobial agents (oxazolidinones) that inhibit bacterial protein synthesis by preventing the fusion of 30S and 50S ribosomal subunits.¹ Hyperlactatemia, metabolic acidosis, and peripheral neuropathy are adverse effects of linezolid,^2,3 which could be related to the drug's capacity for interference with mitochondrial function.⁴ We studied mitochondria from three patients in whom asthenia and hyperlactatemia developed during a prolonged course of oral linezolid (600 mg every 12 hours).

Patient 1, a 25-year-old man with Enterococcus faecium infection of a knee prosthesis, received oral linezolid. After three months, mild . . . [Full Text of this Article] (...)

Role of the mitochondrial DNA 16184–16193 poly-C tract in type 2 diabetes
The Lancet 2005; 366:1650-1651 (5 November 2005)
Summary
Recent evidence suggests that polymorphic genetic variation in the non-coding region of mitochondrial DNA (the 16184–16193 polycytosine [poly-C] tract) contributes to the cause of type 2 diabetes, but previous studies only just reached significance. We aimed to investigate this association. We compared patients with type 2 diabetes (n=992) with two independent control groups (n=536, n=1029) from the UK, and saw no difference in the frequency of the 16184–16193 poly-C tract. This finding was confirmed by a meta-analysis of European studies of 1455 patients and 3132 controls (odds ratio 1·16, 95% CI 0·94–1·44). Genetic variation of the 16184–16193 poly-C tract is unlikely to have a major role in the cause of type 2 diabetes.

Partial mitochondrial inhibition causes striatal dopamine release suppression and medium spiny neuron depolarization via H2O2 elevation, not ATP depletion.
J Neurosci. 2005 Oct 26;25(43):10029-40. (PubMed)
Mitochondrial dysfunction is a potential causal factor in Parkinson's disease. We show here that acute exposure to the mitochondrial complex I inhibitor rotenone (30-100 nM; 30 min) causes concentration-dependent suppression of single-pulse evoked dopamine (DA) release monitored in real time with carbon-fiber microelectrodes in guinea pig striatal slices, with no effect on DA content. Suppression of DA release was prevented by the sulfonylurea glibenclamide, implicating ATP-sensitive K+ (KATP) channels; however, tissue ATP was unaltered. Because KATP channels can be activated by hydrogen peroxide (H2O2), as well as by low ATP, we examined the involvement of rotenone-enhanced H2O2 generation. Confirming an essential role for H2O2, the inhibition of DA release by rotenone was prevented by catalase, a peroxide-scavenging enzyme. Striatal H2O2 generation during rotenone exposure was examined in individual medium spiny neurons using fluorescence imaging with dichlorofluorescein (DCF). An increase in intracellular H2O2 levels followed a similar time course to that of DA release suppression and was accompanied by cell membrane depolarization, decreased input resistance, and increased excitability. Extracellular catalase markedly attenuated the increase in DCF fluorescence and prevented rotenone-induced effects on membrane properties; membrane changes were also largely prevented by flufenamic acid, a blocker of transient receptor potential (TRP) channels. Thus, partial mitochondrial inhibition can cause functional DA denervation via H2O2 and KATP channels, without DA or ATP depletion. Furthermore, amplified H2O2 levels and TRP channel activation in striatal spiny neurons indicate potential sources of damage in these cells. Overall, these novel factors could contribute to parkinsonian motor deficits and neuronal degeneration caused by mitochondrial dysfunction.

Mitochondrial biology gets a new chaperone
medicalnewstoday.com 5.10.2005
Mitochondrial complex I deficiency is one of the most common defects in patients with mitochondrial disease. The deficiency results from a failure to assemble the enzyme properly, but the nature of the molecular chaperones that are necessary for this process in mammals have remained obscure.

In a new study appearing on October 3 in The Journal of Clinical Investigation, Eric Shoubridge and colleagues McGill University identify candidate proteins involved in complex I assembly, and show that one of the candidates, B17.2L, is an assembly factor. The authors identify a null mutation in a patient with a progressive encephalopathy, and show that the defect can be functionally complemented by expression of the wild-type cDNA in patient cells. (...)

National Human Genome Research Institute, Bethesda, MD USA
View the PDF of this article at:
the-jci.org/article.php?id=26625

Incidence of anti-brain antibodies in children with obsessive–compulsive disorder
British Journal of Psychiatry 2005;187:314-319
Method We examined 50 children with OCD for ABGA using enzyme-linked immunosorbent assay (ELISA) and western immunoblotting. The findings were compared with paediatric autoimmune (n=50), neurological (n=100) and streptococcal (n=40) controls.

Results The mean ABGA binding on ABGA binding on ELISA was elevated in the patient cohort compared with all control groups (P<0.005 in all comparisons). Western immunoblotting revealed positive antibody binding (as seen in Sydenham’s chorea) in 42% of the patient cohort compared with 2–10% of control groups (P<0.001 in all comparisons).

Conclusions Our findings support the hypothesis that central nervous system autoimmunity may have a role in a significant subgroup of cases of OCD. Further studyis required to examine whether the antibodies concerned are pathogenic.

- Ingen gener for aldring
forskning.no 9.9.2005
Det finnes ingen gener for aldring, mener professor Thomas Kirkwood. Trolig aldres vi mennesker og alle andre organismer fordi reparerings- og vedlikeholdssystemet i kroppen bryter sammen over tid.
Dette kom fram under Kirkwoods foredrag ”Det genetiske puslespillet bak aldring: Hvordan ser bitene ut, og hvordan passer de sammen”, som han holdt under genkonferansen ”Functional genomics and disease” som pågår i Oslo.

Ber genene om hjelp
Aftenposten 7.9.2005
Jakten på våre gener er over. Nå er det hva de betyr og hvordan de i samspill med hverandre og miljø fører til sykdom som er forskernes utfordringer. (...)

100 TRILLIONER CELLER
Menneskekroppen inneholder rundt 100 trillioner celler. I hver enkelt celle er det en cellekjerne som inneholder 23 kromosompar.

Hvert kromosom fra de 23 parene inneholder arvestoff fra far eller mor.

Kromosomene består av tettpakkede DNA-molekyler som til sammen utgjør det humane genom, altså våre gener.

Genene er de deler av DNA som inneholder instrukser eller er programmert for å produsere proteiner-kroppens byggestener.

Det første forsøket med genterapi startet i 1990. Nå er flere hundre forsøk med mange tusen pasienter gjennomført.

Oksidativt stress forkorter livet
Tidsskr Nor Lægeforen 2005; 125: 2329 (8.9.2005)
Oksidative skader på makromolekyler forkorter livslengden til invertebrater. En musestudie viser at dette også gjelder pattedyr.

Reaktive oksygenradikaler dannes sannsynligvis ved at elektroner unnslipper fra elektrontransportkjeden i mitokondrier. Oksygenradikalene skader andre makromolekyler i cellene og fører til redusert funksjon og forkortet livslengde. Siden oksygenradikalene produseres i mitokondriene, vil trolig størst skade på makromolekyler observeres der.

I en studie fra USA har teorien om oksidativt stress blitt studert i mus (1). Transgene musemodeller med overekspresjon av det antioksiderende enzymet katalase i mitokondrier, peroksisomer eller cellekjernen ble produsert. Det viste seg at hos mus med katalase i mitokondriene økte median og maksimal livslengde med rundt 20 %. Mus med katalase i peroksisomene hadde noe forlenget livslengde, mens mus med katalase i kjernen ikke hadde økt overlevelse.

Ikke så like likevel
Tidsskr Nor Lægeforen 2005; 125: 2333 (8.9.2005)
Mennesker har de samme genene, men arvematerialet ser ut til å være mer ulikt mellom individer enn tidligere antatt.

Arten menneske kan defineres på bakgrunn av de genene vi har i arvematerialet. Inntil nylig har vi trodd at to individer har 99,9 % identisk arvemateriale. Denne hypotesen ble svekket da to studier nylig viste at det finnes hundrevis av kopinummerpolymorfismer i arvematerialet (1). En kopinummerpolymorfisme defineres ved at et større område av DNA (vanligvis 100 kilobaser eller større) er repetert en eller flere ganger.

Study Reveals Mitochondrial Role in Aging
JAMA. 2005;294:672
Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.

Experiments that caused mice to quickly develop characteristics of premature aging reveal that mutations in mitochondrial DNA may play a key role in growing old.

For years, mitochondria have been linked to aging. In the new findings, researchers demonstrated that an accumulation of genetic mutations in mitochondria sets off a cascade of signals that causes programmed cell death, or apoptosis (Kujoth et al. Science. 2005;309:481-484). The result is loss of irreplaceable cells and progression of aging.

A normal mouse (left) and a mouse with mitochondrial DNA defects (right) are similar in age, but the mouse at right exhibits symptoms of aging, including graying, hair loss, and loss of muscle mass and spine strength. (Photo credit: Jeff Miller/University of Wisconsin-Madison)

All mitochondria have their own DNA, separate from DNA in the cell's nucleus. Researchers have known that mutations in mitochondrial DNA accumulate over time, but how these.

A normal mouse (left) and a mouse with mitochondrial DNA defects (right) are similar in age, but the mouse at right exhibits symptoms of aging, including graying, hair loss, and loss of muscle mass and spine strength. (Photo credit: Jeff Miller/University of Wisconsin-Madison.)

Using mitochondrial DNA as a biosensor of early cancer development
Editorial
British Journal of Cancer 200; 93:271-272.
Mitochondria can perform multiple cellular functions including energy production, cell proliferation and apoptosis. Each human cell contains hundreds to several thousand copies of the 16.5 kb human mitochondrial genome, which incidentally exhibits a maternal pattern of inheritance. This closed circular genome encodes 13 polypeptides of the respiratory chain complexes, as well as 22 transfer RNAs and two ribosomal RNAs used in mitochondrial protein synthesis. Compared to nuclear DNA, mitochondrial DNA (mtDNA) is highly susceptible to damage because it is not associated with protective histones, it is continually exposed to high levels of reactive oxygen species (ROS) generated by oxidative phosphorylation, and there is a limited capacity for mtDNA repair. The complete mtDNA sequence was determined in 1981 and resequenced in 1999. A growing collection of reported mtDNA mutations and rearrangements has been associated with muscle and neurodegenerative diseases (Birch-Machin, 2000).

Kokain, marihuana, kannabis (før: cannabis), lykkepiller og ecstasy

Marijuana linked to brain damage (Marijuana linket til hjerneskade)
Los Angeles Times 5.12.2005
Ugdommer som jevnlig røyker marihuana risikerer skade på en essensiell nervebane i hjernen assosiert med språkutvikling, og enkelte predisponert for schizofreni kan pådra seg sykdommen i ung alder, sa forskerne onsdag, også på møtet til Radiological Society of North America. (Adolescents who regularly smoke marijuana risk damaging a key brain pathway associated with language development, and some predisposed to schizophrenia may contract the illness early, researchers said Wednesday, also at the meeting of the Radiological Society of North America.)

Hjerneskanninger avslørte mikroskopiske uregelmessigheter i et område av hjernen som styrer høyere aspekter av språk og lyttefunksjoner hos ungdommer som er tunge marihuanarøykere. (Brain scans revealed microscopic abnormalities in a region of the brain that governs higher aspects of language and listening functions in adolescents who are heavy marijuana smokers.)

Liknende skade på buntene av fibrer, kalt arcuate fasciculus, som forbinder område for Broca i den venstre pannelapp og Wernicke i den venstre temporallappen ble funnet i hjernene til studerte marihuanarøykere og schizofrenikere. (Similar damage to the bundle of fibers, called the arcuate fasciculus, that connect Broca's area in the left frontal lobe and Wernicke's area in the left temporal lobe was found in the brains of marijuana smokers and schizophrenics studied.)

Marijuana Compound Spurs Brain Cell Growth (Marihuana-preparat ansporer vekst av hjerneceller)
forbes.com 13.10.2005

Antidepressants May Spur Brain Cell Growth (Antidepressiva kan anspore vekst av hjerneceller)
healthfinder.gov 27.12.2005

Antidepressiva påverkar tillväxt av nya hjärnceller
Läkemedelsvärlden 2003(9) (9.9.2003)

3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro. Mol Pharmacol. 2003 Jun;63(6):1223-9.

Cocaine and ecstasy cause DNA mutation: study
Reuters Health 5.12.2003
- Cocaine and ecstasy not only cause addiction and raise the risk of cancer but also provoke genetic mutations, Italian scientists said on Friday.
"Cocaine and ecstasy have proved to be more dangerous than we had imagined," said Giorgio Bronzetti, chief scientist at the National Center for Research's (CNR) biotechnology department.

"These drugs, on top of their toxicological effects, attack DNA provoking mutations and altering the hereditary material. This is very worrying for the effects it could have on future generations," he said.

Study: ecstasy, prozac fight cancer
sciencedaily.com 11.5.2005
BIRMINGHAM, England, May 11 (UPI) -- A University of Birmingham study suggests the popular rave drug ecstasy might be effective in treating cancer, the London Daily Mirror reported Wednesday.

(Anm: Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. J Clin Invest. 2005 Nov 1;115(11):3104-3116. Epub 2005 Oct 13.)

MPTP

The content of intracellular mitochondrial DNA is decreased by 1-methyl-4-phenylpyridinium ion (MPP+)
J Biol Chem 1997;272(15):9605-8
1-Methyl-4-phenylpyridinium ion (MPP+), an oxidative metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is considered to be directly responsible for MPTP-induced Parkinson's disease-like symptoms by inhibiting NADH-ubiquinone oxidoreductase (complex I) in the mitochondrial respiratory chain. Here we demonstrate that 25 microM MPP+ decreases the content of mitochondrial DNA to about one-third in HeLa S3 cells. On the contrary, 0.1 microM rotenone, which inhibits complex I to the same extent as 25 microM MPP+ in the cells, increases the content of mitochondrial DNA about 2-fold. Hence, the effect of MPP+ on mitochondrial DNA is not mediated by the inhibition of complex I. To examine the replication state of mitochondrial DNA, we measured the amount of nascent strands of mitochondrial DNA. The amount is decreased by MPP+ but increased by rotenone, suggesting that the replication of mitochondrial DNA is inhibited by MPP+. Because the proper amount of mitochondrial DNA is essential to maintain components of the respiratory chain, the decrease of mitochondrial DNA may play a role in the progression of MPTP-induced Parkinson's disease-like symptoms caused by the mitochondrial respiratory failure. (1-Methyl-4-phenylpyridinium ion (MPP+), an oxidative metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is considered to be directly responsible for MPTP-induced Parkinson's disease-like symptoms by inhibiting NADH-ubiquinone oxidoreductase (complex I) in the mitochondrial respiratory chain. Here we demonstrate that 25 microM MPP+ decreases the content of mitochondrial DNA to about one-third in HeLa S3 cells. On the contrary, 0.1 microM rotenone, which inhibits complex I to the same extent as 25 microM MPP+ in the cells, increases the content of mitochondrial DNA about 2-fold. Hence, the effect of MPP+ on mitochondrial DNA is not mediated by the inhibition of complex I. To examine the replication state of mitochondrial DNA, we measured the amount of nascent strands of mitochondrial DNA. The amount is decreased by MPP+ but increased by rotenone, suggesting that the replication of mitochondrial DNA is inhibited by MPP+. Because the proper amount of mitochondrial DNA is essential to maintain components of the respiratory chain, the decrease of mitochondrial DNA may play a role in the progression of MPTP-induced Parkinson's disease-like symptoms caused by the mitochondrial respiratory failure.)

1-Methyl-4-phenylpyridinium ion (MPP+) selectively inhibits the replication of mitochondrial DNA
Eur J Biochem 1999;259(1-2):412-8
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine is known to cause Parkinsonism in its neurotoxic form, 1-methyl-4-phenylpyridinium ion (MPP+). We have previously reported that MPP+ decreases the content of mitochondrial DNA (mtDNA) independently of the inhibition of complex I in human cells [Miyako, K., Kai, Y., Irie, T., Takeshige, K., and Kang, D. (1997) J. Biol. Chem. 272, 9605-9608]. Here we study the mechanism causing the decrease in mtDNA. MPP+ inhibits the incorporation of 5-bromo-2'-deoxyuridine into mtDNA but not into nuclear DNA, indicating that MPP+ inhibits the replication of mtDNA but not that of the nuclear genome. The replication of mtDNA is initiated by the synthesis of the heavy strand switched from the transcription of the light strand. MPP+ decreases the nascent heavy strands per mtDNA and increases the transcript of the ND6 gene, encoded on light strand, per mtDNA. The amount of mitochondrial transcription factor A is not decreased. These data suggest that the transcription is not inhibited and therefore the transition from transcription to replication of mtDNA is lowered in the MPP+-treated cells. Electron microscopy shows that the number of mitochondria is not decreased in the MPP+-treated cells, suggesting that MPP+ does not affect the overall biogenesis of mitochondria. Thus, MPP+ selectively inhibits the replication of mtDNA. (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine is known to cause Parkinsonism in its neurotoxic form, 1-methyl-4-phenylpyridinium ion (MPP+). We have previously reported that MPP+ decreases the content of mitochondrial DNA (mtDNA) independently of the inhibition of complex I in human cells [Miyako, K., Kai, Y., Irie, T., Takeshige, K., and Kang, D. (1997) J. Biol. Chem. 272, 9605-9608]. Here we study the mechanism causing the decrease in mtDNA. MPP+ inhibits the incorporation of 5-bromo-2'-deoxyuridine into mtDNA but not into nuclear DNA, indicating that MPP+ inhibits the replication of mtDNA but not that of the nuclear genome. The replication of mtDNA is initiated by the synthesis of the heavy strand switched from the transcription of the light strand. MPP+ decreases the nascent heavy strands per mtDNA and increases the transcript of the ND6 gene, encoded on light strand, per mtDNA. The amount of mitochondrial transcription factor A is not decreased. These data suggest that the transcription is not inhibited and therefore the transition from transcription to replication of mtDNA is lowered in the MPP+-treated cells. Electron microscopy shows that the number of mitochondria is not decreased in the MPP+-treated cells, suggesting that MPP+ does not affect the overall biogenesis of mitochondria. Thus, MPP+ selectively inhibits the replication of mtDNA.)

Bivirkninger psykofarmaka (complex 1)

Mitochondrial Complex I Activity and Oxidative Damage to Mitochondrial Proteins in the Prefrontal Cortex of Patients With Bipolar Disorder
Arch Gen Psychiatry. 2010;67(4):360-368 (April)
Context Accumulating evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of bipolar disorder and schizophrenia. It remains unclear whether mitochondrial dysfunction, specifically complex I impairment, is associated with increased oxidative damage and, if so, whether this relationship is specific to bipolar disorder. (...)

Conclusions Impairment of complex I may be associated with increased protein oxidation and nitration in the prefrontal cortex of patients with bipolar disorder. Therefore, complex I activity and mitochondrial dysfunction may be potential therapeutic targets for bipolar disorder. (...)

Tardive dyskinesia and substrates of energy metabolism in CSF
Am J Psychiatry 1995;152:1730-1736
(...) KONKLUSJONER: Disse resultater er overensstemmende med en modell som linker nevropleptikainduserte sideeffekte til svekkelse av mitokondriell enegimetabolisme, mulig mediert ved hemning av complex 1. (CONCLUSIONS: These results are consistent with a model linking neuroleptic-induced neurological side effects with impairment of mitochondrial energy metabolism, possibly mediated by inhibition of complex 1 of the electron transport chain.)

Changes in the amount and distribution of neuronal alkaline and acid phosphatase after chronic exposure of cultures of cingulate cortex to antidepressant drugs
J Neural Transm Gen Sect 1992;90:67-80
Enzyme histochemistry was used to examine alkaline and acid phosphatases in cultures of embryonic rat cingulate cortex after 14 days exposure in vitro to two tricyclic antidepressants (amitriptyline and desipramine) and two non-tricyclic antidepressants (mianserin and citalopram). An increased amount of acid phosphatase reaction product was observed in lysosomes of neurons in cultures treated chronically with the non-tricyclic antidepressants, mianserin or citalopram. More strikingly, reaction product was also present in the inner lamellae of the Golgi apparatus after this treatment, but never in controls. These observations suggest that non-tricyclic antidepressants significantly increase the rate of degradative processes in cingulate neurons. In cultures, treated chronically with desipramine or amitriptyline, pre- and postsynaptic membranes contained heavy deposits of alkaline phosphatase reaction product, whereas in control cultures not exposed to these drugs the corresponding membranes were entirely devoid of reaction product. An increase in the amount of alkaline phosphatase reaction product was also observed on the plasma membranes of neuronal cell bodies. These observations suggest that chronic exposure to antidepressants may influence transmembrane transport in cingulate neurons. (...)

Inhibition of complex 1 by neuroleptic in normal human brain cortex parallels the extrapyramidals toxicity of neuroleptics
Moll Cell biochem 1997;174:255-259
There is increasing evidence that a defect of the mitochondrial respiratory chain is implicated in the development of Parkinson disease. Decreased complex I activity of the mitochondrial respiratory chain has been reported in platelets, muscle, and brain of patients with Parkinson disease. Extrapyramidal symptoms (e.g. parkinsonism and dystonic reactions) are major limiting side effects of neuroleptics. Experimental evidence suggests that neuroleptics inhibit complex I in rat brain. There has not been a study of the effects of neuroleptics in human tissue, however. (...)

Våre data støtter hypotesen om at nevroleptikainduserte ekstrapyramidale sideeffekter kan skyldes midlenes hemming av den mitokondrielle respirasjonskjeden. (Our data support the hypothesis that neuroleptic-induced extrapyramidal side effects may be due to inhibition of the mitochondrial respiratory chain.)

(Anm: dystonia; dystoni; endring i muskulaturens spenningstilstand, ofte i form av ufrivillige muskelsammentrekninger (f.eks. i nakkemuskulaturen og svelgmuskulaturen. Dystoni kan være symptom ved indremedisinske og nevrologiske sykdommer, men kan også opptre som bivirkning av legemidler som blokkerer signalsubstansen dopamin. Akutte dystonier sees hos yngre menn noen dager etter at vedkommende har begynt på relativt høye doser med nevroleptika. (...) Ved akutte dystonier på grunn av legemidler er behandlingen tilførsel av antiparkinsonmidler. Kilde: Store norske leksikon.)

Neuroleptic-induced mitochondrial enzyme alterations in the rat brain
Pharmacol Exp Ther 1997;280:261-7
For years, it has been known that neuroleptics have the capacity to interfere with the mitochondrial respiratory chain in vitro. We report that haloperidol and fluphenazine, classical neuroleptics, cause a generalized reduction in the activity of NADH: ubiquinone oxidoreductase (complex I) in the rat brain in vivo, an effect that was not observed with the atypical neuroleptic, clozapine. MPTP, which bears significant structural similarities with haloperidol, also demonstrated a significant reduction in complex I activity after low-dose, chronic administration. Interestingly, an increase in the activity of cytochrome-c oxidase (complex IV), probably reflecting enhanced functional neuronal activity, was observed in the frontal cortex of all chronically treated animals, an effect that is unlikely to result from compensation for the inhibition of complex I. Results suggest that previous findings, in which a reduction in the activity of cytochrome-c oxidase was observed in postmortem brain samples from schizophrenics, are not dependent on treatment with neuroleptics. (...)

Neuroleptic medications inhibit complex 1 electron transport chain
Ann Neurol 1993;33:512-517
Pasienter behandlet med nevropleptika har signifikant redusert aktivitet av complex 1 i blodplater på lignende måte som observert for ekstrapyramidale sideeffekter ved Parkinsons sykdom. (Neuroleptic treated patients have significant depression of platelet complex I activity similar to that seen in idiopathic Parkinson's disease. Complex I inhibition may be associated with the extrapyramidal side effects of these drugs.)

The effects of various antidepressant drugs on the fine-structure of neurons of the cingulate cortex in culture
Neuroscience 1990;37:685-92
For mianserin- (Tolvon) og citalopram- (Cipramil) behandlede kulturer, fikk synaptiske "specializations" økt lengde, og det ble observert en opphopning av mitokondrier "at the base of neuritis". Våre resultater indikerte at langtidsbruk av antidepressiva førte til en signifikant endring i den intracellulære struktur, samt endringer i synaptisk ultrastruktur. (In mianserin- and citalopram-treated cultures, synaptic specializations were increased in length, and aggregates of mitochondria at the base of neurites were observed. Our results indicate that long-term exposure to antidepressant drugs results in significant changes in intracellular structure, including changes in synaptic ultrastructure.)

Late onset familial dystonia: could mitochondrial deficits induce a diffuse lesioning process of the whole basal ganglia system?
J Neurol Neurosurg Psychiatry 1997;63:196-203
BACKGROUND: Striatal necrosis has been related to various clinical syndromes, with acute or chronic progression, and juvenile or late occurrence, but the most common type is Leigh's encephalopathy. METHODS: Between 1967 and 1995, six out of seven related patients with chronic familial dystonia were examined. MRIs were performed in four, between 1992-1994. The seven members, affected over three generations, were the father, three daughters (one surviving), and three surviving grandsons. (...)

CONCLUSION: This familial dystonia of chronic progression may be related to basal ganglia necrosis or gliosis, associated with alterations in the respiratory chain. These metabolic alterations probably play a part in the pathophysiology of these unusual brain lesions. (...)

Hypothyroidism leads to a decreased expression of mitochondrial F0F1-ATP synthase in rat liver
J Bioenerg Biomembr. 1998 Jun;30(3):269-76
I levermitokondrier isolert fra hypothyreoide rotter, er mengden av ATP syntese lavere enn i mitokondrier hos nomale rotter. (...)

Resultatene som ble oppnådd indikerer at hypothyreoidisme fører til redusert F0F1-ATP syntese kompleks i lever og bidrar til redusert effektivitet av oksydativ fosforilering (oxidative phosphorylation).

(Anm: Hypothyroidism leads to a decreased expression of mitochondrial F0F1-ATP synthase in rat liver. (J Bioenerg Biomembr 1998;30:269-76). (In liver mitochondria isolated from hypothyroid rats, the rate of ATP synthesis is lower than in mitochondria from normal rats. (...) The results obtained indicate that hypothyroidism leads to a decreased expression of F0F1-ATP synthase complex in liver mitochondria and this contributes to the decrease of the efficiency of oxidative phosphorylation.)

Mitokondrier versus Parkinsons sykdom

Study: Antioxidant slows Parkinson's
usatoday.com 14.10.2002
A large dose of the dietary supplement coenzyme Q10 appears to slow the progression of disability caused by Parkinson's disease, according to a study out today. (A large dose of the dietary supplement coenzyme Q10 appears to slow the progression of disability caused by Parkinson's disease, according to a study out today.)

Parkinson's disease is a degenerative brain disorder that leads to tremors, slow movement and stiff muscles. It affects about 1% of Americans older than 65, although younger people also can develop the disease. Former U.S. attorney general Janet Reno, the Rev. Billy Graham and actor Michael J. Fox all have Parkinson's disease. (Parkinson's disease is a degenerative brain disorder that leads to tremors, slow movement and stiff muscles. It affects about 1% of Americans older than 65, although younger people also can develop the disease. Former U.S. attorney general Janet Reno, the Rev. Billy Graham and actor Michael J. Fox all have Parkinson's disease.)

While some drugs, such as levodopa, can relieve symptoms, no treatment has been shown to slow the progression of disability. (While some drugs, such as levodopa, can relieve symptoms, no treatment has been shown to slow the progression of disability.)

The decision to test coenzyme Q10 stems from earlier work by Shults and others. They found that Parkinson's disease patients have reduced levels of coenzyme Q10 in the mitochondria (a component of cells) of their platelets. (The decision to test coenzyme Q10 stems from earlier work by Shults and others. They found that Parkinson's disease patients have reduced levels of coenzyme Q10 in the mitochondria (a component of cells) of their platelets.)

Effects of coenzyme q10 in early Parkinson disease: evidence of slowing of the functional decline
Arch Neurol 2002;59:1541-50
CONCLUSIONS: Coenzyme Q(10) was safe and well tolerated at dosages of up to 1200 mg/d. Less disability developed in subjects assigned to coenzyme Q(10) than in those assigned to placebo, and the benefit was greatest in subjects receiving the highest dosage. Coenzyme Q(10) appears to slow the progressive deterioration of function in PD, but these results need to be confirmed in a larger study. (CONCLUSIONS: Coenzyme Q(10) was safe and well tolerated at dosages of up to 1200 mg/d. Less disability developed in subjects assigned to coenzyme Q(10) than in those assigned to placebo, and the benefit was greatest in subjects receiving the highest dosage. Coenzyme Q(10) appears to slow the progressive deterioration of function in PD, but these results need to be confirmed in a larger study.)

A possible role of coenzyme Q10 in the etiology and treatment of Parkinson's disease
Biofactors 1999;9:267-72
Parkinson's disease (PD) is a degenerative neurological disorder. Recent studies have demonstrated reduced activity of complex I of the electron transport chain in brain and platelets from patients with PD. Platelet mitochondria from parkinsonian patients were found to have lower levels of coenzyme Q10 (CoQ10) than mitochondria from age/sex-matched controls. There was a strong correlation between the levels of CoQ10 and the activities of complexes I and II/III. Oral CoQ10 was found to protect the nigrostriatal dopaminergic system in one-year-old mice treated with MPTP, a toxin injurious to the nigrostriatal dopaminergic system. We further found that oral CoQ10 was well absorbed in parkinsonian patients and caused a trend toward increased complex I activity. These data suggest that CoQ10 may play a role in cellular dysfunction found in PD and may be a potential protective agent for parkinsonian patients. (Parkinson's disease (PD) is a degenerative neurological disorder. Recent studies have demonstrated reduced activity of complex I of the electron transport chain in brain and platelets from patients with PD. Platelet mitochondria from parkinsonian patients were found to have lower levels of coenzyme Q10 (CoQ10) than mitochondria from age/sex-matched controls. There was a strong correlation between the levels of CoQ10 and the activities of complexes I and II/III. Oral CoQ10 was found to protect the nigrostriatal dopaminergic system in one-year-old mice treated with MPTP, a toxin injurious to the nigrostriatal dopaminergic system. We further found that oral CoQ10 was well absorbed in parkinsonian patients and caused a trend toward increased complex I activity. These data suggest that CoQ10 may play a role in cellular dysfunction found in PD and may be a potential protective agent for parkinsonian patients.)

Mitokondrier og dystonia

Mitochondria and dystonia: the movement disorder connection?
Proc Natl Acad Sci U S A 1999;96:1817-9

Spasmer i nakke (torticollis) hos nyfødte etter inntak av SSRI-er

Study Contradicts USA Warning That An Antidepressant Can Cause Congenital Abnormalities
medicalnewstoday.com 20.6.2006
A study carried out by German researchers has failed to show that a popular antidepressant, paroxetine®, causes congenital abnormalities if taken by pregnant women, the 22nd annual conference of the European Society of Human Reproduction and Embryology heard. (...)

In contrast, the research carried out by Dr Paulus and his colleagues was a prospective follow-up study that collected data on pregnancy outcomes after medication with paroxetine® in 119 women between 1990 and 2005. "Our national Teratology Information Service (TIS) was contacted by physicians and patients after exposure to paroxetine® in the first trimester of pregnancy. We compared the results with a control group of 645 women over the same period of time, who had not been exposed, or not severely exposed, to the drug.

"We found that the rate of congenital abnormalities was not increased after using paroxetine® in early pregnancy. Three abnormalities were reported after exposure to paroxetine®: club feet after exposure throughout pregnancy, a large port wine mark after exposure up to the seventh week, and spastic torticollis (painful spasms of the neck muscles) after exposure in the first twelve weeks. However, in the non-paroxetine® group there was a similar rate of abnormalities, with 25 out of 557 babies affected." (...)

(Anm: Den nevnte studie er for liten til å si noe om sikkerheten til legemidlet Seroxat, men det er interessant å registrere at også nyfødte (i likhet med voksne) får alvorlige smertefulle spasmer i bl.a. nakkemuskler (torticollis) grunnet inntak av nevnte legemiddel.

(Anm: torticollis; skeiv hals; vridd eller skakk hals pga trekkingar eller skrumping i halsmusklane; jf dystoni EN torticollis ET [lat. tortus vridd + collum hals] Kilde: Norsk medisinsk ordbok.)

(Anm: dystonia; dystoni; endring i muskulaturens spenningstilstand, ofte i form av ufrivillige muskelsammentrekninger (f.eks. i nakkemuskulaturen og svelgmuskulaturen. Dystoni kan være symptom ved indremedisinske og nevrologiske sykdommer, men kan også opptre som bivirkning av legemidler som blokkerer signalsubstansen dopamin. Akutte dystonier sees hos yngre menn noen dager etter at vedkommende har begynt på relativt høye doser med nevroleptika. (...) Ved akutte dystonier på grunn av legemidler er behandlingen tilførsel av antiparkinsonmidler. Kilde: Store norske leksikon.)

Eksponering for plantevernmidler (pesticider) linket til Parkinsons sykdom

Pesticide Exposure and Parkinson's Rate Linked
latimes.com 1.7.2006
People with long-term low-level exposure to pesticides have a 70% higher incidence of Parkinson's disease than people who have not been exposed much to bug sprays, U.S. researchers have reported.

Such people include farmers, ranchers and fishermen, the researchers report in the July issue of Annals of Neurology. Their study supports previous research that links pesticides with Parkinson's, which is caused by the destruction of key brain cells, the team at the Harvard School of Public Health said (...)

Studie linker luftforurensende stoffer til autisme

Study Links Air Pollutants With Autism
latimes.com 23.6.2006
Bay Area children with the disorder are 50% likelier to be from areas high in several toxic substances. Scientists say more research is needed.

Children with autism disorders in the San Francisco Bay Area were 50% more likely to be born in neighborhoods with high amounts of several toxic air contaminants, particularly mercury, according to a first-of-its-kind study by the California Department of Health Services.

The new findings, which surprised the researchers, suggest that a mother's exposure to industrial air pollutants while pregnant might increase her child's risk of autism, a neurological condition increasingly diagnosed in the last 10 years.

But the scientists cautioned that the link they found in the Bay Area is uncertain and that more definitive evidence would be needed before concluding that mercury or any other pollutant could trigger autism. (...)

- p53 Regulates Mitochondrial Respiration

Har funnet «missing link» i cellenes kreftforsvar
dagbladet.no 1.2.2009
- Viktig for behandling og diagnose.

(Dagbladet.no): Forskere sier de nå har funnet en «missing link» i måten kroppens celler beskytter seg mot kreft, melder BBC.

De har avslørt hvordan cellene skrur av og på et gen, kalt p53. Dette genet kan hindre utvikling av svulster.

Studien er publisert i det anerkjente legetidsskriftet Genes & Development. Forskere fra Singapor og Dundee-universitetet står bak de oppsiktsvekkende funnene. (...)

p53 Regulates Mitochondrial Respiration
sciencemag.org (May 25, 2006)
The energy that sustains cancer cells is derived preferentially from glycolysis. This metabolic change, the Warburg effect, was one of the first recognized alterations in cancer cells conferring a survival advantage. Here, we show that p53, one of the most frequently mutated genes in cancers, modulates the balance between the utilization of respiratory and glycolytic pathways. We identify Synthesis of Cytochrome c Oxidase 2 (SCO2) as the downstream mediator of this effect in mice and human cancer cell lines. SCO2 is critical for regulating the cytochrome c oxidase (COX) complex, the major site of oxygen utilization in the eukaryotic cell. Disruption of the SCO2 gene in human cancer cells with wild-type p53 recapitulated the metabolic switch towards glycolysis that is exhibited by p53-deficient cells. That SCO2 couples p53 to mitochondrial respiration provides a possible explanation for the Warburg effect and offers new clues as to how p53 might affect aging and metabolism. (...)

Gene-regulating enzyme is also a target for anti-depressive drugs

Gene-regulating enzyme is also a target for anti-depressive drugs
hindu.com 25.6.2006
Anti-cancer possibilities seen for certain monoamine oxidase inhibitors
This press release issued by EurekAlert says that in 2005, professor Ramin Shiekhattar, Ph.D., at The Wistar Institute and his colleagues reported details about an enzyme involved in appropriately repressing sets of neuronal genes in non-neuronal cells.

At the time, the scientists noted that the enzyme appeared to fit into the same extended enzyme family that includes monoamine oxidases, psychoactive enzymes that oxidize dopamine and norepinephrin. Inhibitors of these enzymes have long been used to treat depression, certain other psychiatric and emotional disorders, and Parkinson's disease.

Now, in a study published online today in the June 26 issue of Chemistry & Biology, Shiekhattar and his team show that the enzyme is itself a target for certain monoamine oxidase inhibitors used to treat depression. One member of this family of drugs in particular, called tranylcypromine (brand name Parnate®, manufactured by GlaxoSmithKline), was seen to inhibit the enzyme most strongly. The findings suggest that these anti-depressive drugs may have additional applications in other medically relevant areas.

Scientists Find Clue to Cell Suicides

Scientists Find Clue to Cell Suicides
english.donga.com 2.10.2006
A new mechanism for cells killing themselves was found by an international joint research group, which a Korean scientist is participating in.

Professor Jeong Seon-Yong (40) of the Department of Medical Genetics at Ajou University’s School of Medicine said on October 1, “We found that proteins called “Bax” and “Bak” control the process of apoptosis, or cellular self-deconstruction.”

This new discovery will hopefully provide substantial aid to the research of the causes of diseases in which cells self-deconstruct, such as cancer and dementia.

In a healthy cell, bean-shaped mitochondria create the energy required to sustain life by repeating the process of making contact and then moving apart. If something goes wrong in this process, the results are cancer, dementia, or rapid aging.

The research group observed mitochondria with a laser-scanning microscope after removing the Bax and Bak from human and mouse cells. The results showed mitochondria failing to come into contact with each other.

Professor Jeong said, “Bax and Bak were known only as proteins inducing apoptosis. This is the first time they have been proved to have the function of connecting mitochondria.”

A cell relinquishes its life if it becomes damaged to the point where recovery is impossible. In the process of this self-deconstruction, mitochondria no longer come into contact.

It is a probable induction that apoptosis is caused by Bax and Bak failing to connect mitochondria. These results were published in the October 1 online edition of “Nature.”

- Steroider forårsaker "katastrofal" hjerneskade (Steroids cause "catastrophic" brain damage)

Steroids cause "catastrophic" brain damage (Steroider forårsaker "katastrofal" hjerneskade)
netdoctor.co.uk 3.10.2006
Continued use of steroids by people wishing to develop their muscles could lead to a "catastrophic loss of brain cells", a new study says.

Researchers from Yale School of Medicine claim that the damage is caused by the steroids' high-testosterone levels.

They write that the drugs could cause hyperexcitability and lead to highly-aggressive natures, as well as suicidal tendencies. (...)

Today's study says that the testosterone found within steroids induces changes within brains at a cellular level, thus causing the severe shifts in behaviour, mood and memory. (...) (Dagens studie viser at testosteron funnet i steroider induserer forandringer i hjernen på cellulert nivå, og forårsaker dermed endringer av atferd, humør og hukommelse)

Rapporten konkluderer at langvarig steroidbruk vil kunne føre til uastabile membran og til slutt DNA-fragmentering (DNA-skade) (...) (The report concludes that prolonged steroid use could lead to membrane instability and ultimately DNA fragmentation.)

(Anm: Elevated testosterone induces apoptosis in neuronal cells. J Biol Chem. 2006 Sep 1;281(35):25492-501. Epub 2006 Jun 27.)

- Depresjon øker faren for Alzheimer?

- Depresjon øker faren for Alzheimer
vg.no 8.4.2008
(VG Nett) Mennesker som har slitt med depresjoner er mer utsatt for å utvikle Alzheimer, hevder to nye forskningsstudier. (...)

Den nederlandske undersøkelsen var relativt liten, 486 personer ble fulgt over 6 år. 33 av disse utviklet Alzheimer. Undersøkelsen viste at de personene som deltok i undersøkelsen hadde 2,5 gang så stor mulighet til å få Alzheimer dersom de slet med depresjoner. De som hadde depresjoner før de fylte 60 år, hadde fire ganger så stor sjanse for å utvikle Alzheimer.

En amerikansk undersøkelse fulgte 900 katolske prester over 13 år. I dette utvalget utviklet 190 Alzheimer. Også denne undersøkelsen konkluderte med at de som viste symptomer på depresjon tidlig i undersøkelsen hadde større sannsynlighet for å utvikle Alzheimer.

Ingen av undersøkelsene vil konkludere at det er en depresjon er en årsak til Alzheimer, men mener dette bør utredes videre. (...)

(Anm: Change in Depressive Symptoms During the Prodromal Phase of Alzheimer Disease. Arch Gen Psychiatry. 2008;65(4):439-445.

History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease. NEUROLOGY 2008;70:1258-1264.)

"Mitokodriell autisme"

NEW STUDY - "Mitochondrial Autism" is Real; Vaccine Triggers Cannot Be Ruled Out (NY STUDIE: - "Mitokondriell autisme" er reell; Vaksinetriggere kan ikke utelukkes)
huffingtonpost.com 28.11.2008
The December 1st issue of Time Magazine carries a special section on "The Year in Medicine," which mentions the case of Hannah Poling, the young girl with autism who received compensation from the federal vaccine injury program. Like many news accounts back then, Time has called the case "rare," because it involved an underlying dysfunction of Hannah's mitochondria, the little powerhouses within each cell that produce energy.

The widespread misconception that Hannah's case was "unique," and without any bearing on other autism cases, was promulgated by opinion leaders such as CDC Director Julie Gerberding and the newly rich vaccine inventor Dr. Paul Offit, (who told Newsweek that his share of the royalties from the vaccine was "like winning the lottery.")

But on Wednesday, a new chart-review study was published showing that "mitochondrial autism" is not rare at all. (...)

(Anm: Vaksiner (mintankesmie.no). (mintankesmie.no).)

The Next Vaccine-Autism Newsmaker Not Isolated, Not Unusual
huffingtonpost.com 27.4.2008
In February, I leaked news of the Federal government's admission that vaccines had triggered autism in a little girl named Hannah Poling. The stunning revelation, though still reverberating around the world, was roundly downplayed by US officials, who insisted that Hannah had an extremely rare, genetic case of "aggravated" mitochondrial disorder, with zero bearing on other autism cases. (...)

That theory, which applies to Hannah as well, maintains that children with dysfunctional mitochondria (the little batteries within each cell that convert food into energy) are susceptible to autistic regression, triggered by a vaccine-induced overtaxing of the immune system. (...)

A new, additional theory of causation is about to be introduced in Vaccine Court: Vaccines can trigger a chain of events in children with mitochondrial dysfunction that causes autism. (...)

Some estimates of mitochondrial dysfunction in children with autism range as high as 20%-30%. But among the regressive subset of cases (virtually all of the claims in Vaccine Court) up to half of the children might show signs of it. (...)

Deal in an Autism Case Fuels Debate on Vaccine (Avtale i autismesak gir næring til ny debatt om vaksine)
nytimes.com 8.3.2008
WASHINGTON — Study after study has failed to show any link between vaccines and autism, but many parents of autistic children remain unconvinced. For the skeptics, the case of 9-year-old Hannah Poling shows that they have been right along.

The government has conceded that vaccines may have hurt Hannah, and it has agreed to pay her family for her care. Advocates say the settlement — reached last fall in a federal compensation court for people injured by vaccines, but disclosed only in recent days — is a long-overdue government recognition that vaccinations can cause autism.

“This decision gives people significant reason to be cautious about vaccinating their children,” John Gilmore, executive director of the group Autism United, said Friday.

Mr. Gilmore has filed his own claim that his son became autistic as a result of vaccinations.

Government officials say they have made no such concession. (...)

Diverse artikler

Mitochondria and cardiovascular aging
Circ Res. 2012 Apr 13;110(8):1109-24.
Abstract Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and in cardiovascular aging. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and biogenesis as well as the crosstalk between mitochondria and cellular signaling in cardiac and vascular aging. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans (left ventricular hypertrophy, fibrosis and diastolic dysfunction), while the phenotype of vascular aging include endothelial dysfunction, reduced vascular elasticity, and chronic vascular inflammation. Both cardiac and vascular aging involve neurohormonal signaling (eg, renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics, and exercise training. (...)

Brain rust: Recent discoveries on the role of oxidative stress in neurodegenerative diseases
Nutr Neurosci. 2012 Apr 3. [Epub ahead of print]
Abstract Oxidative stress (OS) and damages due to excessive reactive oxygen species (ROS) are common causes of injuries to cells and organisms. The prevalence of neurodegenerative diseases (ND) increases with aging and much of the research involving ROS and OS has emerged from works in this field. This text reviews some recent published articles about the role of OS in ND. Since there are many reviews in this field, the focus was centered in articles published recently. The Scientific Journals Directory supported by the Brazilian Ministry of Education Office for the Coordination of Higher Educational Personnel Improvement (CAPES) was used to search, download, and review articles. The search engine looked for the terms 'oxidative stress AND neurodegenerative diseases AND nutrition' in 10 different scientific collections. Biochemical markers for ND lack sensitivity or specificity for diagnosis or for tracking response to therapy today. OS has an intimate connection with ND, albeit low levels of ROS seem to protect the brain. Deleterious changes in mitochondria, OS, calcium, glucocorticoids, inflammation, trace metals, insulin, cell cycle, protein aggregation, and hundreds to thousands of genes occur in ND. The interaction of genes with their environment, may explain ND. Although OS has received much attention over the years, which increased the number of scientific works on antioxidant interventions, no one knows how to stop or delay ND at present. Interventions in vitro, in vivo, and in humans will continue to contribute for a better understanding of these pathologies. (...)

Lundbeckfonden giver 10 mio kr til forskning i cellers pumpeværk
medwatch.dk 14.2.2012
Hvis man forstår cellers membranpumper til bunds, kan det også være nøglen til at forstå adskillige neurotiske lidelser. Lundbeckfonden har givet en 34-årig forsker fra Syddansk Universitet 10 mio. kr. til at fordybe sig i livets pumpeværk.

Den 34-årige forsker Himanshu Khandelia fra Syddansk Universitet har modtaget et Junior Group Leader Fellowship på 10 mio. kr. fra Lundbeckfonden.

Med den bevilling i ryggen, forsøger forskeren nu at finde frem til, hvad der går galt, når cellers membranpumper ikke virker. Himanshu Khandelia prøver at forstå fejl i pumpeværket helt ned på det molekylære niveau, skriver Dagens Medicin.

Himanshu Khandelia er uddannet ved University of Minnesota i USA, hvilket ifølge Dagens Medicin har gjort ham til en førende ekspert inden for molekylær modellering og simulering.

Ved at løse mysterier og øge sin viden om defekte og fungerende membranpumper kan man øge kendskabet til neurologiske lidelser. Derudover kan ny viden også gøre os klogere på, hvordan antibiotika-resistente bakterier bliver multiresistente. Området kan hjælpe mange led inden for lægemiddelforskningen på vej, fx med potentielle anvendelsesmuligheder fra udvikling af biosensorer til batterier i nano-format. (...)

Lundbeckfonden giver 10 mio. kr. til forskning i livets pumpeværk
dagensmedicin.dk 13.2.2012
Den 34-årige forsker Himanshu Khandelia fra Syddansk Universitet har modtaget et Junior Group Leader Fellowship på 10 mio. kr. fra Lundbeckfonden.

Menneskets krop befinder sig i en konstant kamp for at holde balancen. Ikke blot når vi cykler eller går på line. Hver enkelt celle i vores krop balancerer konstant via utallige biokemiske processer.

Himanshu Khandelia fra Syddansk Universitet arbejder med de helt centrale dele af kroppens balance – membranpumperne. Når de svigter, kan det have fatale konsekvenser – ikke blot for den enkelte celle, men for hele kroppen. Blandt andet ved man, at visse hjernelidelser skyldes små fejl i bestemt cellers ionpumper.

Med en bevilling på 10 mio. kroner fra Lundbeckfonden i ryggen, forsøger Himanshu Khandelia nu at finde frem til, hvad der går galt, når pumperne ikke virker. Himanshu Khandelia prøver at forstå disse fejl helt ned på det molekylære niveau.

Via bevillingen kan Himanshu Khandelia opbygge en forskergruppe, der har sin egen helt unikke kombination af teknisk kunnen og dyb indsigt i grundlæggende fysik og kemi.

Selv er han uddannet ved USAs absolut førende universitet inden for kemiteknik - University of Minnesota. Det har gjort ham til en førende ekspert inden for molekylær modellering og simulering. Nu kommer Danmark til at nyde godt af hans viden.

Udover at øge kendskabet til neurologiske lidelser, kan den nye viden om membranpumpernes funktion fx også gøre os klogere på, hvordan antibiotika-resistente bakterier bliver multiresistente. (...)

Masserer genene
aftenposten.no 10.2.2012
Nå har forskere funnet ut hvorfor massasje lindrer verkende muskler: Massasjen setter i gang gener som hjelper musklene i å helbredes og stopper gener knyttet til betennelse. I en studie hvor forskere undersøkte vev av masserte lår, fant de større grad av cellereparasjon enn i ikke-masserte lår og mer av gener som stimulerer mitokondriene, de deler av cellene som forbrenner energi, til å formere seg. Altså kan massasje ordineres ved siden av betennelsesdempende medikamenter mot verkende og betente muskler, skriver Science Translational Medicine. (...)

Scientists are to investigate “three parent IVF” for preventing mitochondrial diseases
BMJ 2012;344:e540 (20 January)
A pioneering research laboratory has been awarded £4.4m (€5.3m; $6.8m) to look into the role of a modified type of in vitro fertilisation (IVF) involving three adults to prevent the inheritance of mitochondrial diseases.

Mark Walport, director of the Wellcome Trust, which made the grant, said that “mitochondrial diseases can be devastating for sufferers and their families.” He added that although science had made great progress in uncovering the nature of these diseases, “treatment hasn’t kept pace.” (...)

Linking functional decline of telomeres, mitochondria and stem cells during ageing
Nature 464, 520-528 (25 March 2010) | doi:10.1038/nature08982; Published online 24 March 2010
Abstract The study of human genetic disorders and mutant mouse models has provided evidence that genome maintenance mechanisms, DNA damage signalling and metabolic regulation cooperate to drive the ageing process. In particular, age-associated telomere damage, diminution of telomere 'capping' function and associated p53 activation have emerged as prime instigators of a functional decline of tissue stem cells and of mitochondrial dysfunction that adversely affect renewal and bioenergetic support in diverse tissues. Constructing a model of how telomeres, stem cells and mitochondria interact with key molecules governing genome integrity, 'stemness' and metabolism provides a framework for how diverse factors contribute to ageing and age-related disorders.

Medical advances over the past century have produced a near doubling of human life expectancy in industrialized countries. This longevity boom — due primarily to improved neonatal care, to prevention and treatment of infections and to interventions for cardiovascular and endocrine diseases — is expected to lead to a population of 1.2 billion individuals aged 60 years or older by the year 2025. For medical technology to have a meaningful impact on the continued health and well-being of this ageing population, there is an increasingly urgent need for a more complete understanding of the molecular pathways and biological processes underlying ageing and age-related disorders. (...)

KVINNEN SOM ALDRI DØR
SIDE3.NO 2.1.2012
Henrietta Lacks døde 31 år gammel for 60 år siden. Men cellene hennes lever fremdeles, også i Norge.

Syv måneder etter at hun oppsøkte Johns Hopkins-hospitalet fordi hun kjente en klump inne i seg, døde den fargede amerikanske kvinnen Henrietta Lacks av en spesielt hissig type livmorhalskreft i 1951.

Henrietta ble begravet på en familiegravlund i Lackstown i Virginia. Familien vet ikke riktig hvor kvinnen, som er blitt en av medisinens største gaver til menneskeheten, ligger. Uansett er kvinnen uten gravstein i ettertid blitt offer for et av de største ran i medisinsk historie.

Til sin forbauselse oppdaget forskere at kreftcellene hennes ikke bare kunne holdes i live utover noen få dager: De fortsatte å vokse. Legen George Gey isolerte én celle, fikk den til å dele seg flere ganger og dyrket fram en cellelinje som han kalte He-La, etter initialene i Henriettas navn. Han gjorde det uten å innhente verken hennes eller familiens samtykke.

Finnes også i Norge
Hela ble de første laboratoriedyrkede «udødelige» menneskecellene, udødelige så lenge fundamentale betingelser for behandling er oppfylt.

En Hela-celle har en aktiv versjon av fenomenet telomerase under celledeling. Det hindrer den fortløpende prosessen som gir aldring og til slutt celledød.

Slik unngår en Hela begrensningen av antallet delinger som normale celler undergår før de dør, og Hela-celler lever videre i laboratorier over hele kloden. Og de lever og deler seg der kraftfullt og i høyt tempo. (...)

(Anm: Telomerase (no.wikipedia.org).)

ER Tubules Mark Sites of Mitochondrial Division
Science 2011; 334(6054): 358-362 (21 October)
Abstract Mitochondrial structure and distribution are regulated by division and fusion events. Mitochondrial division is regulated by Dnm1/Drp1, a dynamin-related protein that forms helices around mitochondria to mediate fission. Little is known about what determines sites of mitochondrial fission within the mitochondrial network. The endoplasmic reticulum (ER) and mitochondria exhibit tightly coupled dynamics and have extensive contacts. We tested whether ER plays a role in mitochondrial division. We found that mitochondrial division occurred at positions where ER tubules contacted mitochondria and mediated constriction before Drp1 recruitment. Thus, ER tubules may play an active role in defining the position of mitochondrial division sites. (...)

Mitochondrial Mutation Linked to Essential Hypertension
medpagetoday.com 31.3.2011
A single-letter change in DNA passed on only by women appears to be responsible for essential hypertension in a Chinese family, researchers reported.

The change affects DNA in the mitochondria, the organelles that provide a cell's energy, according to Min-Xin Guan, PhD, of Zhejiang University in Hangzhou, China, and colleagues.

The finding may help clarify the pathophysiology of maternally transmitted essential hypertension, Guan and colleagues reported online in Circulation Research. (...)

Mitochondrial Function Linked to Autism (Mitokondriell funksjon linket til autisme)
Psychiatr News 2011;46(6):1 (March 18) (American Psychiatric Association)
Treatment with antioxidants such as carnitine, coenzyme Q10, and B vitamins has been found to help some children who have both autism and mitochondrial disease.
Might mitochondria—the little packets inside cells that make energy for both brain and body—play a role in autism?

Perhaps in some cases of the disorder, two researchers believe. They are Daniel Rossignol, M.D., a primary care physician affiliated with the International Child Development Resource Center in Melbourne, Fla., and Richard Frye, M.D., Ph.D., of the University of Texas Health Science Center at Houston.

Mitochondria are best known for producing energy for the cell from oxygen and food. Because of mitochondria's role in energy production, children with mitochondrial disease have some level of dysfunction in high-energy organs such as the brain. Children with mitochondrial disease can have either normal intelligence, mental retardation, or developmental delay.

On the basis of a review of 65 studies, Rossignol and Frye concluded in a report in the January 25 Molecular Psychiatry that 1 in 20 children with autism has mitochondrial disease, which is much higher than the incidence in the general population, which is about 1 in 10,000 children. (...)

Tror at mitokondrieskader kan føre til Alzheimer
dagensmedicin.se 17.2.2011
Nye funn antyder at skade av mitokondrielt arvemateriale kan gi nevrodegenerativ sykdom.

Doktorgradsstipendiat Knut Husø Lauritzen har funnet interessante assosiasjoner mellom mitokondrielt DNA (mtDNA) og hjernefunksjon hos mus.

Skadelig protein
Ved å gi dyrene en diett med et protein som skader mtDNA, kunne Husø Lauritzen studere effektene av dette.

Han fant at nevroner i hippocampus, senteret i hjernen som er assosiert med læring og hukommelse og som er sterkt preget i sykdommmer som Alzheimers, i stor grad påvirkes av skader på mtDNA.

Nervecellene dør
Mitokondrier er viktig for nervevev som har et høyt energibehov. Husø Lauritzen fant at skadene på arvematerialet i disse energiproduserende organellene ga nedbrytning og død av nerveceller.

Nettopp dette karakteriserer nevrodegenerative sykdommer.

Nedsatt læringsevne
Hos musene ble det observert en uvanlig adferd med nedsatt læringsevne. Det ble også blant annet oppdaget kollaps av mitokondriell dynamikk og distribusjon, med opphoping av mitokondrier i den nervecellekroppen og påfølgende reduksjon i synapseområder der energi er viktig for overføring av nervesignaler.

Husø Lauritzen disputerer for sin doktorgrad ved Universitetet i Oslo 21. februar. (...)

Gånghastighet avslöjar hur gammal du blir
sverigesradio.se 4.1.2011
En stor studie visar att hur fort äldre personer går ger en bra indikation på hur gamla de kan bli. 35000 personer deltog i studien över ett stort antal år.

esultaten visar att både män och kvinnor som har en vanlig gånghastighet på över en meter per sekund (4 km/h) kan vänta sig att leva längre än genomsnittet.

Män i Sverige kan i genomsnitt räkna med att leva till en ålder av cirka 79 år, kvinnor 83 år. Men ofta är det viktigt för läkare att få en mer exakt uppskattning av en patients förväntade livslängd, för att kunna ge rätt vård. I det sammanhanget är det här viktigt.

Det går förstås inte att hoppas på att leva längre bara genom att gå fortare. Snarare tror forskarna att långsam gång kan vara ett tecken på små skador i nervsystem, muskler, hjärta eller andning.

(Anm: Role of Gait Speed in the Assessment of Older Patients. JAMA. 2011;305(1):93-94.)

(Anm: Gait Speed and Survival in Older Adults. JAMA. 2011;305[1]:50-58.)

Mitochondrial Dysfunction in Autism (Mitokondriell dysfunksjon ved autisme)
JAMA. 2010;304(21):2389-2396 (December 1)
JAMA. 2010;304(21):2389-2396. doi:10.1001/jama.2010.1706
Context Impaired mitochondrial function may influence processes highly dependent on energy, such as neurodevelopment, and contribute to autism. No studies have evaluated mitochondrial dysfunction and mitochondrial DNA (mtDNA) abnormalities in a well-defined population of children with autism.

Objective To evaluate mitochondrial defects in children with autism. (...)

Conclusion In this exploratory study, children with autism were more likely to have mitochondrial dysfunction, mtDNA overreplication, and mtDNA deletions than typically developing children. (...)

Mitochondrial dynamics: quantifying mitochondrial fusion in vitro
BMC Biology 2010, 8:99 (26 July)
Mitochondria are mainly known as the 'power house' of eukaryotic cells because they are able to catalyze the production of ATP through oxidative phosphorylation. However, these organelles are not restricted to this unique function but fulfill a number of other tasks, including regulation of calcium homeostasis and amino acid metabolism or the citric acid and the urea cycles, and as such participate actively in life and death of cells. Mitochondria contain their own genome that is packaged into nucleoid-like structures containing several mitochondrial DNA (mtDNA) molecules. In humans, each mtDNA molecule encodes 13 proteins, 2 ribosomal RNAs and 22 tRNAs. To function correctly, mitochondria need to be dynamic: they move, fragment and fuse continuously. On one hand, fragmentation or fission is necessary to produce new mitochondria from a 'mother mitochondrion' or to isolate and target damaged parts of one mitochondrion for degradation by mitophagy [1]. (...)

Mitochondrial Mutations
JAMA. 2010;303(17):1686 (May 5)
Mutations in the MFN2 gene are the most common cause of the neurodegenerative disease Charcot-Marie-Tooth type 2A (CMT2A), but it has been unclear how these defects lead to the selective degeneration of the long peripheral axons that is characteristic of the disorder. Now, a new study shows how defects in the protein encoded by MFN2, mitofusin 2 (Mfn2), can disrupt the movement of mitochondria along nerve cells (Misko A et al. J Neuroscience. 2010;30[12]:4232-4240). (...)

(Anm: Charcot-Marie-Tooths sykdom (nhi.no).)

Nobelpris for mitotisk klokke
Leder
Tidsskr Nor Legeforen 2009; 129:2470 (3.12.2009)
Historien bak årets nobelpris er gammel, men langt fra ferdigskrevet. Oppdagelsen av telomerprinsippet har endret vår forståelse av mitosekontroll, stamceller og kreftutvikling og kan åpne for nye terapeutiske strategier

Nobelprisen i fysiologi eller medisin for 2009 er tildelt Elizabeth H. Blackburn, Carol W. Greider og Jack W. Szostak for «oppdagelsen av hvordan kromosomene er beskyttet av telomerer og enzymet telomerase». Allerede i 1930-årene la cytogentikere merke til at kromosomer tenderte til å hefte seg sammen og nedbrytes hvis endestykkene manglet. Hermann Muller (nobelpris 1946) og Barbara McClintock (nobelpris 1983) konkluderte derfor at kromosomendene spiller en avgjørende rolle for kromosomets stabilitet (1). (...)

Når basale nyvinninger skal overføres til medisinsk nytte, er som kjent fallhøyden proporsjonal med det antatte potensialet. Mye taler likevel for at årets nobelpris ikke blir den siste som tilfaller telomerrelatert forskning. (...)

Motion gör oss smartare
dn.se 30.11.2009
Motion är det som gäller om Sverige ska få en smartare befolkning. Killar som har bra kondition i 18-årsåldern presterar bättre på intelligenstester än sina mer stillasittande kamrater. Att dra ned på skolidrotten är feltänkt, enligt forskare.

Motion påverkar kroppen på en mängd olika sätt. Studier har pekat på bland annat förbättrad sömn, bättre immunförsvar, lägre risk för sjukdomar som depression och demens, starkare skelett och bättre förmåga att reglera blodtryck och blodsocker.

Dessutom frisätter fysiska aktivitet olika tillväxtfaktorer i hjärnan som leder till fler blodkärl. Cellernas kraftverk, mitokondrierna, blir fler i de delar av hjärnan som exempelvis styr rumslig uppfattning och logiskt tänkande. (...)

- Det stämmer logiskt med vad man ser för effekter i hjärnan efter att ha joggat i en halvtimme. Då har man ett ökat blodflöde framför allt i hjärnans främre delar som har hand om den typen av tankeverksamhet, säger Maria Åberg.

De med bäst kondition i 18-årsåldern gick också vidare till högre studier oftare än de med sämre kondition, enligt resultaten som publiceras i vetenskapstidskriften Pnas. (...)

Exercise May Slow Telomere Shortening, Aging (Trening kan forsinke forkortingen av telomerer, eldring)
medpagetoday.com 30.11.2009
Endurance training appears to have anti-aging effects at the molecular level, researchers found.

Middle-aged marathoners and triathletes who had been training for decades had significantly less telomere erosion than their more sedentary counterparts, according to Ulrich Laufs, MD, of Saarland University in Hamburg, Germany, and colleagues.

Both younger track-and-field athletes and the older runners had upregulation of telomere-stabilizing proteins and decreased expression of vascular apoptosis regulators in circulating leukocytes compared with individuals who did not exercise frequently, the researchers reported online in Circulation: Journal of the American Heart Association.

"This is direct evidence of an anti-aging effect of physical exercise," Laufs said in a statement.

"Our data improve the molecular understanding of the vasculoprotective effects of exercise and underline the potency of physical training in reducing the impact of age-related diseases," he and colleagues wrote. (...)

(Anm: Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall. Circulation 2009. Published online before print November 30.)

Mitochondrial gene therapy shows promise for neurodegenerative diseases
ptproductsonline.com 18.10.2009
NEW YORK (Reuters Health) - New technology that corrects genetically defective mitochondria could potentially be used to treat mitochondrial diseases characterized by deficiencies of energy production.

In a presentation this week at the 134th annual meeting of the American Neurological Association in Baltimore, Dr. Shilpa Iyer, from the University of Virginia, Charlottesville, explained that hereditary as well as sporadic neurodegenerative diseases can arise from point mutations or deletions in mitochondrial DNA that contribute to bioenergetic failure. (...)

In cytoplasmic hybrids bearing mitochondria with mutations linked to Leber's hereditary optic neuropathy or Parkinson's disease, it took 2 weeks for gene therapy to increase mitochondrial DNA copy number, gene expression, and respiration. Ten weeks after the single treatment, new mitochondria were abundant and respiration was normalized.

Dr. Iyer also reported that normal mice treated with weekly IV injections of rhTFAM showed increases in multiple electron transport chain proteins, mitochondrial respiration in skeletal muscle and in the brain, and increases in motor endurance, along with reduced damage from oxidative stress. (...)

Mitochondrial gene replacement in primate offspring and embryonic stem cells
Nature 2009;461:367-372 (17 September)
Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. (...)

Herb May Offer Hope for Autoimmune Diseases (Urt kan gi håp for autoimmune sykdommer)
healthfinder.gov 4.6.2009
In lab and mice studies, compound halts disease without crimping immune system.

THURSDAY, June 4 (HealthDay News) -- A compound derived from hydrangea root, an herb used in traditional Chinese medicine, halted the progression of an autoimmune disorder in laboratory mice and human cells, new research shows.
What makes the compound, halofuginone, so promising, the researchers said, is that it slowed progression of the disease without suppressing normal immune system functioning.

A major drawback to current treatments for autoimmune disease is increased risk for infections because of suppressed immune system functioning, according to the study, which appears in the June 5 issue of Science.

"This is really the first description of a small molecule that interferes with autoimmune pathology but is not a general immune suppressant," said the study's lead study author, Mark Sundrud, from the cellular and molecular medicine program and the Immune Disease Institute at Children's Hospital Boston. (...)

(Anm: Halofuginone Inhibits T_H17 Cell Differentiation by Activating the Amino Acid Starvation Response. Science 2009;324(5932):1334-1338 (5 June).)

Patienter indbudt til te-konklusioner
farma.ku.dk 22.5.2009 (Københavns Universitet - Det Farmaceutiske Fakultet)
En helt særlig te benyttes som lægemiddel til behandling af type 2-diabetes i den nigerianske folkemedicin – forskere på Institut for Medicinalkemi har netop afsluttet et fire måneder langt klinisk forsøg på 23 patienter med type-2-diabetes, og postdoc Joan Campbell-Tofte og lektor Per Mølgaard er mere end tilfredse med resultatet. (...)

– Hos den patientgruppe, der drak teen, blev antallet af polyumættede fedtsyrer øget. Det er godt for kroppens celler, fordi det polyumættede fedt gør cellemembranerne mere gennemtrængelige, hvilket resulterer i, at cellerne bliver bedre til at optage glukose fra blodet, forklarer Joan Campbell-Tofte.
Forskerne håber, at nye kliniske forsøg og videnskabelige undersøgelser på sigt vil resultere i et nyt behandlingstilbud til type 2-diabetikere. (...)

Ämne i gurkmeja skyddar cellväggar
sr.se 14.4.2009
Kryddväxten gurkmeja, som används mycket i indisk mat, har också länge använts som medicinalväxt. Nu har forskare vid University of Michigan visat att ett ämne i gurkmeja har en direkt effekt på våra celler som gör de mer motståndskraftiga. (...)

Enligt Pernilla Wittung-Stafshede har det hittills varit mycket svårt att studera proteiner som just sitter i cellmembran, men forskarna vid University of Michigan har använt nya avancerade biofysikaliska metoder som kan vara vägledande för annan biomedicinsk forskning. (...)

(Anm: Determining the Effects of Lipophilic Drugs on Membrane Structure by Solid-State NMR Spectroscopy: The Case of the Antioxidant Curcumin” J. Am. Chem. Soc. 2009;131(12):4490-4498.)

Researchers Uncover Why Turmeric Helps Heal (Forskere avdekker hvorfor gurkemeie hjelper til med leging)
healthfinder.gov 5.6.2009
Component of ancient spice makes cells more resistant to infection, report says.

FRIDAY, June 5 (HealthDay News) -- Modern technology has revealed the ancient secret behind the healing power of turmeric, a spice regarded as "holy powder" in India.

Turmeric has been used for centuries to treat wounds, infections and other ailments. It's long been believed that curcumin -- the main ingredient in turmeric -- is responsible for its healing power, but it hasn't been known how curcumin works inside the body, explained researcher Ayyalusamy Ramamoorthy and colleagues.

They used solid-state NMR spectroscopy to examine molecules of curcumin and found that they act like a "biochemical disciplinarian." The molecules insert themselves into cell membranes and make the membranes more stable and orderly in a way that boosts cells' resistance to infection by disease-causing microbes.

The study was recently published in the Journal of the American Chemical Society. (...)

Gurkemeie kan forebygge kreft
aftenposten.no 20.12.2010
Gurkemeie er for mange kjent som en rimeligere versjon av safran, på grunn av den gule, fine fargen. Men krydderet kan muligens kurere betennelser – og forebygge kreft.

Gurkemeie inneholder stoffet curcumin, som interesserer forskere fordi det ser ut til å virke på «alt». Vel å merke på celler i laboratoriet.

Tilføres derimot curcumin i store doser til en hel menneskekropp, med nervesystem, immunsystem, fordøyelsessystem og det hele, klarer man knapt å registrere det i kroppen, ifølge forskning.no. (...)

Gurkemeie – fra krydder til medisin
forskning.no 19.12.2010
Gurkemeie inneholder stoffet curcumin, som tiltrekker forskere fra hele verden, fordi det ser ut til å virke på ”alt”. Vel å merke på celler i laboratoriet.

Tilføres derimot curcumin i store doser til en hel menneskekropp, med nervesystem, immunsystem, fordøyelsessystem og det hele, klarer man knapt å registrere det i kroppen.

– Før curcumin eventuelt kan bli til medisin må dette problemet løses, sier forsker Purusotam Basnet, ved institutt for farmasi ved Universitetet i Tromsø.

Som krydder i det daglige kostholdet hevder en del forskere og kreftleger at gurkemeie kan dempe eller kurere betennelsestilstander i kroppen, samt forebygge kreft og andre kroniske sykdommer. (...)

Mitochondria Malfunction May Underlie Some Severe Psychiatric Disorders
Psychiatr News 2009;44(7):17 (April 3) (American Psychiatric Association)
Move over, neurotransmitters: studies of mitochondria, the tiny engines that power cells, may hold clues to a new perspective on the development of mental illness.

First there were evil spirits, then Freud and psychological theories, then neurotransmitters.

Next up for consideration as a possible source of psychiatric disorder may be mitochondria, the tiny subcellular bodies that provide energy to the body's cells. (...)

Mitokondrienes rolle ved Alzheimers sykdom
Tidsskr Nor Legeforen 2009; 129:400 (26.2.2009)
Mitokondrienes selvdestruksjonsmekanisme medvirker trolig til utvikling av Alzheimers sykdom.

Man vet at avleiring av β-amyloide plakk i hjernen er viktig i patogenesen ved Alzheimers sykdom. Man vet også at mitokondriene skades av løselig β-amyloid. En amerikansk forskergruppe har nå vist ved cellestudier at løselig β-amyloid i mitokondriene interagerer med proteinet cyklofilin D (CypD), og dette øker mitokondrielt stress. Funnene indikerte i tillegg at interaksjonen mellom løselig β-amyloid og CypD åpner poren mPTP i den indre mitokondriemembranen, noe som medfører en influks av kalsiumioner med påfølgende mitokondrieskade (1). (...)

Function of Mitochondrial Stat3 in Cellular Respiration
Science 2009;323(5915):793-7978 (6 February)
Cytokines such as interleukin-6 induce tyrosine and serine phosphorylation of Stat3 that results in activation of Stat3-responsive genes. We provide evidence that Stat3 is present in the mitochondria of cultured cells and primary tissues, including the liver and heart. In Stat3–/– cells, the activities of complexes I and II of the electron transport chain (ETC) were significantly decreased. We identified Stat3 mutants that selectively restored the protein's function as a transcription factor or its functions within the ETC. In mice that do not express Stat3 in the heart, there were also selective defects in the activities of complexes I and II of the ETC. These data indicate that Stat3 is required for optimal function of the ETC, which may allow it to orchestrate responses to cellular homeostasis. (...)

Antidepressant enhances chemotherapy drug
upi.com 24.12.2008
TEL AVIV, Israel, Dec. 24 (UPI) -- Researchers in Israel say a popular antidepressant enhances the effect of an anticancer drug used with colon cancer.

The Tel Aviv University study validates that the antidepressant with the chemical name fluoxetine and the trade name of Prozac regularly prescribed to ease the emotional pain of those with cancer also helps enhance the effect of the colon cancer drug doxorubicin by more than 1,000 percent.

Prozac worked to block the cancer drug from leaving the interior of the cancer cell and poisoning the healthy non-cancerous cells that surrounded it. (...)

Joggere forbrenner ekstra kalorier i søvne
vg.no 25.10.2008
(VG Nett) Ny forskning viser at de som driver med kondisjonstrening fortsetter å forbrenne kalorier hyppigere enn andre - også når de hviler.

Ifølge New Scientist har forskere fra Yale university gjennom forsøk funnet ut at menn som løper mer enn fire timer i uka forbrenner 54 prosent mer enn andre også når de ikke trener. (...)

Kondisjonstreningen øker nemlig produksjonen av det i cellene (mitokondrium) som omgjør sukker og fett til en viss type molekyler, og som fungerer som cellenes motor.

Det underbygger også at treningen beskytter mot livsstilssykdommer som diabetes 2. (...)

(Anm: Runners burn more calories – even at rest (newscientist.com 25.10.2008).

Increased substrate oxidation and mitochondrial uncoupling in skeletal muscle of endurance-trained individuals. Proceedings of the National Academy of Sciences Published online before print October 20, 2008.)

Manipulating the Metazoan Mitochondrial Genome with Targeted Restriction Enzymes
Science 2008;321(5888):575 - 577 (25 July)
High copy number and random segregation confound genetic analysis of the mitochondrial genome. We developed an efficient selection for heritable mitochondrial genome (mtDNA) mutations in Drosophila, thereby enhancing a metazoan model for study of mitochondrial genetics and mutations causing human mitochondrial disease. Targeting a restriction enzyme to mitochondria in the germline compromised fertility, but escaper progeny carried homoplasmic mtDNA mutations lacking the cleavage site. Among mutations eliminating a site in the cytochrome c oxidase gene, mt:^1CoIA302T was healthy, mt:^1CoIR301L was male sterile but otherwise healthy, and mt:^1CoIR301S exhibited a wide range of defects, including growth retardation, neurodegeneration, muscular atrophy, male sterility, and reduced life span. Thus, germline expression of mitochondrial restriction enzymes creates a powerful selection and has allowed direct isolation of mitochondrial mutants in a metazoan. (...)

- Menneskeheten var nær ved å bli utryddet
vg.no 26.4.2008
(VG Nett) For 70 000 år siden var menneskeheten redusert til rundt 2000 individer, hevder forskere. (...)

- Omfattende klimaforandringer førte til at menneskene ble skyvet fra hverandre. Men så kom de tilbake fra randen av tilintetgjørelse og befolket verden på ny. (...)

Den nye studien ser på mitokondrisk DNA fra Khoi - og San-folket i Sør-Afrika, som igjen skal stamme fra mennesker som levde for 90 000 til 150 000 år siden. (...)

Fetal Cocaine Exposure has Lasting Effects
ivanhoe.com 14.4.2008
(Ivanhoe Newswire) -- Cocaine abuse by young women of childbearing age is a growing problem. Now, a new study done on monkeys indicates babies exposed to cocaine in the womb may have long lasting brain changes -- especially males.

The research showed adult male monkeys who were exposed to cocaine in the womb appear to have altered function in dopamine receptors in their brains. Dopamine is similar to adrenaline. It affects brain processes that control movement, emotional response and ability to experience pleasure and pain. There are five known dopamine receptors. In humans, changes in them are associated with vulnerability to drug abuse.

Though the monkeys in the study experienced fetal cocaine exposure, they had no contact with the drug after birth. When the research team studied them at age 13, they found the male monkeys exposed to the drug in the womb yawned twice as much in a 30-minute period as the males who were not exposed. (...)

Link Between Autism & Muscle Weakness?
ivanhoe.com 14.4.2008
(Ivanhoe Newswire) -- Some children with autism may also have a genetic defect that causes muscle weakness.

Research identified a subset of autistic children who also had a genetic defect, which causes mitochondrial disease. (...)

FDA looks at link between medications, depression (FDA ser på link mellom legemidler, depresjon)
latimes.com 14.4.2008
Federal regulators warn that an array of drugs could play a role in spurring thoughts of suicide or other psychiatric symptoms.

As symptoms of depression go, there is none much clearer than having thoughts of suicide.

But a spate of recent announcements from federal health officials suggests a surprising new interpretation of suicidal fantasies and the depression they are thought to signal: Sometimes, sadness, anxiety and self-destructive thoughts are not symptoms but side effects -- of medicine.

In this year alone, federal regulators have warned that a surprising array of drugs could play a role in spurring thoughts of self-destruction. Medicines that treat epilepsy, asthma and influenza are now under suspicion, as is one that helps smokers kick the tobacco habit. (...)

Freedom of Expression
Science 2008;319(5871):1781 (28 March)
As in civil society, where there must necessarily be checks and balances on freedom of expression, cells have evolved a range of mechanisms to regulate the expression of their constituent genes. By far the best-understood medium for gene regulation is the protein transcription factor. The broad set of rules by which these regulators operate is outlined by Hobert (p. 1785). However, new and unexpected gene regulatory systems have been discovered in the past decade, perhaps the most important of which involve microRNAs (miRNAs). Hobert compares the action of these small noncoding RNAs, found in many eukaryotes, with their proteinaceous counterparts, showing that miRNAs share many similar activities but also display unique traits in their compartmentalization, rapid reversibility, and evolvability. Makeyev and Maniatis (p. 1789) provide examples of the profound systemwide influence that miRNAs can have on gene expression programs. (...)

Prevalence of mitochondrial DNA disease in adults
Annals of Neurology 2008;63(1):35–39 (January)
Objective Diverse and variable clinical features, a loose genotype–phenotype relationship, and presentation to different medical specialties have all hindered attempts to gauge the epidemiological impact of mitochondrial DNA (mtDNA) disease. Nevertheless, a clear understanding of its prevalence remains an important goal, particularly about planning appropriate clinical services. Consequently, the aim of this study was to accurately define the prevalence of mtDNA disease (primary mutation occurs in mtDNA) in the working-age population of the North East of England. (...)

Results In this population, we found that 9.2 in 100,000 people have clinically manifest mtDNA disease, making this one of the commonest inherited neuromuscular disorders. In addition, a further 16.5 in 100,000 children and adults younger than retirement age are at risk for development of mtDNA disease.

Interpretation Through detailed pedigree analysis and active family tracing, we have been able to provide revised minimum prevalence figures for mtDNA disease. These estimates confirm that mtDNA disease is a common cause of chronic morbidity and is more prevalent than has been previously appreciated. Ann Neurol 2007. (...)

Stort nytt genkart på vei
forbruker.no 28.1.2008
Ny forskning om menneskekroppens arvemateriale vil kunne gi viktig kunnskap om sykdommer og spesialisere legemidler til enkeltindividet. (...)

Prislappen på prosjektet er forventet å bli mellom 30 og 50 millioner dollar.
kilde: 1000genomes.org (...)

Jakten på livets gåte
aftenposten.no 23.9.2007
Du har hans nese. Han har din munn. Men hvorfor? Spørsmålet har fascinert oss gjennom hele historien. Jakten på svaret har resultert i alt fra folkemord til nobelpriser og ny filosofi. (...)

Dette bør du vite om genene
Genene våre er lagret i kromosomer i cellekjernen.
All genetisk informasjon i alle organismer er basert på samme firebokstavers DNA-alfabet. Genetisk informasjon fra én organisme kan derfor leses av en annen. (...)

Kunstige cellemembraner ga innsikt i bivirkninger
uib.no 7.9.2007
(...) Forskning ved UiB viser at visse legemidler som brukes mot blant annet psykoser, kan virke gjennom en annen mekanisme enn man hittil har trodd. Dersom det stemmer, kan det gi ny innsikt i hvorfor effektive legemidler kan gi plagsomme bivirkninger (...)

Svakheter i studien
Song er raskt ute med å påpeke to faktorer som er åpenbare svakheter i studien. For det første, har han gjort forsøk på kunstige membraner, som bare består av bare de to fosfolipidlagene – og ikke proteiner, kolesterol eller andre typiske bestanddeler. Dermed kan man ikke si noe om de faktisk interaksjonene som foregår når alle bestanddelene er på plass. (...)

Mitochondrial DNA Haplogroups and Age-Related Maculopathy
Arch Ophthalmol. 2007;125:1235-1240.
(...) Conclusions Our findings of associations between different haplogroup types and prevalent ARM or ARM lesions suggest that these haplogroups may be genetic markers indicative of an individual's susceptibility to ARM. (...)

Genenes framtid
Dag O. Hessen
dagbladet.no 12.8.2007
Arv, gener og identitet er tett sammenkoblet – kanskje for tett? Oppnøsting av arvelighetens gåte har vært en av menneskehetens største intellektuelle triumfer, og det er en dramatisk historie om faglige seierherrer og tapere, og ideologisert og politisert vitenskap. (...)

Den klassiske genetikk viste oss prinsippene for arv. Genteknologien representerer anvendelsen av disse fundamentale innsiktene. Vi har nå fått muligheten til å endre livets spilleregler. Vi står bare ved begynnelsen av genteknologiens tidsalder og det eneste man kan si med sikkerhet er at enhver spådom om hvor dette vil føre oss trolig tar feil.

Dag O. Hessen har sammen med Thore Lie skrevet boka ”Genenes gåte” som utgis i dag.

«Vi har nå fått muligheten til å endre livets spilleregler.» (...)

New Clues to Neurological Diseases Discovered
healthfinder.gov 5.7.2006
Findings could lead to new treatments, two studies suggest

-- Researchers have found that genetic abnormalities in molecules that regulate neuron growth may be at the root of Down syndrome and Alzheimer's disease.
These molecules, known as neurotrophins, are taken up by neurons in sac-like carriers called endosomes and transported to the main cell body, where they take charge of neuronal development and connectivity by activating protein switches called Trk receptors.

Now, two separate reports in the July 6 issue of Neuron show that a malfunction of a single gene disrupts the transport of neurotrophins and that restoring normal levels of a Trk receptor could reverse the death of neurons. (...)

Setback for a Novel Heart-Attack Treatment
nytimes.com 1.3.2006
A radical new treatment for heart attack patients turns out to be wholly ineffective when tested under rigorous conditions, researchers in Germany say in a report that severely undercuts an apparently promising form of stem cell therapy.

Their finding renews a longstanding debate among medical researchers as to whether the basic biology of stem cells needs to be far better understood before testing cell-based therapies in patients is worthwhile.

The new treatment entailed injecting heart attack patients with a hormone that induces the bone marrow to send blood-making cells out into the bloodstream. Experiments with animals had suggested that the blood-making cells would home in on the damaged heart tissue, transform into heart muscle cells and in effect rebuild the heart.

That possibility excited clinicians because the heart has very little capacity to regenerate itself after a heart attack. Instead, it replaces the dead cells with scar tissue that impedes its function.