雌激素受体α基因敲除对小鼠认知功能的影响机制  

Cognitive decline in estrogen receptor α knockout mice

作　　者：王继申 竺晓鸣[2] 石纯[1] 龙大宏[1] 

机构地区：[1]广州医科大学人体解剖学教研室,广东广州510182 [2]澳门科技大学

出　　处：《解剖学研究》2014年第5期347-349,共3页Anatomy Research

基　　金：国家自然科学基金面上项目和青年项目(81370395;81200846);广东省自然科学基金博士启动项目和面上项目(S2012040007858;S2013010014468)

摘　　要：目的探讨ERα调节小鼠认知功能的作用及可能机制。方法将6只8～12周龄ERa基因敲除鼠和6只同周龄野生型小鼠分为2组：正常对照组和ERα基因敲除组。用水迷宫检测这2组小鼠的认知功能；ELISA法检测脑内Aβ含量；免疫组化法检测脑内Aβ沉淀情况。结果定位航行实验显示：与正常对照小鼠相比，ERα基因敲除鼠的逃避潜伏期显著延长（P〈O．01）；空间探索实验显示：ERα基因敲除鼠在目标象限的游泳距离占总的游泳距离的比例低于正常对照小鼠（P〈0．01）ELISA和免疫组化显示：与正常对照小鼠相比，ERα基因敲除鼠脑内Aβ生成增加（P〈0．01）。结论ERα基因敲除可导致认知功能下降，其机制可能与脑内Aβ生成增多有关。ERα基因敲除小鼠表现出类似阿尔芡海默病（AD）的病理以及行为学特征，提示其可以作为一种研究AD及其干预措施的新的动物模型。Objective This study aimed to testify the effect of ERa on the cognitive function. Methods Six 5-month old ERα knockout mice and 6 5-month old wide-type mice were divided into 2 groups, i.e., normal control group and ERα knockout group. The cognitive function of animals was tested by Morris maze. Aβ levels in mouse brain were tested by ELISA. Aβ deposit in mouse brain was analyzed by immunohistology. Results Compared with normal control group, ERα knockout groups showed a longer escape latency of place navigation and a lower percentage of swimming distance in the target quadrant （P〈0.01）. Both ELISA and Immunohistologic analysis showed that Aβ levels in ERα knockout group were higher than that in normal control group （P〈0.O1）. Conclusion ERα knockout-induced cognitive decline is associated with the increase of Aβ in the brain. ERα knock- out mice showed Alzheimer＇s-like brain pathology with spatial learning deficits and may be used as a novel animal model of AD.

关 键 词：雌激素受体Α Β淀粉样蛋白 认知功能 阿尔茨海默病 

分 类 号：R749.16[医药卫生—神经病学与精神病学]