Physical exercise has many beneficial effects on human health, including the protection from stress-induced depression. However, until now the mechanisms that mediate this protective effect have been unknown. A 2014 study demonstrates 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. 

The study provides an explanation for the protective biochemical changes induced by physical exercise that prevent the brain from being damaged during stress.

Dr Jorge Ruas explains:

"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." 

"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. Skeletal muscle appears to have a detoxification effect that, when activated, can protect the brain from insults and related mental illness."

Reference:

Leandro Z. Agudelo, Teresa Femenía, Funda Orhan, Margareta Porsmyr-Palmertz, Michel Goiny, Vicente Martinez-Redondo, Jorge C. Correia, Manizheh Izadi, Maria Bhat, Ina Schuppe-Koistinen, Amanda Pettersson, Duarte M. S. Ferreira, Anna Krook, Romain Barres, Juleen R. Zierath, Sophie Erhardt, Maria Lindskog, and Jorge L. Ruas. Skeletal Muscle PGC-1a1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression. Cell, September 2014