Cambridge scientists reverse ageing process in rat brain stem cells

Anonymous — Wed, 14 Aug 2019 17:01:45 +0000

̽��ֱ��results, published today in Nature, have far-reaching implications for how we understand the ageing process, and how we might develop much-needed treatments for age-related brain diseases.

As our bodies age, our muscles and joints can become stiff, making everyday movements more difficult. This study shows the same is true in our brains, and that age-related brain stiffening has a significant impact on the function of brain stem cells.

A multi-disciplinary research team, based at the Wellcome-MRC Cambridge Stem Cell Institute at the ̽��ֱ�� of Cambridge, studied young and old rat brains to understand the impact of age-related brain stiffening on the function of oligodendrocyte progenitor cells (OPCs). These cells are a type of brain stem cell important for maintaining normal brain function, and for the regeneration of myelin – the fatty sheath that surrounds our nerves, which is damaged in multiple sclerosis (MS). ̽��ֱ��effects of age on these cells contributes to MS, but their function also declines with age in healthy people.

To determine whether the loss of function in aged OPCs was reversible, the researchers transplanted older OPCs from aged rats into the soft, spongy brains of younger animals. Remarkably, the older brain cells were rejuvenated, and began to behave like the younger, more vigorous cells.

To study this further, the researchers developed new materials in the lab with varying degrees of stiffness, and used these to grow and study the rat brain stem cells in a controlled environment. ̽��ֱ��materials were engineered to have a similar softness to either young or old brains.

To fully understand how brain softness and stiffness influences cell behavior, the researchers investigated Piezo1 – a protein found on the cell surface, which informs the cell whether the surrounding environment is soft or stiff.

Dr Kevin Chalut, who co-led the research, said: “We were fascinated to see that when we grew young, functioning rat brain stem cells on the stiff material, the cells became dysfunctional and lost their ability to regenerate, and in fact began to function like aged cells. What was especially interesting, however, was that when the old brain cells were grown on the soft material, they began to function like young cells – in other words, they were rejuvenated.”

“When we removed Piezo1 from the surface of aged brain stem cells, we were able to trick the cells into perceiving a soft surrounding environment, even when they were growing on the stiff material,” explained Professor Robin Franklin, who co-led the research with Dr Chalut. “What’s more, we were able to delete Piezo1 in the OPCs within the aged rat brains, which lead to the cells becoming rejuvenated and once again able to assume their normal regenerative function.”

Dr Susan Kohlhaas, Director of Research at the MS Society, who part funded the research, said: “MS is relentless, painful, and disabling, and treatments that can slow and prevent the accumulation of disability over time are desperately needed. ̽��ֱ��Cambridge team’s discoveries on how brain stem cells age and how this process might be reversed have important implications for future treatment, because it gives us a new target to address issues associated with aging and MS, including how to potentially regain lost function in the brain.”

This research was supported by the European Research Council, MS Society, Biotechnology and Biological Sciences Research Council, ̽��ֱ��Adelson Medical Research Foundation, Medical Research Council and Wellcome.

Niche stiffness underlies the ageing of central nervous system progenitor cells, M. Segel, B. Neumann, M. Hill, I. Weber, C. Viscomi, C. Zhao, A. Young, C. Agley, A. Thompson, G. Gonzalez, A. Sharma, S. Holmqvist, D. Rowitch, K. Franze, R. Franklin and K. Chalut is published in Nature.

New research reveals how increasing brain stiffness as we age causes brain stem cell dysfunction, and demonstrates new ways to reverse older stem cells to a younger, healthier state.

...when the old brain cells were grown on the soft material, they began to function like young cells – in other words, they were rejuvenated

Kevin Chalut

Mikey Segel

Aged rat brain stem cells grown on a soft surface (right) show more healthy, vigorous growth than similar aged brain stem cells grown on a stiff surface (left). ̽��ֱ��red marker shows brain stem cells, and the green marker indicates cell proliferation.

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Vitamin D could repair nerve damage in multiple sclerosis, study suggests

cjb250 — Mon, 07 Dec 2015 14:00:25 +0000

Researchers, from the MS Society Cambridge Centre for Myelin Repair, identified that the ‘vitamin D receptor’ protein pairs with an existing protein, called the RXR gamma receptor, already known to be involved in the repair of myelin, the protective sheath surrounding nerve fibres.

By adding vitamin D to brain stem cells where the proteins were present, they found the production rate of oligodendrocytes (myelin making cells) increased by 80%. When they blocked the vitamin D receptor to stop it from working, the RXR gamma protein alone was unable to stimulate the production of oligodendrocytes.

In MS, the body’s own immune system attacks and damages myelin, causing disruption to messages sent around the brain and spinal cord; symptoms are unpredictable and include problems with mobility and balance, pain, and severe fatigue. ̽��ֱ��body has a natural ability to repair myelin, but with age this becomes less effective.

Professor Robin Franklin from the MS Society Cambridge Centre for Myelin Repair and the Wellcome Trust-Medical Research Council Stem Cell Institute, who led the study, says: “For years scientists have been searching for a way to repair damage to myelin. So far, the majority of research on vitamin D has looked at its role in the cause of the disease. This work provides significant evidence that vitamin D is also involved in the regeneration of myelin once the disease has started. In the future we could see a myelin repair drug that works by targeting the vitamin D receptor.”

Dr Susan Kohlhaas, Head of Biomedical Research at the MS Society, said: “More than 100,000 people in the UK have multiple sclerosis and finding treatments that can slow, stop or reverse the worsening of disability is a priority for the MS Society. We’d now like to see more studies to understand whether taking vitamin D supplements could, in time, be an effective and safe treatment for people with MS.

She continued: “For now though, this is early stage research that’s been done in the laboratory and more work is needed before we know whether it would hold true in people with MS. It’s not a good idea, however, to be deficient in vitamin D and we’d encourage anybody who thinks they might be to speak to their GP.”

Following this research, scientists will need to understand more about the underlying biology of this receptor before considering how the vitamin D receptor could be safely and effectively targeted in future trials in people with MS.

Reference
Guzman de la Fuente, A et al. Vitamin D receptor–retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation. Journal of Cell Biology; 7 Dec 2015

Adapted from a press release by the MS Society

A protein activated by vitamin D could be involved in repairing damage to myelin in people with multiple sclerosis (MS), according to new research from the ̽��ֱ�� of Cambridge. ̽��ֱ��study, published today in the Journal of Cell Biology, offers significant evidence that vitamin D could be a possible treatment for MS in the future.

This work provides significant evidence that vitamin D is involved in the regeneration of myelin once the disease has started

Robin Franklin

Andrew c

Neuron with oligodendrocyte and myelin sheath (edited)

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Cambridge scientists reverse ageing process in rat brain stem cells

Vitamin D could repair nerve damage in multiple sclerosis, study suggests