Kaneko Naoko, Okano Hideyuki, Sawamoto Kazunobu
Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Genes Cells. 2006 Oct;11(10):1145-59. doi: 10.1111/j.1365-2443.2006.01010.x.
Neurogenesis in the subgranular zone of the hippocampal dentate gyrus and olfactory bulbs continues into adulthood and has been implicated in the cognitive function of the adult brain. The basal forebrain cholinergic system has been suggested to play a role in regulating neurogenesis as well as learning and memory in these regions. Herein, we report that highly polysialylated neural cell adhesion molecule (PSA-NCAM)-positive immature cells as well as neuronal nuclei (NeuN)-positive mature neurons in the dentate gyrus and olfactory bulb express multiple acetylcholine receptor subunits and make contact with cholinergic fibers. To examine the function of acetylcholine in neurogenesis, we used donepezil (Aricept), a potent and selective acetylcholinesterase inhibitor that improves cognitive impairment in Alzheimer's disease. Intraperitoneal administrations of donepezil significantly enhanced the survival of newborn neurons, but not proliferation of neural progenitor cells in the subgranular zone or the subventricular zone of normal mice. Moreover, donepezil treatment reversed the chronic stress-induced decrease in neurogenesis. Taken together, these results suggest that activation of the cholinergic system promotes survival of newborn neurons in the adult dentate gyrus and olfactory bulb under both normal and stressed conditions.
海马齿状回颗粒下区和嗅球中的神经发生持续至成年期，并与成年大脑的认知功能有关。有研究表明，基底前脑胆碱能系统在调节这些区域的神经发生以及学习和记忆方面发挥作用。在此，我们报告，齿状回和嗅球中高度多唾液酸化神经细胞黏附分子（PSA-NCAM）阳性的未成熟细胞以及神经元细胞核（NeuN）阳性的成熟神经元表达多种乙酰胆碱受体亚基，并与胆碱能纤维接触。为了研究乙酰胆碱在神经发生中的作用，我们使用了多奈哌齐（安理申），一种强效且选择性的乙酰胆碱酯酶抑制剂，可改善阿尔茨海默病的认知障碍。腹腔注射多奈哌齐可显著提高正常小鼠颗粒下区或脑室下区新生神经元的存活率，但对神经祖细胞的增殖无影响。此外，多奈哌齐治疗可逆转慢性应激诱导的神经发生减少。综上所述，这些结果表明，胆碱能系统的激活在正常和应激条件下均可促进成年齿状回和嗅球中新生神经元的存活。
