Physical Exercise Prevents Stress-Induced Activation of Granule Neurons and Enhances Local Inhibitory Mechanisms in the Dentate Gyrus

J Neurosci. 2013 May 1;33(18):7770-7. Schoenfeld TJ, Rada P, Pieruzzini PR, Hsueh B, Gould E. “Physical exercise is known to reduce anxiety”. The ventral hippocampus is an important region that is involved in the regulation of stress and anxiety. In this study, the authors investigated the effects of exercise (running) on the ventral hippocampus after subjecting the animals to anxiety provoking stimulus. The authors tested the expression of c-fos and arc as an indirect measure to evaluate neuronal activation after performing cold water swim stress in sedentary and running mice. Stress increased the expression of the proteins tested under sedentary condition but not under active condition. In order to test whether running modifies the inhibitory activation to a stressor, the authors measured the expression of c-fos and arc by inhibitory interneurons, amount of GABA release and expression of vesicular GABA transporter (vGAT) in the hippocampus. Running increased the local inhibitory mechanisms in the hippocampus, showed by enhanced expression of vGAT and extracellular GABA release during cold water swim stress. Further blocking of GABAA receptors with bicuculline in the ventral hippocampus reversed the anxiolytic effect of running. These findings suggest that the running plays an important role in improving the regulation of anxiety through inhibitory mechanisms in the ventral hippocampus. - Madhan