Physical exercise could protect the brain from stress-induced depression, according to a recent study.

Researchers found that exercise training induces changes in skeletal muscle that can purge the blood of a substance that accumulates during stress, and is harmful to the brain.

"In neurobiological terms, we actually still don't know what depression is. Our study represents another piece in the puzzle, since we provide an explanation for the protective biochemical changes induced by physical exercise that prevent the brain from being damaged during stress," Mia Lindskog,, researcher at the Department of Neuroscience at Karolinska Institute, said in a statement.

It was known that the protein PGC-1a1 (pronounced PGC-1alpha1) increases in skeletal muscle with exercise, and mediates the beneficial muscle conditioning in connection with physical activity. In this study researchers used a genetically modified mouse with high levels of PGC-1a1 in skeletal muscle that shows many characteristics of well-trained muscles (even without exercising).

For the study, these mice, and normal control mice, were exposed to a stressful environment, such as loud noises, flashing lights and reversed circadian rhythm at irregular intervals. After five weeks of mild stress, normal mice had developed depressive behavior, whereas the genetically modified mice (with well-trained muscle characteristics) had no depressive symptoms.

"Our initial research hypothesis was that trained muscle would produce a substance with beneficial effects on the brain. 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 the liver," Jorge Ruas, principal investigator of the study, said in a statement.

The researchers discovered that mice with higher levels of PGC-1a1 in muscle also had higher levels of enzymes called KAT. KATs convert a substance formed during stress (kynurenine) into kynurenic acid, a substance that is not able to pass from the blood to the brain. The exact function of kynurenine is not known, but high levels of kynurenine can be measured in patients with mental illness. In this study, the researchers demonstrated that when normal mice were given kynurenine, they displayed depressive behavior, while mice with increased levels of PGC-1a1 in muscle were not affected.

The findings were recently published in the journal Cell.