Exercise and the prevention of depression

Need another reason to hit the gym?  A new piece of research from Sweden found that the mood-boosting effect of physical exercise isn’t just about improved body image and higher energy levels—during exercise, the muscle seems to actually purge the blood of a substance thought to be harmful to the brain.  “In this context, the muscle’s function is reminiscent of that of the kidney or the liver,” said Jorge Ruas, principal investigator for the study.

Researchers bred genetically modified mice to have very high levels of the protein PGC-1a1, a protein which is found in the muscles of all mice (and humans) after the muscle becomes conditioned by exercise.  Genetically modified mice and normal mice were exposed to a mild stressors in their environment (loud noise, flashing lights, and a reversal of sleep-wake cycles at unpredictable periods) for five weeks.  The normal mice developed signs of depressive behaviour after five weeks, but the genetically modified mice did not.

But why?  Researchers found that the mice with higher levels of PGC-1a1 in their muscle also had increased levels of the enzyme KAT, an enzyme which converts a substance called kynurenine into an acid that can’t pass from the blood to the brain.  Scientists don’t know exactly what kynurenine does, but we know that higher levels of it can be measured in patients with mental illness.  This fact was also demonstrated in the study—normal mice directly exposed to kynurenine showed depressive behaviour, but the genetically modified mice did not.  In fact, elevated kynerenine levels never even appeared in their brains since the enzyme KAT was so good at clearing it from their blood.

In short: it looks like exercise causes high levels of a substance in the muscle which can effectively detoxify depression-causing substances in the blood.  “It is 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 seems to have a dexotification effect that, when activated, can protect the brain from insults and related mental illness,” says Ruas. 

In the meantime, going for a morning spin class or an after-work jog might be just the thing to clear the mind—quite literally. 


Story Source:
The above article is based on materials provided by Karolinska Institutet.

Journal 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