Reduced neuronal nitric oxide synthase is involved in ischemia-induced hippocampal neurogenesis by up-regulating inducible nitric oxide synthase expression |
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Authors: | Luo Chun Xia Zhu Xin Jian Zhou Qi Gang Wang Bin Wang Wei Cai Hui Hui Sun Yong Jun Hu Mei Jiang Jun Hua Yao Han Xiao Zhu Dong Ya |
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Affiliation: | Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China; Laboratory of Mammalian Genes, Nanjing Medical University, Nanjing, China |
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Abstract: | Nitric oxide (NO), a free radical with signaling functions in the CNS, is implicated in some developmental processes, including neuronal survival, precursor proliferation, and differentiation. However, neuronal nitric oxide synthase (nNOS) -derived NO and inducible nitric oxide synthase (iNOS) -derived NO play opposite role in regulating neurogenesis in the dentate gyrus after cerebral ischemia. In this study, we show that focal cerebral ischemia reduced nNOS expression and enzymatic activity in the hippocampus. Ischemia-induced cell proliferation in the dentate gyrus was augmented in the null mutant mice lacking nNOS gene (nNOS−/−) and in the rats receiving 7-nitroindazole, a selective nNOS inhibitor, after stroke. Inhibition of nNOS ameliorated ischemic injury, up-regulated iNOS expression, and enzymatic activity in the ischemic hippocampus. Inhibition of nNOS increased and iNOS inhibitor decreased cAMP response element-binding protein phosphorylation in the ipsilateral hippocampus in the late stage of stroke. Moreover, the effects of 7-nitroindazole on neurogenesis after ischemia disappeared in the null mutant mice lacking iNOS gene (iNOS−/−). These results suggest that reduced nNOS is involved in ischemia-induced hippocampal neurogenesis by up-regulating iNOS expression and cAMP response element-binding protein phosphorylation. |
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Keywords: | cerebral ischemia cyclic AMP response element-binding protein hippocampus inducible nitric oxide synthase neurogenesis neuronal nitric oxide synthase |
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