Protection from stress-induced depression

Depression, which currently affects more than 350 million people worldwide, can manifest itself in a number of ways and, increasingly, those with depression can seek a number of coping strategies such as cognitive brain therapies, medications and almost all forms of exercise - though none are considered mutually exclusive.

But until now, it has been unclear exactly why physical exercise is particularly beneficial to those who suffer from cases of stress-induced depression.

“In neurobiological terms, we actually still don’t know what depression is

Study co-author Mia Lindskog

In research published in the journal Cell, a group of scientists from the Karolinska Institutet, Sweden has revealed 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.

Prior to the study, it was known that the protein PGC-1?1 increases in skeletal muscle with exercise, and mediates the beneficial muscle conditioning in connection with physical activity.

For the purposes of its study, the research team used a genetically modified mouse with high levels of PGC-1?1 in skeletal muscle that shows many characteristics of well-trained muscles.

The genetically modified mouse, alongside a group of control mice, was 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 behaviour, whereas the genetically modified mouse - with well-trained muscle characteristics - had no depressive symptoms.

“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,” said Mia Lindskog, researcher at the Department of Neuroscience at Karolinska Institutet.

Jorge Ruas, principal investigator at the Department of Physiology and Pharmacology, Karolinska Institutet, said: “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.”

According to researchers, mice with higher levels of PGC-1?1 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.

Though the exact function of kyurenine remains unknown, high levels of the substance has also be measured in patients that suffer from mental illness.

Researchers said that developing a new strain of drugs based on their study could become an additional way to treat stress-induced depression.

“These antidepressants would not need to cross the blood-brain barrier to act on the brain (since their mechanism of action would be activating muscle as a kynurenine detoxification organ). For that reason, one can imagine that such antidepressants could have less secondary effects,” Ruas told LaboratoryTalk.

Ruas said that his research team is planning to evaluate this mechanism in patients suffering from depression, to whom physical exercise is prescribed as an antidepressant co-therapy.

“Of course all of this needs to be tested and investigated,” he said.

During August, depression was brought directly under the spotlight after the US actor and comedian Robin Williams was found dead at his home in California.

Immediately after his death was announced, Williams’ publicist confirmed he had been battling severe depression and a coroner’s report confirmed he took his own life.