A new study, published in the journal Cell, investigates the mechanisms behind the protection from stress-induced depression offered by physical exercise.
Depression is a debilitating mental illness affecting an estimated 1 in 10 adults in the U.S. each year. Despite significant advances in the diagnosis and treatment of depression, the condition remains the leading cause of disability worldwide.
Currently, anti-depressants and psychotherapy are considered to be the most effective treatments for the disorder. However, exercise also has well-known benefits against symptoms of depression.
In fact, a systematic review of 35 randomized controlled trials published last year found that exercising was as beneficial for people with depression as therapy or antidepressants. However, the researchers cautioned that higher quality studies are needed to confirm the results.
Scientists know that during exercise, there is an increase in skeletal muscle of a protein called PGC-1a1. The researchers behind the new study – from the Karolinska Institute in Sweden – wanted to see whether this protein increase might be implicated in the protective benefits of exercise.
In the study, genetically modified mice with high levels of PGC-1a1 in skeletal muscle (that showed many characteristics of well-trained muscles) were exposed – along with normal mice – to a stressful environment in the lab. This involved being exposed to loud noises, flashing nights and having their circadian rhythm reversed at irregular intervals.
After 5 weeks of being exposed to mild stress, the normal mice developed symptoms of depression, whereas the genetically modified mice displayed no depressive behavior.
“Our initial research hypothesis was that trained muscle would produce a substance with beneficial effects on the brain,” says Dr. Jorge Ruas, principal investigator at the Department of Physiology and Pharmacology, Karolinska Institute. “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.”
Investigating the genetically modified mice further, the researchers made the discovery that, in addition to the elevated levels of PGC-1a1, the mice also had higher levels of KAT enzymes. These enzymes convert kynurenine – a substance formed during stress – into kynurenic acid. The exact function of this acid is not known, but patients with mental illness are known to have high levels of it.
Kynurenine conversion process ‘may be protective mechanism’
When normal mice were given kynurenine as part of the study, the researchers found that they exhibited symptoms of depression. However, when the elevated PGC-1a1 mice were given kynurenine, their behavior seemed unaffected.
The researchers also noticed that even when the PGC-1a1 mice were administered kynurenine, their blood did not show raised levels of kynurenine. This is because the KAT enzymes in the trained muscles of the PGC-1a1 mice were able to quickly convert it to kynurenic acid. The researchers think that this quick conversion process therefore, is a protective mechanism.
“In neurobiological terms, we actually still don’t know what depression is,” says Dr. Mia Lindskog, researcher at the Department of Neuroscience at Karolinska Institute. “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.”
“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,” adds Dr. Ruas. “Skeletal muscle appears to have a detoxification effect that, when activated, can protect the brain from insults and related mental illness.”
The team acknowledges that other factors influence a person’s likelihood of experiencing depression, including their genetic makeup. But, they add, the research demonstrates that regardless of individual predispositions, there’s a clear take-away for everyone: “It’s definitely worth taking note that if you’re currently active, you should sustain it. If you’re not physically active, you should initiate the habit.”
“The impact of being active goes far beyond the physical,” they conclude.