Myelin

 Running triggers production of a molecule that repairs the brain in animal models

Posted by

0


Running triggers production of a molecule that repairs the brain in animal models
Researchers at the Ottawa Hospital and the University of Ottawa have discovered that a molecule triggered by running can help repair certain kinds of brain damage in animal models. The team includes (from left) Dr. Rashmi Kothary, Dr. Robin Parks, Yves De Repentigny, Keqin Yan and Dr. David Picketts. 

Researchers at The Ottawa Hospital and the University of Ottawa have discovered that a molecule triggered by running can help repair certain kinds of brain damage in animal models. They found that this molecule, called VGF nerve growth factor, helps to heal the protective coating that surrounds and insulates nerve fibres. Their study, published in Cell Reports, could pave the way for new treatments for multiple sclerosis and other neurodegenerative disorders that involve damaged nerve insulation.

 However, if these mice were given the opportunity to run freely on a wheel, they lived over 12 months, a more typical mouse lifespan. The running mice also gained more weight and acquired a better sense of balance compared to their sedentary siblings. However, they needed to keep exercising to maintain these benefits. If the running wheel was removed, their symptoms came back and they did not live as long.

Looking at their brains, the researchers found that the running mice gained significantly more insulation in their cerebellum compared to their sedentary siblings.

To find out why running was causing this insulation, the team looked for differences in gene expression between the running and sedentary mice and identified VGF as a prime candidate. VGF is one of the hundreds of molecules that muscles and the brain release into the body during exercise. It also has an anti-depressant effect that helps make exercise feel good.

When the research team used a non-replicating virus to introduce the VGF protein into the bloodstream of a sedentary mutant mouse, the effects were similar to having the mouse run – more insulation in the damaged area of the cerebellum, and fewer disease symptoms.

“We saw that the existing neurons became better insulated and more stable,” said Dr. Matías Alvarez-Saavedra, the lead author on the paper. “This means that the unhealthy neurons worked better and the previously damaged circuits in the brain became stronger and more functional.”

Dr. Alvarez-Saavedra obtained his PhD in Dr. Picketts’ research group, and is currently a postdoctoral fellow at the New York University School of Medicine and the Howard Hughes Medical Institute.

“We need to do broader research to see whether this molecule can also be helpful in treating and other neurodegenerative diseases,” said Dr. Picketts.

 

Highlights

  • •Running promotes the survival of mice with cerebellar ataxia following Snf2h inactivation
  • •Running ataxic mice show enhanced oligodendrogenesis and de novo myelination
  • •Comparative RNA-seq studies identify VGF as a contributor to brain repair
  • •VGF overexpression improves ataxic phenotype in mice without exercise

Summary

Exercise has been argued to enhance cognitive function and slow progressive neurodegenerative disease. Although exercise promotes neurogenesis, oligodendrogenesis and adaptive myelination are also significant contributors to brain repair and brain health. Nonetheless, the molecular details underlying these effects remain poorly understood. Conditional ablation of the Snf2h gene impairs cerebellar development producing mice with poor motor function, progressive ataxia, and death between postnatal days 25–45. Here, we show that voluntary running induced an endogenous brain repair mechanism that resulted in a striking increase in hindbrain myelination and the long-term survival of Snf2h cKO mice. Further experiments identified the VGF growth factor as a major driver underlying this effect. VGF neuropeptides promote oligodendrogenesis in vitro, whereas Snf2h cKO mice treated with full-length VGF-encoding adenoviruses removed the requirement of exercise for survival. Together, these results suggest that VGF delivery could represent a therapeutic strategy for cerebellar ataxia and other pathologies of the CNS.

Sleep ‘boosts brain cell numbers’

Posted by

0


Scientists believe they have discovered a new reason why we need to sleep – it replenishes a type of brain cell.

Sleep ramps up the production of cells that go on to make an insulating material known as myelin which protects our brain’s circuitry.

_69607872_synapses,_artwork-spl-1

The findings, so far in mice, could lead to insights about sleep’s role in brain repair and growth as well as the disease MS, says the Wisconsin team.

The work is in the Journal of Neuroscience.

Dr Chiara Cirelli and colleagues from the University of Wisconsin found that the production rate of the myelin making cells, immature oligodendrocytes, doubled as mice slept.

The increase was most marked during the type of sleep that is associated with dreaming – REM or rapid eye movement sleep – and was driven by genes.

In contrast, the genes involved in cell death and stress responses were turned on when the mice were forced to stay awake.

Precisely why we need to sleep has baffled scientists for centuries. It’s obvious that we need to sleep to feel rested and for our mind to function well – but the biological processes that go on as we slumber have only started to be uncovered relatively recently.

Growth and repair

Dr Cirelli said: “For a long time, sleep researchers focused on how the activity of nerve cells differs when animals are awake versus when they are asleep.

_69630898_matthew

“Now it is clear that the way other supporting cells in the nervous system operate also changes significantly depending on whether the animal is asleep or awake.”

The researchers say their findings suggest that sleep loss might aggravate some symptoms of multiple sclerosis (MS), a disease that damages myelin.

In MS, the body’s immune system attacks and destroys the myelin coating of nerves in the brain and spinal cord.

Future studies could look at whether or not sleep affects the symptoms of MS, says Dr Cirelli.

Her team is also interested in testing whether lack of sleep, especially during adolescence, may have long-term consequences for the brain.

Sleep appears necessary for our nervous systems to work properly, says the US National Institute of Neurological Disorders and Stroke (NINDS).

Deep sleep coincides with the release of growth hormone in children and young adults. Many of the body’s cells also show increased production and reduced breakdown of proteins during deep sleep.

Since proteins are the building blocks needed for cell growth and for repair of damage from factors like stress and ultraviolet rays, deep sleep may truly be “beauty sleep”, says NINDS.

Source:BBC

MS damage repair treatment looked at by Edinburgh researchers.

Posted by

0


New treatments that could help slow the progression of multiple sclerosis could be a step closer due to research by Edinburgh University.

In MS patients the protective layer around nerve cells in the brain, known as myelin, is broken down.

Scientists have discovered that immune cells, known as macrophages, help trigger the regeneration of myelin.

The researchers hope their work could eventually lead to the development of new drugs.

The sheath around nerves cells, made of myelin, is destroyed in MS, leaving the nerves struggling to pass on messages.

_67989720_c0020395-synapses,_artwork-spl

This leads to problems with mobility, balance and vision. There is no cure but current treatments concentrate on limiting the damage to myelin.

‘Stripped away’

Now the team at Edinburgh University has found that the immune cells, known as macrophages, can release a compound called activin-A, which activates production of more myelin.

Dr Veronique Miron, from the Medical Research Council Centre for Regenerative Medicine at the university, said: “In multiple sclerosis patients, the protective layer surrounding nerve fibres is stripped away and the nerves are exposed and damaged.

 “Start Quote

We look forward to seeing this research develop further”

Dr Susan Kohlhaas MS Society

“Approved therapies for multiple sclerosis work by reducing the initial myelin injury – they do not promote myelin regeneration.

“This study could help find new drug targets to enhance myelin regeneration and help to restore lost function in patients with multiple sclerosis.”

The study, which looked at myelin regeneration in human tissue samples and in mice, was funded by the MS Society, the Wellcome Trust and the Multiple Sclerosis Society of Canada.

The findings are published in Nature Neuroscience.

Scientists now plan to start further research to look at how activin-A works and whether its effects can be enhanced.

Dr Susan Kohlhaas, head of biomedical research at the MS Society, said: “We urgently need therapies that can help slow the progression of MS and so we’re delighted researchers have identified a new, potential way to repair damage to myelin.

“We look forward to seeing this research develop further.”

Source:BBC