Did you know that physical exercise has many beneficial effects on human health including the protection from stress-induced depression? Its true however, until now the mechanisms that mediate this protective effect have been unknown.
A new study using mice researchers show that exercise training induces changes in skeletal muscles that can purge the blood of a substance that accumulates during stress and is harmful to the brain.
The study conducted by researchers at the Karolinska Institutent in Sweden and published in the journal Cell 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. It was known that the protein PGC-1a1 increases in skeletal muscle with exercise and mediates the beneficial muscle conditioning in connection with physical activity. The mice along with normal control mice were exposed to a stressful environment that included loud noises, flashing lights and reversed circadian rhythm at irregular intervals. Following five weeks of mild stress the normal mice had developed depressive behavior whereas the genetically-modified mice with well-trained muscle characteristics had no depressive symptoms.
For the study 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. These animals never show elevated kynurenine levels in their blood since the KAT enzymes in their well-trained muscles quickly convert it to kynurenic acid which results in a protective mechanism.
What The Researchers Discovered
Mice with higher levels of PGC-1a1 in muscle also had higher levels of enzymes called KATs. KATs convert a substance formed during stress 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 kynurenine can be measured in patients with mental illness.
In neurobiological terms, we actually still dont know what depression is, said researcher Mia Lindskog of the Department of Neuroscience at Karolinska Institutent. 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.
Our initial research hypothesis was that trained muscle would produce a substance with beneficial effects on the brain, added principal investigator Jorge Ruas. We actually found the opposite well-trained muscle produces an enzyme that purges the body of a harmful substance. So in this context the muscles function is reminiscent of that of the kidney or the liver. Its 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. Skeletal muscle appears to have a detoxification effect that when activated can protect the brain from insults and related mental illness.