Fmr1小鼠的跳台实验和海马哺乳动物雷帕霉素靶蛋白的关系

Expression of mTOR caused by step-down test in hippocampal of Fmr1 knockout mice

目的观察Fmr1基因敲除(KO)小鼠跳台实验行为及哺乳动物雷帕霉素靶蛋白(mTOR)的变化,探讨mTOR与KO小鼠学习记忆能力的关系。方法利用PCR技术鉴定20只4周龄FVB近交系KO及20只野生型(WT)小鼠,随机分为行为学前WT组、行为学后WT组、行为学前KO组和行为学后KO组。通过避暗实验测试行为学WT及KO组小鼠的学习记忆能力,Western blot检测各组海马区p-mTOR及mTOR表达的变化。结果跳台实验第1天KO鼠的潜伏期较WT鼠短,错误次数较WT鼠多。跳台实验第2天KO鼠的潜伏期较WT鼠短,错误次数较WT鼠多。Western blot检测显示:KO鼠空白组mTOR表达较WT鼠空白组增高(P<0.05);KO鼠空白组PmTOR与WT鼠空白组相比表达增高(P<0.05)。结论 Fmrp对mTOR信号通路具有负性调节作用;Fmr1基因敲除小鼠学习记忆能力障碍与mTOR信号通路受损有关。

Objective To observe the ability of learning and memory and the expression of mammalian target of rapamycin（mTOR）in hippocampal area of Fmr1 gene knockout（KO）mice,and explore the relationship of mTOR and the ability of learning and memory in KO mice. Methods To identify four-week-old FVB KO and wild-type（WT）mice by PCR.40 mice were divided into four groups：The blank WT group;The behavioral WT group;The blank KO group;The behavioral KO group.step-down test were chosen to assess learning and memory ability of KO and WT mice and the expression of mTOR were tested by Western blot. Results In step-down test,compared with WT mice,KO mice had shorter latency and more error counts. Western blot analysis showed that ：（1）No significant difference for the expression of mTOR and p-mTOR in hippocampal area were obtained between the blank WT group and the behavioral WT group. The same as the blank and behavioral KO group.（2）The expression of p-mTOR in hippocampal area of the behavioral KO group is increased,compared with the behavioral WT group were significantly different（P〈0.05）.（3）No significant difference for the expression of mTOR and p-mTOR in hippocampal area were obtained between the behavioral WT and KO group. Conclusion Fmrp has a negative regulatory role of mTOR signaling pathway;Cognitive dysfunction in Fmr1 gene knockout mice is related to the abnormal expression of mTOR in hippocampus.