Cdk5/p25在APPswe/PS1dE9双转基因AD模型小鼠海马内表达与认知功能障碍的关系

Relationship between hippocampal expression of Cdk5/p25 and cognitive dysfunction in APPswe/PS1dE9 double transgenic model mice with Alzheimer′s disease

目的观察APPswe/PS1dE9双转基因阿尔茨海默病模型小鼠认知功能的变化,探讨其与海马细胞周期蛋白依赖性蛋白激酶5及其激动因子细胞周期蛋白(Cdk5/p25)表达的关系。方法通过Morris水迷宫观察3、6、9月龄APPswe/PS1dE9双转基因小鼠和同种野生型小鼠学习记忆能力的变化;采用western blotting法及免疫组织化学染色法检测其海马内Cdk5/p25的表达水平。结果通过Morris水迷宫训练发现,3月龄APPswe/PS1dE9双转基因小鼠学习记忆能力与同月龄野生型小鼠比较,差异无统计学意义(P>0.05);而6、9月龄APPswe/PS1dE9双转基因小鼠较同月龄野生型小鼠定位航行实验潜伏期逐渐延长,差异有统计学意义(P<0.05)。Western blotting结果显示,6、9月龄APPswe/PS1dE9双转基因小鼠海马内Cdk5/p25的表达水平较同月龄野生型小鼠增高,差异均有统计学意义(P<0.05)。免疫组织化学染色结果显示,6、9月龄APPswe/PS1dE9双转基因小鼠海马内Cdk5阳性细胞的表达与同月龄野生型小鼠比较,差异有统计学意义(P<0.05);且随着年龄的增长,APPswe/PS1dE9双转基因小鼠海马内Cdk5阳性细胞表达逐渐增多,差异有统计学意义(P <0.05)。结论APPswe/PS1dE9双转基因小鼠学习记忆能力的下降与Cdk5/p25活性异常表达有关。

Objective To observe the relationship of the hippocampal expressions of Cdk5/p25 and the change of cognitive function in APPswe/PS1dE9 double transgenic model mice with Alzheimer′s disease(AD).Methods The learning and memory abilities of APPswe/PS1dE9 double transgenic mice with AD aged 3,6 and 9 months and wild-type mice were observed by Morris water maze;the hippocampal expression level of Cdk5/p25 was detected by western blotting and immunohistochemical staining.Results There was no difference between APPswe/PS1dE9 double transgenic mice with AD aged 3 month and wild-type mice of the same age in the learning and memory abilities(P>0.05).At aged 6 months and 9 months,compared with the wild-type,the mean latency in place navigation test of APPswe/PS1dE9 double transgenic mice with AD were prolonged,the differences were statistically significant(P<0.05).Western blotting results showed that the hippocampal expression level of Cdk5/p25 of APPswe/PS1dE9 double transgenic mice with AD were higher than those of wild-type mice at aged 6 months and 9 months,the differences were statistically significant(P<0.05).Immunohistochemistry showed that the hippocampal expressions of Cdk5/p25 of Cdk5 positive cells of APPswe/PS1dE9 double transgenic mice with AD mice were compared with those of wild-type mice at aged 6 months and 9 months,the differences were statistically significant(P<0.05);and the hippocampal expression of Cdk5 positive cells of APPswe/PS1dE9 double transgenic mice with AD increased with age increased,the differences were statistically significant(P<0.05).Conclusion The decreased learning and memory abilities of APPswe/PS1dE9 the double transgenic mice have relationship with the upregulation of Cdk5/p25 in hippocampus.