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淀粉样beta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

岳兴华, 刘晓杰, 武美娜, 陈晋原, 祁金顺

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 太原 030001

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。

关键词： 淀粉样β蛋白; 海马theta节律; 行为脱抑制; 空间学习记忆

分类号：R338.6

[Amyloid β protein suppressed hippocampal theta rhythm and induced behavioral disinhibition and spatial memory deficit in rats.] [Article in Chinese]

YUE Xing-Hua, LIU Xiao-Jie, WU Mei-Na, CHEN Jin-Yuan, QI Jin-Shun

Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education； Functional Center of Medical Experiment, Shanxi Medical University, Taiyuan 030001, China

Abstract

Hippocampal neuronal network oscillation is closely related to the memory, anxiety and behavioral inhibition of mammalian. The cognitive decline and behavioral disinhibition in the patients with Alzheimer's disease (AD) may be relevant to amyloid β protein (Aβ)-induced impairment in hippocampal neuronal cooperative activity. However, it is not well known whether intrahippocampal injection of Aβ could induce behavioral disinhibition and neuronal network disorder, as well as cognition decline in animals. In the present study, we observed the effects of intracerebral injection of Aβ_1-42 on the spatial memory and behavioral inhibition of rats by using Morris water maze and elevated plus-maze tests. Further, we analyzed hippocampal theta rhythm by recording hippocampal local field potential. The results showed that: (1) bilateral hippocampal injection of Aβ_1-42 reduced the anxious behavior of rats, with a significant behavioral disinhibition in the elevated plus-maze test, representing as an increase in the mean entering times and mean residence time in the open arm; (2) Aβ_1-42 injection resulted in a significant impairment of spatial memory in rats, with significantly increased mean escape latencies in hidden platform test; (3) Aβ_1-42 disrupted the induction of theta rhythm induced by tail pinch, with a significant reduction in the peak power, not the peak power frequency of the theta rhythm. These experimental results indicate that intrahippocampal injection of Aβ_1-42 can induce behavioral disinhibition and theta rhythm suppression, as well as spatial memory impairment in rats, which suggests that the cognition deficits and behavior impairments in AD are probably associated with the Aβ-induced disruption of hippocampal theta rhythm and consequent down-regulation of synaptic plasticity.

Key words: amyloid β protein; hippocampal theta rhythm; behavioral disinhibition; spatial learning and memory

收稿日期：2013-09-25　　录用日期：2013-12-13

通讯作者：祁金顺　　E-mail: jinshunqi@sohu.com

引用本文：

岳兴华, 刘晓杰, 武美娜, 陈晋原, 祁金顺. 淀粉样beta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[J]. 生理学报 2014; 66 (2): 97-106.

YUE Xing-Hua, LIU Xiao-Jie, WU Mei-Na, CHEN Jin-Yuan, QI Jin-Shun. [Amyloid β protein suppressed hippocampal theta rhythm and induced behavioral disinhibition and spatial memory deficit in rats.] [Article in Chinese]. Acta Physiol Sin 2014; 66 (2): 97-106 (in Chinese with English abstract).