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Spokane, Washington  Est. May 19, 1883

Study links exercise, mental wellness

Melissa Healy Los Angeles Times

We all know that lacing up and breaking a sweat is good for our mood, and that exercise can feel like a lifeline when the stresses of life threaten to engulf us. But how a pounding workout helps lift us from the encroaching gloom was a mystery – until now.

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 cascade of biochemical events that begins with exercise and ends with mice that are unusually resilient in the face of stress.

Their findings, published Thursday 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’s 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 in those under stress. 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.

Explaining the exact cascade of events that begins with endurance exercise won’t be easy. Here’s what new research, gleaned both from wheel-running mice and from muscle biopsies of exercising humans, has uncovered about the mechanism by which exercise can prevent and even chase away the blues in people under stress:

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

The authors of the latest study show that activating PGC-1a1 in the muscles increases the production of kynurenine aminotransferases inside of muscle. And the presence of these enzymes catalyzes a chemical change in kynurenine, converting it into kynurenic acid.

In mice, and very likely in humans too, chronic stress increase levels of kynurenine in the brain – and high levels of kynurenine appear to induce depression. But kynurenic acid can’t get into the brain because it can’t get across the blood-brain barrier. So, when PGC-1a1 levels in muscle are high, and kynurenine gets converted into kynurenic acid, levels of kynurenine in the brain naturally drop.

The result: mental wellness in the face of disadvantage, social setbacks and general adversity.