Building strong muscles seems to protect the brain from stress-induced depression. (Shannon Stapleton/Reuters)

First came end orphins, those home-grown opioids or painkillers that produce a “runner’s high.” Then came the endocannabinoids, the pleasure-inducing molecules released during hard workouts that turn exercise nuts into gym rats. Now, decades after scientists first speculated on the effects of physical activity on the brain, Swedish researchers have discovered a new reason for lacing up those sneakers:

Exercise not only feels good, it may also protect the brain from depression.

In mouse studies at the Karolinska Institute in Stockholm, neuroscientists showed that exercise helped rid the body of kynurenine, a stress-induced amino acid associated with mental illness.

“Our initial research hypothesis was that trained muscle would produce a substance with beneficial effects on the brain,” Jorge Ruas, principal investigator at Karolinska’s Department of Physiology and Pharmacology, said last week. “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 liver.”

Well-trained muscles produce increased levels of a protein known as PGC-1(alpha)1. The Swedish scientists developed a genetically modified mouse strain with high levels of the protein in their muscles and exposed those mice (as well as normal mice) to a highly stressful environment of noises and flashing lights. After five weeks, the normal mice showed evidence of depressed behavior, including lethargy and indifference to food, but the genetically modified mice did not.

The reason, the scientists believe, is that the modified mice had above-normal levels of KAT, an enzyme that, under stress, converts kynurenine into kynurenic acid, which cannot cross the blood-brain barrier. In effect, KAT in these muscled-up mice detoxed their brains of stress-related neurochemicals.

“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 [when activated] can protect the brain from insults and related mental illness.”