Matter of chemistry

Melissa Healy

Tuesday, September 30, 2014

Using mice that were stressed to the point where depression would be a predictable response, researchers at Sweden's Karolinska Institute in Stockholm uncovered a series of biochemical events that begins with exercise and ends with mice that are resilient to stress.

Their findings, published last week in the journal Cell, not only illuminate the link between chronic stress and depression; they help explain how a known anti-depressive agent - in this case exercise - works to prevent or mitigate the debilitating mental condition.

That is more than can be said for many antidepressant medications, which clearly help many with depression, but whose mechanism of action is not all that well understood.

The findings also point the way to a novel way to ward off depression. Antidepressant medications seem to rely largely on changing brain chemistry, and they require the use of molecules that cross the barrier that protects the brain against most blood- borne toxins.

But the Swedish researchers found that exercise's therapeutic effects begin in the muscles, and alter brain chemistry only indirectly.

Finding a way to mimic exercise's antidepressant effect could also be of "great therapeutic value" to patients who are not helped by antidepressants or who find hard exercise difficult, the authors suggested. "It will be interesting to expand this study design to a larger cohort of human volunteers, to include also patients with depression," the authors wrote.

Here's what research, gleaned from wheel-running mice and from muscle biopsies of exercising humans, has uncovered about the mechanism by which exercise can prevent and chase away the blues in people under stress:

Within the muscles, endurance-type exercise prompts the activation of a protein called PGC-1a1.

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Matter of chemistry