Exercise-Induced Nitric Oxide Contributes to Spatial Memory and Hippocampal Capillaries in Rats.

Exercise has been argued to improve cognitive function in both humans and rodents. Angiogenesis significantly contributes to brain health, including cognition. The hippocampus is a crucial brain region for cognitive function. However, studies quantifying the capillary changes in the hippocampus after running exercise are lacking. Moreover, the molecular details underlying the effects of running exercise remain poorly understood. We show that endogenous nitric oxide contributes to the beneficial effects of running exercise on cognition and hippocampal capillaries. Four weeks of running exercise significantly improved spatial memory ability and increased the number of capillaries in the cornu ammonis 1 subfield and dentate gyrus of Sprague-Dawley rats. Running exercise also significantly increased nitric oxide synthase activity and nitric oxide content in the rat hippocampus. After blocking the synthesis of endogenous nitric oxide by lateral ventricular injection of NG-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, the protective effect of running exercise on spatial memory was eliminated. The protective effect of running exercise on angiogenesis in the cornu ammonis 1 subfield and dentate gyrus of rats was also absent after nitric oxide synthase inhibition. Therefore, during running excise, endogenous nitric oxide may contribute to regulating spatial memory ability and angiogenesis in cornu ammonis 1 subfield and dentate gyrus of the hippocampus.