Besides the short-term feel-good endorphins released during exercise, scientists have known that physically fit people are also better protected from stress-induced depression. But the reason for this benefit wasn’t clear until a new study by researchers at Sweden’s Karlinska Institutet unlocked how the brain is protected by exercise.
Research has shown that workout out raises the level of a protein called PGC-1a1 in skeletal muscle. The Swedish team honed in on this protein, genetically modifying mice to produce more of the protein, which led to their skeletal muscles showing characteristics of training even without exercise, they report in the journal Cell.
These mice, as well as a group of non-modified control mice, were kept under stressful conditions that included loud noises, flashing lights and disruption of their natural circadian rhythms. After five weeks, the normal mice had become depressed, but the genetically modified mice showed no symptoms or behaviors of depression.
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The researchers’ initial hypothesis was that the PGC-1a1 enhanced muscles would produce a brain-boosting substance, but that’s not what happened.
"We actually found the opposite: Well-trained muscle produces an enzyme that purges the body of harmful substances,” Jorge Ruas, principal investigator at the Department of Physiology and Pharmacology, Karolinska Institutet said in a statement. “So in this context the muscle's function is reminiscent of that of the kidney or the liver."
The enhanced mice also showed higher levels of an enzyme called KAT, which converts a metabolism byproduct, kynurenine, that forms during stress into kynurenic acid, which cannot pass the blood-brain barrier. Though the exact function of kynurenine isn’t known, it’s present in high levels in mentally ill patients.
In fact, mice in the PGC-1a1 were not only unaffected by their stressful environment, their kynurenine levels never rose since it was so rapidly converted by their muscles.
"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,” Ruas said. “Skeletal muscle appears to have a detoxification effect that, when activated, can protect the brain from insults and related mental illness.”
The puzzle of depression
Depression is estimated to affect 350 million people worldwide, and scientists are still unsure of its cause and chemistry. "In neurobiological terms, we actually still don't know what depression is,” said Mia Lindskog, a researcher at the Department of Neuroscience at Karolinska Institutet. “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."