Exercise and the Brain

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Exercise and the Brain

In animals, exercise seems to enhance neuronal resilience.

Exercise feels good, but does it benefit the brain physiologically? In this study series, researchers examined neuroprotective genes in the hippocampus in sedentary mice and in mice placed in cages with running wheels.

By 1 week, exercising mice ran 10 km per night (probably the equivalent of nightly human marathons); exercise induced 33 hippocampal genes. Some genes (e.g., for the brain-derived neurotropic factor [BDNF] receptor) were involved in the mitogen-activated protein kinase (MAPK) signaling pathway. By stimulating the MAPK pathway through exercise, researchers induced genes for VGF, a neuropeptide precursor involved in energy balance, and neuritin, a neuroplasticity gene. Compared with sedentary mice, exercising mice had increases of both BDNF and VGF protein in the hippocampus.

Mice administered synthetic VGF had reduced immobility in the forced-swim and tail-suspension tests, which are considered animal analogues for depression, but had no changes in mouse models of anxiety. Compared with wild-type mice, both sedentary and exercising mice mutants with one null Vgf gene had lower hippocampal VGF and greater immobility in the depression analogue tests. VGF increased with exercise in mutant mice, but not to the extent seen in wild-type exercising mice. Cell-culture studies showed that VGF induced several neuroplasticity genes.

Comment: VGF may be a common pathway by which exercise induces neuroplasticity and growth-factor genes; at least one of these might act similarly to antidepressants in promoting an adaptive response to stress. However, the tests used here may be modeling stress-induced helplessness, not depression. It would be premature to conclude that antidepressants target one or more of the induced genes and that VGF is a novel antidepressant. Still, exercise seems to induce multiple interacting genes that enhance neuronal resilience. More people should exercise regularly, even if they cannot attain the mouse standard of running 10 km per day.

— Steven Dubovsky, MD

Published in Journal Watch Psychiatry February 25, 2008