“If you consistently exercise and your muscle is conditioned and adapted to physical exercise, then you acquire the ability to express this class of enzymes that have the ability to detoxify something that accumulates during stress and that will be harmful for you,” senior study author Dr. Jorge Ruas of the Karolinska Institutet in Stockholm said in a telephone interview with Reuters Health.
The body metabolizes this substance, kynurenine, from tryptophan, a process that is activated by stress and by inflammatory factors, Dr. Ruas and his team explain in their report, published in Cell. Studies have linked high levels of kynurenine - which readily crosses the blood-brain barrier - to depression, suicide and schizophrenia.
Their new study was done in skeletal muscle-PGC-1alpha1 transgenic mice, which were genetically modified to express high levels of this protein in their muscles, mimicking the effects of aerobic muscle conditioning. The researchers subjected these mice, as well as a control group of wild-type mice, to five weeks of mild stress. The normal mice developed signs of depression, but the PGC-1alpha1 mice didn’t.
In addition to higher levels of kynurenine in their blood, the transgenic mice also had higher levels of KAT enzymes, which convert kynurenine into kynurenic acid, a more easily mebabolized form that can’t cross the blood-brain barrier.
When the researchers directly administered kynurenine to the PGC-1alpha1 mice, their blood levels of the substance did not increase, because the KAT enzymes were able to break it down so quickly. However, giving kynurenine to the wild-type mice increased their blood levels of the chemical, and also caused depressive symptoms.
To ensure that the findings in mice would apply to people, the researchers recruited a group of adult volunteers to participate in three weeks of moderate exercise. At the end of the exercise program, the volunteers had more PGC-1alpha1 and KAT enzymes in their muscle.
Dr. Ruas and his colleagues are now planning a study in people with depression who have been prescribed physical exercise as therapy. The study would investigate how much patients actually exercised, whether the physical activity was helpful in treating their depression, and also the correlation among exercise, depression and kynurenine levels.
Clinicians can use the findings to help their patients understand why physical activity can fight off depression, Dr. Ruas said, which may improve their compliance with exercise recommendations.