We found that the expression and activity of endothelial nitric oxide synthase (eNOS) is increased in the hippocampus during exercise (Moon et al., 2006). However, the upstream regulatory factor on the eNOS expression in the hippocampus during exercise has not been clear. In this study, we investigate the role of acetylcholine (ACh) as a regulatory factor for the eNOS expression and activity in the hippocampus during exercise. The results of the present study demonstrate that voluntary wheel running exercise for two weeks increases the expression and activity eNOS. In addition, choline acetyltransferase (ChAT) immnunoreacitvity within the hippocampus was increased after 2 weeks exercise. We further found that the upregulation of ACh with treatment of physostigmine, a booster of ACh releasing, increase the expression and activity of eNOS in the hippocampus. This present study provides the evidence that the upregulation of eNOS during exercise may be mediated by ACh in the hippocampus.
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