VGF gene is upregulated by exercise in mice and functions like a powerful antidepressant, according to Nature Medicine paper.

Boosting an exercise-related gene in the brain works as a powerful antidepressant in mice, according to investigators at Yale School of Medicine.

The Yale team designed a custom microarray that was optimized to show small changes in gene expression, particularly in the brain’s hippocampus, which is highly sensitive to stress hormones, depression, and antidepressants. Then they compared the brain activity of sedentary mice to those who were given running wheels.

The researchers observed that the mice with wheels were, within one week, running more than six miles each night. Four independent array analyses of the mice turned up 33 hippocampal exercise-regulated genes—27 of which had never been identified before, report the scientists.

The action of one gene in particular, VGF, was greatly enhanced by exercise. Moreover, administering VGF functioned like a powerful antidepressant, while blocking VGF inhibited the effects of exercise and induced depressive-like behavior in the mice.

“Identification of VGF provides a mechanism by which exercise produces antidepressant effects,” says Ronald Duman, professor of psychiatry and senior author of the study. “This information further supports the benefits of exercise and provides a novel target for the development of new antidepressants with a completely different mechanism of action than existing medications.”

The report was published December 2 in Nature Medicine.

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