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Exercise for Stress-Induced Depression

We all know by now how healthy regular physical activity is. We also know that it's one of the best anti-depressants known, and there are various reasons for its benefits. First are the endorphins, those compounds produced in our body that act as effective pain-killers and responsible for the “runner’s high.” Next, came the endocannabinoids, the pleasure-inducing molecules released during hard exercise that provide benefits to numerous body systems, including the brain.

Now, decades after scientists first speculated on the effects of exercise on the brain, researchers have discovered a new reason to get active: exercise not only feels good, it protects the brain from depression.

In these newer mouse studies, the scientists showed that changes in skeletal muscles, incurred through exercise helped rid the body of a stress-induced amino acid called kynurenine that has been associated with mental illness.

“Our initial research hypothesis was that trained muscle would produce a substance with beneficial effects on the brain,” said the principal investigator. “We actually found the opposite: well-trained muscle produces an enzyme that purges the body of harmful substances. So in this context the muscle’s function is reminiscent of that of the kidney or liver.”

The scientists developed a genetically-engineered mouse strain with high levels of PGC-1(alpha)1 (a metabolic regulator, which would link these results to the mitochondria), which resulted in "muscled-up" mice. These mice, as well as a group of normal unmodified mice, were then exposed to five weeks of a highly stressful environment of noises and flashing lights. After the five weeks, the normal mice showed evidence of depressed behavior, including lethargy and disinterest in food, but the genetically-engineered mice did not.

The reason, the scientists believe, was that the engineered mice also had higher-than-normal levels of an enzyme called KAT, which, under stress, converts kynurenine into kynurenic acid, which cannot cross the blood-brain barrier. In effect, KAT in these muscled-up mice prevented stress-related neurochemicals from entering the brain.

“It’s possible that this work opens up a new pharmacological principle in the treatment of depression, where attempts could be made to influence skeletal muscle function instead of targeting the brain directly,” the researchers said. “Skeletal muscle (when activated) can protect the brain from insults and related mental illness.”

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Source: Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression

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