Depressed? Get off the couch.

By Amy Norton

Exercise seems to increase the production of naturally occurring brain chemical with antidepressant effects in mice, researchers reported Sunday.

The findings, published in the journal Nature Medicine, point to potential new ways to treat depression in people.

Studies have found that exercise can help ease depression symptoms, but the reasons for the benefit have not been clear. For the new study, scientists used a tool called a microarray to examine how exercise changed gene activity in the brains of mice.

They focused on a brain region known as the hippocampus, which has been implicated in mood regulation and in the brain's response to antidepressant medication.

The researchers found that mice that had a week's worth of workouts on a running wheel showed altered activity in a total of 33 genes, the majority of which had never been identified before.

In particular, exercise enhanced activity in the gene for a nerve growth factor known as VGF. Nerve growth factors are small proteins important in the development and maintenance of nerve cells.

Moreover, when the researchers infused a synthetic version of VGF into the brains of the mice, it produced a "robust antidepressant effect" in standardized tests of animals placed in stressful situations.

"The major finding is that we have identified a key factor that underlies the antidepressant effects of exercise -- information that could be used for the development of novel therapeutic agents," said senior researcher Dr. Ronald S. Duman of Yale University in New Haven, Connecticut.

Exercise "clearly has effects on the brain," he told Reuters Health, and they are both direct and indirect. It's possible, he explained, that the current findings reflect a direct effect of exercise on nerve cells in the hippocampus, or more general changes in the brain, like better blood flow or increased hormonal activity.

Besides offering more support for the benefits of exercise, the findings also point to VGF as a target for new antidepressants, according to Duman and his colleagues. Such medications, they point out, would work by an entirely different mechanism than existing antidepressants, which are effective for about 65 percent of patients.