Breaking research demonstrates that running in brain-damaged mice triggers the production of a molecule that repairs brain tissue and extends their lifespan. The investigators hope that the findings could lead to innovative treatments for certain neurodegenerative disorders.

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A study investigating brain-damaged mice finds that running reduces the deficit.

As with most physical activities, running is known to hold a range of health benefits.

However, breaking research finds that, in a certain type of mouse, running has a significant beneficial impact on brain health.

Although the findings are specific to a single strain of mouse and cannot yet be scaled up to humans, they open an interesting new avenue of research.

A team of researchers from the Ottawa Hospital and the University of Ottawa in Canada ran trials on Snf2h-null ataxic mice.

These mice are born with a particularly small cerebellum, a part of the brain important for balance and coordination.

Because of the deficits in their brains, these mice find it difficult to balance themselves and have a shorter lifespan – just 25 to 40 days.

The researchers allowed some of the mice the opportunity to run by installing a wheel into their cages. Surprisingly, the mice given the opportunity to run lived more than 12 months (a relatively normal lifespan for a mouse).

On top of their extended lives, the running mice also put on more weight and achieved a better sense of balance, compared with their less active siblings.

We saw that the existing neurons became better insulated and more stable. This means that the unhealthy neurons worked better and the previously damaged circuits in the brain became stronger and more functional.”

Dr. Matías Alvarez-Saavedra, lead author

However, these changes were reversed if the opportunity to exercise was taken away. Once the running wheel was removed, the symptoms returned, and their lives were once more cut short.

When the nervous systems of the running and resting mice were inspected and compared, the researchers found clear differences. The neurons in the cerebellum of the exercised mice showed an increase in myelin.

Myelin is a white, lipid-based substance that coats the majority of nerve fibers; it acts in a similar way to electrical insulation on cables. Without it, nerves cannot carry their messages as quickly or efficiently.

Once the team had observed the increased myelination, they needed to understand what molecules were driving this renewed production of insulation. To this end, the team investigated the differences in gene expression between the two mice.

A genetic deep-dive produced a prime candidate – a substance called VGF, which is a nerve growth factor known to influence synaptic plasticity and metabolism. It is just one of hundreds of molecules that the brain and muscles release during exercise. VGF appears to have an antidepressant effect and helps make exercise feel good.

To test whether VGF could be the molecule that induced the positive effects in the mice, the team devised another arm to their study. They used a non-replicating virus to introduce the VGF protein into the bloodstream of mice without access to a running wheel.

This introduction of VGF showed a similar response to running – there was more insulation in the damaged areas of the cerebellum and fewer disease symptoms.

These fascinating findings, published this week in Cell Reports, open up the possibility of a novel approach to treating neurodegenerative diseases that involve a loss of myelin.

Dr. Picketts, senior author of the paper and a senior scientist at the Ottawa Hospital and professor at the University of Ottawa, says: “What is clear is that VGF is important to kick-start healing in damaged areas of the brain.” He continues: “We need to do broader research to see whether this molecule can also be helpful in treating multiple sclerosis and other neurodegenerative diseases.”

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