APP／PSI双转基因小鼠的认知功能与海马SUMO化修饰变化

Changes on cognitive function and SUMO modification in hippocampus of APP/PS1 transgenic mice

目的观察APP／PS1双转基因小鼠的认知功能及其海马组织小分子泛素样相关修饰物（SUM0）修饰水平的变化。方法选取3月龄和16月龄的淀粉样前体蛋白／早老素（APP／PS1）双转基因小鼠及同月龄野生型小鼠，应用Morris水迷宫测试其认知功能，应用实时定量PCR和免疫组织化学技术检测其海马组织中的SUM01，2，3和SUM0特异性蛋白酶（SENPs）SENP1，2，3的基因及蛋白表达情况。结果与3月龄小鼠不同，16月龄APP／PS1双转基因小鼠的潜伏期延长，穿台次数、路程和时间百分比明显小于同月龄野生型小鼠，海马组织SUM01，3基因的表达量明显低于野生型小鼠，而SENP1，3基因的表达量明显高于野生型小鼠。结论APP／PS1双转基因小鼠的认知功能障碍可能与SUM0修饰水平下降有关。

Objective The present study was to investigate changes of cognitive function and SU- MO modification in hippocampus of APP/PS1 transgenie mice. Methods The 3 -- month-- old and 16- month-old APP/PS1 transgenie mice and the age--matched wild--type mice were selected as experi- mental animals. Morris water maze trials were used to examine the cognitive function. Real--time PCR and immunohistochemical staining were used to investigate the expression of genes and proteins （SU- MO1,SUMO2,SUMO3,SENP1,SENP2,SENP3） in the hippocampus. Results Compared with that of the wild--type mice, the latency time was prolonged, and the number of platform crossing, the distance percent and the time percent in the target quadrant all decreased in the 16--month old APP/PS1 trans- genic mice. The expression of SUMO1 and SUMO3 genes decreased; however, the expression of SENP1 and SENP3 genes increased in the 16--month old APP/PS1 transgenic mice. Conclusions The cognitive impairment of the APP/PS1 transgenic mice may be related to the decrease of the SUMO modification level.