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目的:探讨选择性激动α7-N型乙酰胆碱受体(α7nAChR)对痴呆小鼠空间参考记忆和被动回避记忆功能的影响。方法:小鼠45只随机分为3组:对照组、模型组、干预组。对照组侧脑室内注射生理盐水, 模型组侧脑室内注射Aβ25-35, 干预组连续14天腹腔注射α7nAChR激动剂DMXB, 采用Morris水迷宫和Y型电迷宫观察3组小鼠的行为学表现, 电生理检测脑片海马CA1区突触长时程增强(LTP)以观察小鼠的学习记忆功能。结果:水迷宫训练第5天, 模型组小鼠与对照组相比逃逸潜伏期增加, 目标象限探索距离百分比、目标象限探索时间百分比、穿越原平台位置次数显著减少, 干预组与对照组小鼠之间各项指标无显著性差异。与对照组相比, 模型组小鼠在Y型电迷宫训练第5天的错误反应次数和全天总反应时间明显增加, 干预组与模型组小鼠之间无显著性差异。侧脑室内注射Aβ25－35损害海马LTP诱导, DMXB的干预可恢复LTP。结论:Aβ25-35介导的神经毒性作用诱导AD小鼠, 空间参考记忆和被动回避记忆明显减退, 选择性激动α7nAChR可以改善小鼠空间参考记忆, 对被动回避记忆没有影响。
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Objective: To explore effects of selective activation of alpha7 nicotinic acetylcholine receptor (α7nAChR) on spatial reference memory and avoidance learning memory in Amyloid β-peptide(Aβ25-35) induced Alzheimer Disease(AD) mice. Methods: Forty-five mice were randomly divided into 3 groups: control group, model group and. The control group received the intracerebroventricular(ICV) saline injection, the dementia mice model group received, and the DMXB group received the ICV injection of Aβ25-35 and followed the ICV injection of α7nAChR agonist. Using Morris water maze and Y type maze, the mice behavior was measured, electrical synapses physiological testing in mice brain slices hippocampal CA1 was used to measure the synaptic long-term potentiation(LTP) related to learning and memory functions. Results: On the day 5 of Morris water maze test, escape latency of the model group was significantly higher than the control group, whereas the percentage of distance exploration target quadrant, the percentage of time exploring the target quadrant, and the times of crossing the situation of platform were significantly lower than the control group. There was no significant difference between the DMXB group and the control group. On the day 5 of Y-maze test, the model group showed higher error numbers (EN) and total reaction time(TRT) than control group. There was no significant difference between the DMXB group and the model group. ICV injection Aβ25-35 damaged hippocampus LTP induction, and DMXB intervention could facilitate LTP. Conclusion: These findings suggested that the Aβ25-35-induced neurodegeneration in AD model by α7nAChR mediated neurotoxicity. Selective activation of α7nAChR can improve spatial reference memory in mice, had no effect on avoidance learning memory.
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