Découverte de deux gènes qui aident à combattre la sclérose en plaque

ouest-france
01:04 - samedi 12 septembre 2009

Des chercheurs américains ont découvert deux gènes impliqués dans la restauration du système nerveux central de souris atteintes de sclérose en plaque. Cette découverte offre un nouvel espoir pour mettre au point des thérapies plus efficaces et prédire la façon dont les patients répondront à cette maladie auto-immune dégénérative.

L'équipe d'Allan Bieber, spécialiste des neurosciences à la clinique Mayo dans le Minnesota, a étudié des souris atteintes d'une forme chronique de maladie évolutive assimilée à la sclérose en plaque et a cartographié les gènes de celles qui ont spontanément réparé les dommages causés par la maladie. Les chercheurs ont découvert deux facteurs génétiques déterminants dans cette évolution positive

How PCBs May Hurt the Brain

New Studies Shed Light on Exposure to Environmental Toxin and Development of Brain Cells

Kathleen Doheny
WebMD Health News
April 13, 2009

Exposure to environmental toxins known as PCBs have long been linked with behavioral and developmental problems in children, but scientists could never say exactly how PCBs (polychlorinated biphenyls) might adversely affect the brain and lead to the problems.

Now, scientists think they may know.

The chemicals adversely affect the development of brain cells and also make brain circuits "overexcited," which has been linked in previous research to developmental problems, according to researcher Isaac N. Pessah, PhD, a professor of molecular biosciences and director of the University of California Davis Center for Children's Environmental Health.

"We think we have identified the way in which a broad class of environmental contaminants influences the developing nervous system and may contribute to neuro-developmental impairments such as hyperactivity, seizure disorders, and autism," says Pessah, a co-author on a trio of new studies examining the issue. The latest of the three is published online today in PLoS-Biology.

The findings of the three studies are called a "turning point" by another expert in the field.

One surprise finding: low levels of PCB exposure sometimes have greater ill effects than high-dose exposures.

PCBs were widely used for years in many products such as electronic components, pesticides, caulking, and flame retardants, but their production was banned in the U.S. in 1979.

Even so, the chemicals persist in the environment because they don't break down easily, explaining why high levels of PCBs can still be detected in people and in animals. PCBs are found in air, water, soil, and contaminated foods such as fish.

PCB Exposure and Effect on Learning and Brain Cells

In one of the three new studies, exposures to low doses of PCBs in animals hampered their ability to learn to swim a maze, a common test of animal learning.

The low PCB doses also adversely affected the plasticity of the animals' dendrites -- small projections branching out from the neurons or nerve cells that get signals from other cells in the body.

"This plasticity is very important for learning and memory," says study researcher Pamela Lein, PhD, associate professor of neurotoxicology at the UC Davis School of Veterinary Medicine.

The study was published in March in Environmental and Health Perspectives.

Problems in dendrite plasticity and growth have already been implicated in disorders such as autism, schizophrenia, and mental retardation, Lein says.

Lein and colleagues compared the effects of low-dose PCB exposure, high-dose exposure, and no exposure in three groups of rats that had been trained to swim and find an escape platform in a maze, and three groups not trained to swim the maze.

"The PCB treatments did affect the learning and memory," she says. "The effects were seen in the low-dose group but not the high-dose." Those in the low-dose trained group took longer to learn to swim and escape the maze, she says.

In the high-dose group, she says, the exposure may have triggered a compensatory mechanism that protected the brain cells from harm.

PCB Exposure: The Tissue Study

In a second study, the researchers looked at tissue from the animals' hippocampus, an area of the brain that regulates memory and emotion, and measured the "excitability" of neurons there before and during exposures to two different PCBs.

With one of them, says Pessah, "we can get an enhancement of excitability." Normally, information processing in the brain depends on a balance between excitation and inhibition of the neurons.

"Too much excitability is bad for the brain," Pessah says. Many neuro-developmental disorders, he says, including autism and attention deficit hyperactivity disorder or ADHD, "are thought to involve an imbalance between inhibition and excitability."

What they found in this study, he says, is that "even low levels [of PCBs] can tip the balance in the brain." The report is published in March in Toxicology and Applied Pharmacology.

PCB Exposure: The Cellular Level Clues

Finally, the researchers went to the cellular level, trying to find out more specifically how the PCBs change brain cell development as they found in the animal study and how they change the neurons' excitability, as seen in the study on brain tissue.

In the lab, they exposed receptors within the cells that regulate the release of calcium, crucial to maintain normal signaling from cell to cell, to PCBs. When they used electron microscope to create high-resolution images of the interaction between the receptors and the PCBs, they found the chemical binds to the receptors and adversely affects the calcium release. This interference accounts for the findings in the other two studies, Pessah says.

PCB Studies: Second Opinion

"I think that these studies represent a kind of a turning point for our recognition of how these chemicals, PCBs, can interfere with brain development," says R. Thomas Zoeller, PhD, professor of biology at the University of Massachusetts, Amherst. He was a journal reviewer for one study and reviewed the other two for WebMD.

"They are looking at a limited number of forms of PCB chemicals and they are linking exposures to very specific changes in proteins in the nervous system that impact brain development and behavior," he says. Because the animal model studied developmental events that are akin to human developmental events, ''for the first time we are getting a clear view of how these chemicals can impact the brain in humans," he says.

PCB Studies: Practical Applications

The new findings will add weight to the studies finding a link between exposures to PCBs and developmental problems, Lien says. "For the first time, we now have a plausible biological mechanism to explain the effect of PCBs on behavior."

One practical application of the research? Scientists may use the findings to evaluate the safety of numerous chemicals produced to take the place of PCBs, Zoeller says. "Science can't keep up with the rapid kinds of chemical changes that industry can manufacture," he says. "It would be great if we could get out in front of it and identify dangerous chemicals before people are being exposed."

The research findings may also make experts who thought lower-dose PCB exposures were not a problem think again, Pessah says.

'Take control of your sleep, before it takes control of you'

Sify news
Monday, 23 March , 2009, 11:06

New Delhi: If you didn't sleep well last night or feel exhausted all day long, you are probably one of thousands suffering from sleeping disorders. It's possible that hypertension, acidity and several other lifestyle diseases are playing havoc with your sleep.

Good sleep helps you to be alert, awake and keeps you energetic throughout the day and hence a good night's sleep is vital for good health, experts say.

"As sleep is vital to our health and well-being, we must not cut ourselves short from the amount of sleep that we get or suffer from sleep problems. Take control of your sleep problems before it takes control of you," advised Ramnathan Iyer, a doctor who treats patients with sleep disorders.

A good night's sleep boosts immunity

Insomnia refers to the difficulty in initiation, maintenance, duration or quality of sleep. People may experience poor concentration, lower productivity and poorer work quality as a result of insomnia.

Sleep disorders can also make a person fatigued, irritable or forgetful and can lead to strained relationships.

Mumbai-based psychiatrist Manoj Bhatawadekar said: "To prevent or relieve sleep problems and safeguard sleep, making it more restful and pleasurable, it helps to practise good sleep hygiene."

Study links normal sleep and healthy ageing

A good 'sleep hygiene' would entail regular sleep or wake schedule, avoiding naps especially in the evenings, increase exercise, avoid intake of caffeine and alcohol just before sleeping, and schedule reasonable daytime work hours, Bhatawadekar said.

Many experts across the country from the Indian Sleep Disorders Association (ISDA) in association with Abbott India Limited, a health care company, have declared March 3 to April 7 as Sleep Awareness Month to generate awareness about the importance of sleep hygiene.

J C Suri, a doctor and president ISDA, said: "Sleep is important for mental, physical and emotional well-being."

Losing sleep? Blame it on long working hours

Iyer, who is ISDA's west regional governor, stressed: "Early assessment and action can prevent short-term sleep problems from developing into a chronic one."

Hypertension, arthritis, diabetes, acidity and some medications, including some heart medications, may even cause loss of sleep and stress.

When insomnia occurs in the context of chronic illness, it tends to be more severe than other forms of insomnia and usually involves sleep maintenance difficulties. A recent survey revealed that many lifestyle diseases also surfaced as a result of sleep disorders.

Sleep chemical eases brain disorders

Almost two-thirds of those surveyed reported the presence of at least one medical condition. These included 29 percent suffering from hypertension, 28 percent from arthritis, 19 percent coping with heartburn or gastroesophageal reflux disease, 18 percent battling depression, 11 percent dealing with diabetes, 10 percent with heart disease and 5 percent struggling with a lung disease. Obesity also was associated with a greater number of sleep-related problems.

People who reported a medical diagnosis were more likely than people without a diagnosis to sleep less than six hours per night on weekdays and experience symptoms of insomnia, the survey found.

Stem cells could save stroke victims

John von Radowitz
The Independent
Mon, 09 Mar 2009

Disabling strokes could one day be treated by replacing damaged brain tissue with stem cells, scientists have shown.

Researchers used a new technique to insert therapeutic stem cells into the brains of rats with pinpoint accuracy.

Once implanted the cells began to form new brain tissue and nerve connections.

The work is at an early stage and does not yet prove that stroke symptoms such as paralysis can be reversed.

But it demonstrates that lost brain tissue can be replaced with stem cells targeted at sites of damage.

Stem cells are immature cells with the ability to take on any of a number of specialist roles.

In previous animal experiments, stem cells implanted into the brain have tended to migrate to surrounding healthy tissue rather than fill up the hole left by a stroke.

Scientists from King's College London and the University of Nottingham overcame the problem by loading the cells onto biodegradable particles.

These were then injected through a fine needle to the precise site of damage, located using a magnetic resonance imaging (MRI) scanner.

Once implanted, the particles disappeared leaving gaps for the growth of new tissue and nourishing blood vessels.

The cells, derived from stem cells taken from mouse embryos, had already progressed some of the way to becoming neurons.

They were attached to particles made from a biodegradable plastic-like polymer called PLGA.

Dr Mike Modo, leading the King's College team from the university's Institute of Psychiatry, said: "The stem cell-loaded PLGA particles can be injected through a very fine needle and then adopt the precise shape of the cavity. In this process the cells fill the cavity and can make connections with other cells, which helps to establish the tissue.

"Over a few days we can see cells migrating along the scaffold particles and forming a primitive brain tissue that interacts with the host brain. Gradually the particles biodegrade leaving more gaps and conduits for tissue, fibres and blood vessels to move into."

Colleague Kevin Shakesheff, Professor of Advanced Drug Delivery and Tissue Engineering at the University of Nottingham, said: "This was a great collaborative project with the Kings College team and hopefully this technology will be taken to the clinical setting soon. Repairing damaged brain tissue is one of the ultimate challenges in medicine and science. It is great that we are now one step closer to achieving that goal."

The next stage will be to apply a "growth factor" chemical called VEGF with the particles to encourage the creation of new blood vessels.

The research, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), is reported in the journal Biomaterials.

Strokes occur when part of the brain dies off because of a blocked or burst blood vessel.

An estimated 150,000 strokes occur in the UK each year, 67,000 of which are fatal.

Strokes cause more disability than any other chronic condition. Around 300,000 people in the UK are moderately or severely disabled because of a stroke.

Joe Korner, from the Stroke Association charity, said: "This research is another step towards using stem cell therapy in treating and reversing the brain damage caused by stroke. It is exciting because researchers have shown they are able to overcome some of the many challenges in translating the potential of using stem cells into reality.

"The potential to reverse the disabling effects of stroke seems to have been proved. However the development of stem cell therapy for stroke survivors is still in the early stages and much more research will be needed before it can be tested in humans or used in practice.

"Every five minutes someone in the UK has a stroke and it is vital that we do all we can to help those affected by stroke."

Professor Douglas Kell, chief executive of the BBSRC, said: "Stroke is a leading cause of disability in industrialised countries. It is reassuring to know that the technology for treating stroke by repairing brain damage is getting ever closer to translation into the clinic. This crucial groundwork by Dr Modo and his colleagues will surely be a solid foundation of basic research for much better treatments in the future."

Anthony Hollander, Professor of Rheumatology and Tissue Engineering at the University of Bristol, said: "We are only just beginning to understand how to use tissue engineering to cure diseases. This study shows the exciting possibility of using a biomaterial to deliver stem cells to a very specific location in the brain. It is too early to say if it will be clinically effective in patients but the more we explore these possibilities the more likely it is that we will develop successful therapies."

Two distinct molecular pathways can make regulatory immune cells

Finding a way to bypass the molecular events involved in autoimmunity - where the body's immune system mounts a self-directed attack - could lead to new treatments for autoimmune disorders and chronic infections. A study published in this week's issue of PLoS Biology describes genetic evidence that two distinct molecular pathways control the formation of regulatory T cells (Treg), a cell type vitally important in limiting undesirable immune responses.

Treg cells are like the peace-keepers of the immune defence system - they limit the actions of effector T cells, the foot-soldiers of the body. If the body lacks sufficient numbers of Treg cells, it loses the ability to tone down immune responses once invading pathogens are cleared. In addition, the body is unable to suppress T cell responses that recognize and target the body itself. The latter can lead to autoimmunity, which can destroy vital tissues and organs.

Under normal healthy conditions, the majority of Treg cells are derived from an organ called the thymus. New work from researchers at Cincinnati Children's Hospital Medical Center and The Scripps Research Institute in California, shows that if a gene called Carma1 isn't expressed normally, Treg development is impaired in the thymus. Mutations in Carma1 can result in a failure of the thymus to produce Treg cells, said senior investigator Kasper Hoebe, Ph.D., a researcher at Cincinnati.

But the study also points to a second molecular pathway - occurring in the peripheral lymphoid system - that is known to result in development of Treg cells. This means if the process in the thymus breaks down, as in the case with Carma1 mutations, Treg cells created in the peripheral lymphoid system can compensate.

"We show that the two pathways for Treg development are molecularly distinct, and Treg can arise quite well in the peripheral lymphoid system, via mechanisms that are independent of the thymic process," Dr. Hoebe said. "This is important because it shows the flexibility of the immune system to regulate T cell responses. If we understand the molecular requirements of these pathways we can potentially use these as targets for therapeutic intervention - which is the eventual goal."

Possible therapies may include the ability to repress the self-destructive immune response in autoimmune disease by increasing Treg development, or achieving the opposite effect to treat chronic infectious diseases - inhibiting Treg development and promoting activation of destructive T cells.

More information: Barnes MJ, Krebs P, Harris N, Eidenschenk C, Gonzalez-Quintial R, et al. (2009) Commitment to the regulatory T cell lineage requires CARMA1 in the thymus but not in the periphery. PLoS Biol 7(3): e1000051. doi:10.1371/journal.pbio.1000051, http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.1000051

Source: Public Library of Science

Un médicament améliore la marche de patients atteints de sclérose en plaques

PARIS (AFP) — Un médicament améliore la marche chez des malades atteints de sclérose en plaques et semble bien toléré, selon les résultats d'un essai clinique sur 300 personnes publiés vendredi dans la revue médicale The Lancet.

L'essai clinique de phase III (dernière étape avant la demande de mise sur le marché) a été conduit par Andrew Goodman (université de Rochester, New York) et ses collègues dans 33 centres de lutte contre la sclérose en plaques (SEP) aux Etats-Unis et au Canada.

301 personnes atteintes de SEP, âgées entre 18 et 70 ans, ont reçu pendant 14 semaines soit le médicament fampridine (10 mg deux fois par jour), soit un placebo.

La proportion des malades dont la vitesse de marche s'est améliorée était nettement supérieure dans le groupe traité avec la fampridine (35%) que dans le groupe témoin ayant reçu le placebo (8%), selon les résultats de cet essai.

La SEP, maladie neurologique particulièrement invalidante, provoque une dégradation de la gaine de myéline qui protège les fibres nerveuses (cerveau, moelle épinière et nerf optique), ce qui ralentit la vitesse de conduction de l'influx nerveux.

Cette maladie chronique, qui touche le plus souvent le jeune adulte, concerne quelque 80.000 personnes en France et 350.000 en Europe.

La fampridine n'agit pas sur le processus de démyélinisation mais contribue à améliorer la transmission de l'influx nerveux.

La société Acorda Therapeutics, qui a développé ce traitement, a déposé ce mois-ci une demande d'autorisation de mise sur le marché auprès de l'Agence américaine des médicaments (FDA).

Obtention de cellules souches neuronales

Des chercheurs de l'Université (Une université est un établissement d'enseignement supérieur dont l'objectif est la production du savoir (recherche),...) de Bonn ont réussi à obtenir des cellules souches neuronales à partir de cellules souches embryonnaires humaines.

Ces cellules présentent l'intérêt non seulement de pouvoir se conserver presque sans limite dans une culture (La définition que donne l'UNESCO de la culture est la suivante [1] :), mais également de servir de source presque inépuisable pour différents types de cellules nerveuses. Cette recherche (La recherche scientifique désigne en premier lieu l’ensemble des actions entreprises en vue de produire et de...) a aussi permis de démontrer que ces cellules nerveuses peuvent s'intégrer dans les circuits neuronaux du cerveau.

L'étude est publiée dans la prochaine édition de Proceedings of the National Academy of Sciences PNAS (doi: 10.1073/pnas.0808387106).


Pendant des années, la recherche sur les cellules souches a semblé divisée en deux mondes: les cellules sources embryonnaires au développement illimité d'une part, et les cellules souches somatiques qui peuvent être obtenues à partir de tissus d'adultes, mais ces dernières cellules étaient limitées dans leur potentiel de développement.

Les scientifiques de l'Université de Bonn ont rapproché ces deux mondes en créant des cellules souches du cerveau pouvant se multiplier et se conserver quasiment indéfiniment. C'est à partir de ces cellules que les chercheurs ont pu obtenir différentes cellules nerveuses dont des semblables à celles observées dans la maladie de Parkinson.

L'expérimentation (L'expérimentation est une méthode scientifique qui consiste à tester par des expériences répétées la validité d'une...) sur des animaux a prouvé que ces cellules nerveuses obtenues artificiellement fonctionnaient bien. Les cellules transplantées sur des souris de laboratoire sont entrées en contact avec le cerveau du receveur pouvant émettre des signaux et en recevoir. Les chercheurs veulent utiliser cette source quasi inépuisable de cellules nerveuses humaines pour faire des études sur les maladies neuro-dégénératives.

Source: communiqué de presse de l'Université de Bonn
Illustration: Wikipédia