How Does Exercise Help Depression? A New Study Adds a Piece to the Puzzle

Exercise is generally accepted as a vital tool in depression treatment.

A recent study in the journal Cell found that exercise also helps protect the brain from harmful substances that contribute to depression.

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We have all heard that we should get more exercise, whether it is to lose weight, lower blood pressure, feel less tired, or improve our mood. Exercise is generally accepted as a vital tool in depression treatment, but we still don’t know why, exactly, exercise improves depression.

There are a variety of possibilities and theories, and we know that physical activity boosts compounds like endorphins that help improve mood. But how else does exercise help depression? A recent study in the journal Cell found that exercise also helps protect the brain from harmful substances that contribute to depression.[1]

The study

Exercise increases the levels of a substance called PGC-1α1 in skeletal muscle. Researchers genetically modified mice to have higher-than-normal levels of PGC-1α1 in their skeletal muscle so that these mice had the characteristic of well-trained, exercised muscles. The modified mice, along with normal control mice, were exposed to stress (through noises, lights, and disrupted schedules) to induce depressive behavior. The researchers fond that after five weeks, the normal mice had developed depressive symptoms as expected, but the mice with increased PGC-1α1 showed no signs of depression.[1]

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Exercise converts a harmful substance formed during stress

Further investigation led the researchers to find that the mice with high PGC-1α1 also had high levels of enzymes called kynurenine aminotransferases (KATs). KATs convert kynurenine into kynurenic acid. During times of stress, kynurenine is produced in the body. Increased levels are associated with mental illness and are known to contribute to depression. Kynurenine likely does this by promoting inflammation, affecting neuronal cell death, and more. In this study, normal mice given kynurenine directly displayed depressive behavior, while those mice with high levels of PGC-1α1 did not.

While kynurenine can travel to the brain, kynurenic acid cannot pass the blood-brain barrier. The KAT enzymes protect the brain by quickly converting kynurenine into kynurenic acid, which cannot reach the brain and cause damage. In the simplest form, the findings show that exercise protects from depression by the following mechanism: exercise increases PGC-1α1, which in turn increases KAT activity, ultimately protecting the brain from the harmful substance kynurenine.

Increase PGC-1α1 by Exercising More

Researchers know that PGC-1α1, which can protect against stress and increase the ability to fight depression, increases with exercise. Maintaining a regular exercise schedule can help you to become more resilient to depressive symptoms, in part due to PGC-1α1 synthesis. Start slowly and try to be consistent; small steps can make a big difference over time.

Share your experience

Does exercise help your depression? What tips do you have for staying active and keeping depression at bay? Share your experience in the comments section below.


[1] Cell. 2014 Sep 25;159(1):33-45.

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