How Your Daily Run Protects Against Stress-Induced Depression

Getting more physical activity is often a suggestion for relieving some of the symptoms of depression. It is also a good stress-reliever. But how?

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Getting more physical activity is often a suggestion for relieving some of the symptoms of depression. It is also a good stress-reliever. But how? Until now, the mechanisms that mediate this protective effect have not been well understood.

In a new animal study, researchers at Karolinska Institutet in Sweden found that exercise training induces changes in skeletal muscle that purges the blood of a harmful substance that accumulates during stress.

Currently, most antidepressant medications are focused on brain chemicals such as serotonin as it is thought that low serotonin levels lead to symptoms of depression. However, “in neurobiological terms, we actually still don’t know what depression is,” says Mia Lindskog, researcher at the Department of Neuroscience.

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Lindskog and a team of scientists focused on a protein known as PGC-1a1 which increases in skeletal muscle during exercise. Mice with high levels of this compound were exposed to a stressful environment, which included loud noises, flashing lights and irregular circadian rhythms (poor sleep quality). These mice were better able to adapt without the presence of depressive symptoms, unlike “normal” mice which had developed depressive behaviors.

The genetically modified PgC-1a1 mice had higher levels of an enzyme that purges the body of harmful substances, says Jorge Ruas, principle investigator at the Department of Physiology and Pharmacology. The enzyme, known as KAT, converts a substance known as kynurenine (known to be found at high levels in patients with mental illness) into kynurenic acid. This appears to be especially protective in that it prevents the brain from being damaged during stress because kynurenic acid cannot cross the blood-brain barrier.

“Skeletal muscle appears to have a detoxification effect that, when activated, can protect the brain from insults and related mental illness," says Ruas.

Journal Reference:
Maria Lindskog, and Jorge L. Ruas et al. Skeletal Muscle PGC-1a1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression. Cell, September 2014

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