That Eureka! Moment

"We never would have expected that exercise would make these mice survive for so much longer."
"This has opened up a whole new avenue of research for us. It really shows how discovery science can lead to new translational [research]."
"Most basic scientists will follow the leads that appear, and you need good funding for that."
Dr. David Picketts, senior scientist, The Ottawa Hospital

"We saw that the existing neurons became better insulated and more stable."
Matias Alvarez-Saavedra, post-doctoral fellow, New York University School of Medicine

Runners at the start of the 2013 Ottawa Marathon. Researchers at The Ottawa Hospital and the University of Ottawa have discovered that running triggers production of a molecule that helps repair the brain. In mice at least. ( Fred Chartrand/Canadian Press)

When then-PhD student Matias Alvarez-Saavedra worked alongside Dr. Picketts, a professor at the University of Ottawa, among items being focused on at the research laboratory was a study on the role of proteins in brain development and intellectual-disability disorders. Mice at the lab were genetically developed, born with small cerebellums, that part of the brain controlling balance and movement. Their genetic outcome led to difficulty in walking and the longevity of the affected mice was between 25 to 40 days.

The doctoral student decided he would try something different, placing running wheels in the cages holding these genetically modified mice. The mice used those running wheels and because the mice freely ran on them, exercising their bodies, their brains were also affected. These mice demonstrated that a significant change was taking place as a result of their running; they lived for over 12 months, representing a typical lifespan for a normal mouse.

They also gained weight, acquiring in the entire process an improved sense of balance, as opposed to the mice that hadn't any opportunity to run. Significantly, when the running wheel was removed from their cages, the symptoms that gave the mice difficulty in balance resulting in shortened life-spans, returned. This experiment, a kind of 'research in motion' led to the study focusing on what had been occurring.

New research shows mice with smaller cerebellums that are given the opportunity to run freely live much longer than sedentary ones. (Robert F. Bukaty/Associated Press)

And it was discovered that what had occurred was that running triggered production of a molecule, VGF growth factor, whose function is to aid in healing the protective coating around nerve fibres. The study and its conclusions, was recently published in Cell Reports. What Dr. Picketts, senior author of the study thought, was that Matias Alvarez-Saavedra might re-introduce the manipulated gene back into the mice in support of the finding that its removal had caused the small cerebellums.

Rather than do that, Alvarez-Saavedra, the paper's lead author, thought of the running wheels. Perhaps not all that far-fetched, given the widely acknowledged benefits of exercise. Still, what that represented was a process not yet clearly understood. Now it is accepted that the VGF research has aided scientists to more clearly understand the health benefits produced in mice when they were given the opportunity to run.

A closer investigation resulted in an understanding that the mice that ran gained vitally increased insulation around their neurons which in turn encouraged the neurons to become more effective and efficient. When it was understood what had happened, the research shifted to a new direction, reflecting a scientific curiosity reflective of basic research. And the conclusion was that running spurs production of a molecule capable of repairing some elements of brain damage.

Understanding this process leads to hope for multiple sclerosis patients, stroke patients and more. So it is understandable that the study was funded by the Canadian Institutes of Health Research along with funding from the Multiple Sclerosis Society of Canada and the Canadian Partnership for Stroke Recovery, into further investigations of VGF.