淀粉样β蛋白抑制大鼠海马theta节律并致行为脱抑制和空间记忆损伤

发布时间：2018-05-23 18:24

本文选题：淀粉样β蛋白 + 海马theta节律　；参考：《生理学报》2014年02期

【摘要】：海马神经元网络振荡与哺乳动物学习记忆、焦虑及行为抑制密切相关。阿尔茨海默病患者早期表现出的认知功能减退及行为脱抑制,极可能与海马内沉积的淀粉样β蛋白(amyloid β protein,Aβ)损伤了海马神经元网络电活动有关,但海马注射Aβ能否在伤害学习记忆功能的同时也引起行为脱抑制和改变神经元同步化活动,仍缺乏足够的动物实验证据。本研究利用Morris水迷宫、高架十字迷宫和在体局部场电位记录技术,观察了海马注射Aβ1 42寡聚体对大鼠空间学习记忆和行为抑制活动的影响,并分析了海马theta节律的改变。结果表明,与对照组相比,海马注射Aβ1 42寡聚体两周后:(1)大鼠在高架十字迷宫中焦虑性减低,出现明显的行为脱抑制现象,去开臂次数和在开臂停留时间均明显增加;(2)大鼠空间学习、记忆严重受损,水迷宫定位航行实验中寻找水下平台的潜伏期明显延长,空间探索实验中在原平台象限的游泳时间百分比明显减小;(3)大鼠海马CA1区theta节律压抑,由夹尾刺激诱导的theta节律的功率峰值明显减低,而theta节律功率峰值对应的频率值未发生改变。以上结果表明,海马注射Aβ1 42寡聚体可同时引起大鼠行为脱抑制、空间记忆损伤和海马theta节律压抑。这提示,AD患者出现的学习记忆能力障碍和精神行为异常很可能与Aβ对海马神经元网络theta节律活动的压抑以及由此引起的突触可塑性下调有关。
[Abstract]:Hippocampal neuronal network oscillation is closely related to mammalian learning and memory, anxiety and behavioral inhibition. Early cognitive impairment and behavioral deinhibition in patients with Alzheimer's disease may be related to amyloid 尾 protein A 尾 (amyloid 尾 protein A 尾), which impairs the electrical activity of hippocampal neurons. However, there is still insufficient evidence of whether hippocampal injection of A 尾 can injure learning and memory function, but also induce behavioral deinhibition and change neuronal synchronization. In this study, Morris water maze, elevated cross maze and in vivo local field potential recording techniques were used to observe the effects of A 尾 1 Oligomer on spatial learning, memory and behavioral inhibition in rats, and to analyze the changes of theta rhythm in hippocampus. The results showed that compared with the control group, the anxiety in the elevated cross labyrinth was decreased in rats injected with A 尾 1 42 oligomer in hippocampus two weeks later. The number of arm removal and the time of staying in the open arm increased significantly (P < 0.05). The spatial learning and memory of rats were severely damaged, and the latency of finding underwater platform in the water maze navigation experiment was prolonged obviously. In the space exploration experiment, the percentage of swimming time in the original platform quadrant was significantly reduced. (3) the theta rhythm in the CA1 region of the hippocampus was suppressed, and the peak power of the theta rhythm induced by the clip tail stimulation was significantly decreased. However, the frequency corresponding to the peak of theta rhythmic power did not change. These results suggest that the injection of A 尾 1 / 42 oligomer into the hippocampus can simultaneously induce behavioral deinhibition, spatial memory impairment and inhibition of theta rhythm in the hippocampus of rats. These results suggest that the disorder of learning and memory and the abnormal mental behavior in AD patients may be related to the inhibition of theta rhythm of hippocampal neuron network by A 尾 and the downregulation of synaptic plasticity caused by A 尾.
【作者单位】：山西医科大学生理学系细胞生理学省部共建教育部重点实验室;山西医科大学基础医学院机能实验中心;
【基金】：supported by the National Natural Science Foundation of China(No.31271201) the Special Foundation for the Doctoral Program of Higher Education of Ministry of Education,China(No.20101417110001) the Natural Science Foundation of Shanxi Province,China(No.2010011049-3,2010-51)
【分类号】：R749.16

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