Ho New Fei, Han Siew Ping, Dawe Gavin S
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Life Sciences (CeLS), Level 4, 28 Medical Drive, 117456, Singapore.
BMC Neurosci. 2009 Jun 5;10:57. doi: 10.1186/1471-2202-10-57.
Cholinergic neuronal dysfunction of the basal forebrain is observed in patients with Alzheimer's disease and dementia, and has been linked to decreased neurogenesis in the hippocampus, a region involved in learning and memory. Running is a robust inducer of adult hippocampal neurogenesis. This study aims to address the effect of running on hippocampal neurogenesis in lesioned mice, where septohippocampal cholinergic neurones have been selectively eliminated in the medial septum and diagonal band of Broca of the basal forebrain by infusion of mu-p75-saporin immunotoxin.
Running increased the number of newborn cells in the dentate gyrus of the hippocampus in cholinergic denervated mice compared to non-lesioned mice 24 hours after injection of bromodeoxyuridine (BrdU). Although similar levels of surviving cells were present in cholinergic depleted animals and their respective controls four weeks after injection of BrdU, the majority of progenitors that proliferate in response to the initial period of running were not able to survive beyond one month without cholinergic input. Despite this, the running-induced increase in the number of surviving neurones was not affected by cholinergic depletion.
The lesion paradigm used here models aspects of the cholinergic deficits associated with Alzheimer's Disease and aging. We showed that running still increased the number of newborn cells in the adult hippocampal dentate gyrus in this model of neurodegenerative disease.
在阿尔茨海默病和痴呆患者中观察到基底前脑胆碱能神经元功能障碍，且这与海马体神经发生减少有关，海马体是一个参与学习和记忆的区域。跑步是成年海马体神经发生的有力诱导因素。本研究旨在探讨跑步对损伤小鼠海马体神经发生的影响，在这些小鼠中，通过注入μ-p75-皂草素免疫毒素，基底前脑内侧隔区和布罗卡斜带中的隔海马胆碱能神经元已被选择性消除。
与未损伤小鼠相比，在注射溴脱氧尿苷（BrdU）24小时后，跑步增加了胆碱能去神经支配小鼠海马齿状回中新生细胞的数量。虽然在注射BrdU四周后，胆碱能缺失动物及其各自对照组中存活细胞的水平相似，但在没有胆碱能输入的情况下，大多数在跑步初期增殖的祖细胞无法存活超过一个月。尽管如此，跑步诱导的存活神经元数量增加不受胆碱能缺失的影响。
此处使用的损伤模型模拟了与阿尔茨海默病和衰老相关的胆碱能缺陷的各个方面。我们表明，在这个神经退行性疾病模型中，跑步仍然增加了成年海马齿状回中新生细胞的数量。
