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.
Sheng Li Xue Bao. 2014 Apr 25;66(2):97-106.
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.
海马体神经网络振荡与哺乳动物的记忆、焦虑和行为抑制密切相关。阿尔茨海默病(AD)患者的认知衰退和行为脱抑制可能与淀粉样β蛋白(Aβ)诱导的海马体神经元合作活动受损有关。然而,海马体内注射Aβ是否会导致动物行为脱抑制、神经网络紊乱以及认知衰退尚不清楚。在本研究中,我们通过Morris水迷宫和高架十字迷宫试验观察了脑内注射Aβ(1-42)对大鼠空间记忆和行为抑制的影响。此外,我们通过记录海马体局部场电位来分析海马体θ节律。结果表明:(1)双侧海马体注射Aβ(1-42)可降低大鼠的焦虑行为,在高架十字迷宫试验中出现明显的行为脱抑制,表现为在开放臂的平均进入次数和平均停留时间增加;(2)注射Aβ(1-42)导致大鼠空间记忆显著受损,在隐藏平台试验中平均逃避潜伏期显著增加;(3)Aβ(1-42)破坏了夹尾诱导的θ节律的诱导,θ节律的峰值功率显著降低,而不是峰值功率频率。这些实验结果表明,海马体内注射Aβ(1-42)可诱导大鼠行为脱抑制、θ节律抑制以及空间记忆损伤,这表明AD中的认知缺陷和行为损伤可能与Aβ诱导的海马体θ节律破坏以及随之而来的突触可塑性下调有关。