nNOS调控成年海马齿状回神经元再生及其分子机制研究

【作者】 朱新建；

【导师】 朱东亚；

【作者基本信息】 南京医科大学 ， 分子药理学， 2006， 博士

【摘要】 近年来神经科学研究的一项重要进展是发现成年哺乳动物脑内某些特定区域在正常状态下存在着进行性的神经元再生。在某些生理刺激和病理状态下，这些部位的神经发生表现出明显的增强现象。这意味着通过调控某些缺血相关的分子可激活内源性神经元再生机制，促进脑损伤修复。显然，阐明脑缺血激发神经元再生的分子调控机制，将更新中风及其它神经退化性疾病的治疗策略、明晰正确的药物干预环节和发现新药靶。然而，目前关于成年脑神经元再生的研究主要重于发现现象，而决定这些现象的本质问题所知甚少。 NO作为中枢神经系统内的一种新型信号分子在成年脑神经元再生过程中发挥着重要作用，NO以及合成NO的NOS对神经元再生调控的研究目前已成为热点问题。然而目前关于NO／NOS对神经元再生的调控的研究却一直存在着矛盾的结果。新近有报道指出，nNOS源性的NO在生理状态下抑制了成年动物SVZ区的神经元再生。然而，其对海马DG区神经元再生目前为止还存在着争议。此外，我们早期的研究结果表明，局灶性脑缺血后iNOS表达增加激发了海马DG区神经元再生。既然nNOS和iNOS的催化产物都是NO，那么nNOS在脑缺血后的表达有何变化，其对缺血后DG神经元再生有无影响，这些问题目前尚无明确报导，有待进一步确证。更多还原

【Abstract】 Recently, a series of experiments suggested that ongoing neurogenesis in the dentate gyrus not only occurred in the normal adult mammalian brains, but also was enhanced by many physiological activities and pathological events. These findings provide possibility and feasibility for neuronal self-repair after ischemia insult by regulating some ischemia-related molecular. Therefore, discovering the molecular mechanism underlying neurogenesis will help us improve the therapy strategies in stroke and other neurodegeneration diseases and will help us clear the right intervention link of the drug and find new drug target. However, until now, the research about neurogenesis still stayed in the stage of finding phenomena, the mechanism underlies it was little known.As a new signal molecular in the CNS, NO plays an important role in adult neurogenesis in the brain. NO and NOS regulation of neurogenesis has recently became the hot issue. However, the results about the regulation of neurogenesis by NO/NOS are conflicting. Recently two studies show that nNOS-derived NO exerts a negative control on the neurogenesis in the adult SVZ. The two studies however, observed conflicting roles of nNOS-derived NO in the DG neurogenesis.更多还原