A molecule triggered by running can help repair certain
kinds of brain damage in animal models, revealed researchers at The Ottawa Hospital and the University of Ottawa. They found that this molecule,
called VGF nerve growth factor, helps to heal the protective coating
that surrounds and insulates nerve fibers.
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.
‘A molecule, called VGF nerve growth factor, is triggered by running and can help repair certain kinds of brain damage in animal models.’
"We are excited by this discovery and now plan to uncover the
molecular pathway that is responsible for the observed benefits of VGF,"
said Dr. Picketts, senior author of the paper and a senior scientist at
The Ottawa Hospital and professor at the University of Ottawa. "What is
clear is that VGF is important to kick-start healing in damaged areas
of the brain."
The team made this discovery while studying mice genetically
modified to have a small cerebellum, the part of the brain that controls
balance and movement. These mice had trouble walking and lived only 25
to 40 days.
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
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 multiple sclerosis and other
neurodegenerative diseases," said Dr. Picketts.