Aniracetam attenuates H_2O_2-induced deficiency of neuron viability, mi-tochondria potential and hippocampal long-term potentiation of mice in vitro  

阿尼西坦减轻双氧水对小鼠神经元活力、线粒体电位及海马长时程增强的损伤(英文)

作　　者：王永富[1] 李朝翠[1] 蔡景霞[1] 

机构地区：[1]中国科学院昆明动物研究所脑与行为研究室

出　　处：《Neuroscience Bulletin》2006年第5期274-280,共7页神经科学通报（英文版）

摘　　要：Objective It is known that free radicals are involved in neurodegeneration and cognitive dysfunction, as seen in Alzheimer＇s disease （AD） and aging. The present study examines the protective effects of aniracetam against H2O2- induced toxicity to neuron viability, mitochondria potential and hippocampal long-term potentiation （LTP）. Methods Tetrazolium salt 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide （MTT） was used to detect neuronal viability. MitoTracker Red （CMX Ros）, a fluorescent stain for mitochondria, was used to measure mitochondria potential. Electrophysiological technique was carried out to record hippocampual LTE Results H2O2 exposure impaired the viability of neurons, reduced mitochondria potential, and decreased LTP in the CA region of hippocampus. These deficient effects were significantly rescued by pre-treatment with aniracetam （10 ～100μmol/L）. Conclusion These results indicate that aniracetam has a strong neuroprotective effect against H2O2-induced toxicity, which could partly explain the mechanism of its clinical application in neurodegenerative diseases.目的在脑老化和阿尔茨海默尔氏病人脑中,氧自由基的升高是其神经元发生退行性病变,从而导致突触可塑性和认知障碍的机制之一。本文研究了阿尼西坦(aniracetam,一种治疗老年痴呆的药物)对抗双氧水损伤神经元活力,线粒体电位及海马突触传递长时程增强(Long-term potentiation, LTP)的作用。方法用四甲基偶氮唑盐(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide,MTT)法测定神经元的活力,用线粒体荧光探针MitoTracker Red (CMX Ros) 研究线粒体电位的变化,用膜片钳方法记录了海马CA1区的突触传递效能。结果200 μmol/L的双氧水明显损伤小鼠大脑皮层原代培养神经元的细胞活力,降低其线粒体电位,而10 μmol/L或100 μmol/L阿尼西坦预处理能明显对抗双氧水对细胞活力和线粒体电位的降低作用。双氧水在不影响基础突触传递的剂量下(20 μmol/L),却能显著抑制海马LTP的诱导。阿尼西坦在100 μmol/L剂量下,对基础突触传递没有明显影响,对正常小鼠脑片CA1区的LTP也没有易化作用,然而,100 μmol/L的阿尼西坦却能显著地恢复由双氧水损伤的海马LTP。结论本研究结果表明,阿尼西坦对双氧水导致的毒性具有较强的神经保护作用,这为临床上用其治疗神经退行性疾病提供了参考依据。

关 键 词：H2O2 ANIRACETAM neuronal viability mitochondria potential long-term potentiation hippocampus MICE 

分 类 号：R96[医药卫生—药理学]