α7nAchR基因713T>C突变对AD小鼠认知功能和Aβ表达的影响

Effect of α7nAchR gene 713T>C mutation on cognitive function and Aβ expression in AD mice

目的探讨α7nAchR基因713T>C突变对阿尔茨海默病(AD)小鼠认知功能和脑内β淀粉样蛋白(Aβ)表达的影响。方法将6个月龄敲除α7nAchR基因的APPSwe转基因小鼠(APPa7KO小鼠)20只按随机数字表法分为两组(突变型组和野生型组),每组10只,分别在小鼠侧脑室注射突变型和野生型AVV-α7nAchR cDNA,1次/月,共6次。小鼠满12个月龄时采用Morris水迷宫检测小鼠认知功能的变化,ELISA法检测小鼠Aβ40、Aβ42表达水平,免疫组织化学染色检测小鼠Aβ斑沉积情况。结果与野生型组小鼠相比,突变型组小鼠的逃避潜伏期和初次找到平台的时间延长,海马Aβ40、Aβ42表达水平显著升高,差异均有统计学意义(P<0.05)。结论α7nAchR基因713T>C突变加重了AD小鼠的认知功能损害和海马神经元Aβ表达水平。

Objective To investigate the effect of α7nAchR gene 713T〉C mutation on the cognitive function and Aβ expression in Alzheimer＇s disease（AD） mice. Methods Twenty APPSwe transgenic APPaTKO mice（6 months old,α7nAchR gene knockout ） were divided into the mutation type group and wild type group according to the random number table method, 10 cases in each group. The mutation type and wild type of AVV-α7nAchR cDNA were respectively injected by lateral ventricle,once per month, for 6 times. The change of cognitive function in mice was examined by Morris water maze. The ELISA method was used to detect Aβ 40 and Aβ 42 expression levels. The Aβ plaque deposit situation was detected by the immunochemical method. Results Compared with the mice in the wild type group, the escape latency and the time of first time to find the platform of the mice in the mutation type group were significantly extended,while Hippocampal Aβ40 and Aβ42 expression levels were significantly increased, the difference was statistically significant（P〈0.05）. Conclusion α7nAchR gene 713T〉C mutation aggravates the cognitive function impairments in AD mice and hippocampal neuron Aβ expression level.