Marin P, Maus M, Desagher S, Glowinski J, Prémont J
Laboratoire de Neuropharmacologie, INSERM U114, Collège de France, Paris.
Neuroreport. 1994 Oct 3;5(15):1977-80. doi: 10.1097/00001756-199410000-00035.
The role of cholinergic mechanisms in N-methyl-D-aspartate (NMDA)-mediated neuronal death was investigated using mouse striatal neurones in primary culture. A 30 min exposure of striatal neurones to increasing concentrations of NMDA resulted 24 h later in dramatic neuronal degeneration as assessed by MTT staining, crystal violet incorporation and determination of microtubule-associated protein 2. The NMDA-induced neurodegeneration was strongly inhibited by the co-application of two non-selective cholinergic agonists, acetylcholine or carbachol. This protective effect appears to be mediated by nicotinic receptors since it was insensitive to the muscarinic antagonist atropine but mimicked by nicotine, nornicotine and 1,1-dimethyl-4-phenyl-piperazinium. Moreover, the nicotine-evoked neuroprotection was inhibited by the central nicotinic antagonist hexamethonium. Therefore, this study suggests that cholinergic interneurones play an important role in neuronal survival in the striatum.
利用原代培养的小鼠纹状体神经元，研究了胆碱能机制在N-甲基-D-天冬氨酸（NMDA）介导的神经元死亡中的作用。纹状体神经元暴露于浓度不断增加的NMDA 30分钟后，24小时后通过MTT染色、结晶紫掺入和微管相关蛋白2的测定评估，出现了显著的神经元变性。两种非选择性胆碱能激动剂乙酰胆碱或卡巴胆碱共同应用可强烈抑制NMDA诱导的神经变性。这种保护作用似乎是由烟碱受体介导的，因为它对毒蕈碱拮抗剂阿托品不敏感，但可被尼古丁、去甲烟碱和1,1-二甲基-4-苯基哌嗪模拟。此外，尼古丁诱发的神经保护作用被中枢烟碱拮抗剂六甲铵抑制。因此，本研究表明胆碱能中间神经元在纹状体神经元存活中起重要作用。
