快速老化小鼠P8海马神经元突触可塑性相关的AMPA受体表达异常

Abnormal expression of AMPA receptor in hippocampus of senescence accelerated mouse prone 8 correlated to synaptic plasticity

目的比较快速老化小鼠P8(SAMP8)与抗快速老化小鼠R1(SAMR1)海马神经元突触可塑性相关的谷氨酸α-氨基-3-羟基-5-甲基-4-异唑丙酸(AMPA)受体表达差异,为阿尔兹海默病(AD)的发病机制提供实验依据。方法取雄性10月龄SAMP8 10只和SAMR1 9只,应用Morris水迷宫实验评价动物学习记忆能力,透射电子显微镜观察海马CA1区神经元突触界面超微结构,蛋白质免疫印迹法检测海马AMPA受体亚基GluR1、GluR2的表达。结果与SAMR1比较,SAMP8逃避潜伏期延长,目标象限时间百分比下降,穿台次数减少;海马CA1区神经元突触后致密带变薄,突触间隙增宽,突触界面曲率下降;海马GluR2含量下降,GluR1含量有下降趋势,但差异无统计学意义。结论海马AMPA受体异常可能是导致突触可塑性受损,引发SAMP8认知障碍的原因之一,AMPA受体在AD的发病中可能占有重要地位。

Objective To observe the expression differences of AMPA receptor in hippocampal neurons between SAMP8 and SAMR1 and to explore the pathogenesis of Alzheimer＇ S disease （AD）. Methods Male SAMP8 mice of 10- month old were taken as animal model of AD and SAMR1 mice were taken as control group. Morris water maze （MWM） , electron microscope and western blotting were used in this study. Results Comparing with the control group, the model group had significant learning impairment and memory retention deficits. The thickness of post synaptic density（PSD） and the curvature of the synaptic interface in the model group dicrease. The width of synaptic cleft in the model group increased. The expression of GluR2 in the model group dicreased. There were no significant differences in the expression of GluR1 between two groups. Conclusions Impaired synaptic plasticity mediated by pathological alteration of AMPA receptor in hippocampus mey be the pathogenesis underlying learning and memory disorders of AD.