Reduced neuronal nitric oxide synthase is involved in ischemia-induced hippocampal neurogenesis by up-regulating inducible nitric oxide synthase expression.

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.

• Authors: Chun Xia Luo, Xin Jian Zhu, Qi Gang Zhou, Bin Wang, Wei Wang, Hui Hui Cai, Yong Jun Sun, Mei Hu, Jun Jiang, Yao Hua, Xiao Han, Dong Ya Zhu
• Journal: Journal of neurochemistry (J Neurochem) Vol. 103 Issue 5 Pg. 1872-82 (Dec 2007) ISSN: 1471-4159 [Electronic] England
• PMID: 17854382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic AMP Response Element-Binding Protein
• Enzyme Inhibitors
• Indazoles
• Nitric Oxide Synthase Type I
• Nitric Oxide Synthase Type II
• 7-nitroindazole

Topics

• Animals
• Brain Infarction (pathology)
• Cell Count (methods)
• Cell Proliferation (drug effects)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Hippocampus (physiopathology)
• Indazoles (pharmacology)
• Infarction, Middle Cerebral Artery (complications)
• Ischemia (etiology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neurons (drug effects, physiology)
• Nitric Oxide Synthase Type I (deficiency, metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Severity of Illness Index
• Up-Regulation (drug effects, genetics, physiology)