Exercise Those Brain Genes

So, how does exercise work in changing the brain? Is it only an indirect effect of a better brain "environment"? Of course, the brain loves to be in a "healthy" environment. In fact, the healthier the better - and physical exercise (PE) and its effects on controlling the fats and the sugars and optimizing brain oxygenation through good blood flow and pressure - would clearly have a major role in "optimizing" the environment.

But is this the whole story? Here is the great news: maybe not. One of the most exciting hypotheses is that PE might have a direct effect on the brain. My colleagues at Yale University (1) have shown that mice spending their time running on training wheels turn on brain genes that are responsible for the production of a number of neurotrophic and growth factors, including VGF, a neuropeptide precursor involved in energy balance, and neuritin, an immediate early gene involved in neuroplasticity. These are all proteins that keep the brain going and possibly also growing. Same genes were simply silent in the comparator group of sedentary mice. Moreover, the action of one gene in particular - VGF - while greatly enhanced by exercise, has also been shown to have a powerful anti-depressant effect, while blocking VGF inhibited the effects of exercise and induced depressive-like behavior in the mice.

A few important take home points: the mice joggers were not joking around - they were really running, covering an average of 4-6 miles (10 km) a day. The genetic effects were reported after about 4 weeks of such - rather intense (at least by human standards) - exercise, which is consistent with other studies. We know that mice, given on opportunity, love to run, and these mice were indeed given the opportunity (i.e. unrestricted access to a running wheel that they can us as much or as little as they wanted). Also, they were doing it because they wanted to (i.e. they were not forced to exercise)!

Now, any such study raises a number of "human comparisons" questions. For us humans 6 miles a day might be a lot, but is that true when it comes to mice? In a cat running after a mouse world is 6 miles a day a lot or just what's expected? Also, is that what a mouse would do anyway, even in their wild, natural environment or running all day long only happens when they live in a cage, bored to death, with nothing else to do? And, more importantly, how does 6 mice miles compare with human miles? Finally, is it really that PE is the proximal cause or is PE just one event from a cascade (e.g. an "intellectual gratification" activity) of events that eventually results in the reported effects?

My two cents: while these are important questions this landmark study suggests that when it comes to PE and the brain, while the old claim that "what's good for the body is also good for the mind" is true, there is so much more to the story. Now, when someone says "exercise that brain" you actually have a reason to exercise it as hard as you can as in "Aaah, what do you mean, really?"

(1) http://www.nature.com/nm/journal/v13/n12/pdf/nm1669.pdf

© Copyright Adrian Preda, M.D.