阿尔茨海默病小鼠Wnt信号通路相关蛋白表达水平及意义

Expression and significance of Wnt signaling pathway in mice with Alzheimer’s disease

目的分析阿尔茨海默病(AD)小鼠Wnt信号通路相关蛋白表达水平及意义。方法 96只C57小鼠随机分为实验组和对照组,每组48只。实验组为APP/PS1双转基因小鼠,分为1、3、5及12月龄4组(对应月龄处死),每组12只;对照组为正常C57小鼠,也分为1、3、5及12月龄4组,每组12只。通过Morris水迷宫实验进行学习能力和记忆训练测试。处死小鼠获取脑组织海马标本,观察海马区病理变化。Western blotting检测Wnt信号通路相关蛋白β-连环蛋白(β-catenin)、糖原合成酶激酶-3β(GSK-3β)及海马区突触前蛋白(Synapsin1)、海马区突触后蛋白95(PSD-95)表达水平。结果实验组1、3、5及12月龄小鼠逃避潜伏期、首次跨越原平台时间逐渐延长(P<0.05);且实验组均较对照组同月龄延长(P<0.05)。实验组小鼠随着月龄增加,其细胞数量减少、体积缩小、间隙扩大现象越明显,颗粒细胞及锥体细胞破坏现象越严重,锥体细胞树突均变短。实验组1、3、5及12月龄小鼠β-catenin、GSK-3β蛋白表达水平依次降低,Synapsin1及PSD-95表达水平亦依次降低(P<0.05)。实验组均较对照组同月龄小鼠β-catenin、GSK-3β、Synapsin1及PSD-95蛋白表达水平降低(P <0.05)。结论 AD小鼠Wnt信号通路β-catenin、GSK-3β蛋白表达水平下降,可能与其海马区病理变化及突触前后蛋白表达水平下降相关,Wnt信号通路的失活可能加快AD病理过程。

Objective To analyze the molecular expression level and significance of Wnt signaling pathway in mice with Alzheimer’s disease(AD). Methods C57 mice were randomly divided into the experimental group and the control group(n = 48). Animals in the experimental group were APP/PS1 double-transgenic mice and normal C57 mice in control group. Mice at the age of 1 month, 3 months, 5 months and 12 months(n = 12) were sacrificed.The learning ability and memory training tests were performed through the Morris water maze. The hippocampus samples were collected to observe the pathological changes in the hippocampus. Expression levels of Wnt signaling pathway associated proteins β-catenin, glycogen synthase kinase-3β(GSK-3β), hippocampus synaptophysin and postsynaptic density protein 95(PSD-95) were detected by Western blotting. Results The escape latency and the time for crossing the original platform of were increased along with aging(P < 0.05), which was more dramatic in experimental group when compared with those in control group. and they were longer than those of corresponding mice in the control group(P < 0.05). With the increase of age in the experimental group, decrease of cell amount and volume, the expand of gap, destruction of granular cells and pyramidal cells, and shorten of the dendrites of pyramidal cells were getting more obvious(P < 0.05). Expression levels of β-catenin, GSK-3β protein, presynaptic protein Synapsin1 and postsynaptic protein PSD-95 in the hippocampus were decreased along with aging in the experimental group(P < 0.05), which was more obvious when compared with those in control group(P < 0.05).Conclusions Lowered activation of Wnt signaling pathway in AD mice may promote the pathological progression of AD.