慢性应激中CRFR1/PKA对雌性APP/PS1转基因小鼠的影响  

Effects of CRF/PKA expression on chronic stressed APP/PS1 transgenic female mice

作　　者：颜彦 雷晓露 赵真婉 王甸北 陈远寿 董红心 Yan Yan;Lei Xiaolu;Zhao Zhenwan;Wang Dianbei;Chen Yuanshou;Dong Hongxin(Guizhou Key Laboratory of Anesthesia and Organ Protection,Zunyi Medical University,Zunyi Guizhou 563099,China;Guizhou Key Laboratory of Brain Science,Zunyi Guizhou 563099,China;Department of Surgery Hepatological,Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563099,China;Department of Physiology,Zunyi Medical University,Zunyi Guizhou 563099,China;Department of Psychiatry and Behavioral Sciences,Northwestern University,Chicago 60611,USA)

机构地区：[1]遵义医科大学贵州省麻醉与器官保护基础研究重点实验室,贵州遵义563099 [2]贵州省普通高等学校脑科学特色重点实验室,贵州遵义563099 [3]遵义医科大学附属医院肝胆外科,贵州遵义563099 [4]遵义医科大学生理学教研室,贵州遵义563099 [5]西北大学芬伯格医学院精神病学与行为科学系,美国芝加哥60611

出　　处：《遵义医科大学学报》2023年第3期258-263,共6页Journal of Zunyi Medical University

基　　金：贵州省教育厅青年科技人才成长项目,NO:黔教合KY字[2018]241。

摘　　要：目的运用APP/PS1转基因小鼠建立慢性应激模型,观察CRFR1/PKA在不同性别中的影响。方法选取C57/BL6j和APP/PS1转基因小鼠分别建立WT组(n=10)、APP组(n=10)和CUMS-APP组(n=10),利用血清皮质酮检测、旷场实验观察小鼠焦虑样变化,通过新奇物体识别实验、水迷宫观察小鼠空间学习和记忆模式改变情况,运用Western blot检测各组小鼠APP、CRFR1、PKA在海马和皮层的蛋白表达量变化。结果慢性应激后CUMS-APP组小鼠较WT组出现明显焦虑样改变(P<0.05),且应激后CUMS-APP模型组较WT组有明显认知功能障碍行为学表现(P<0.05),与APP-F组相比,CUMS-APP-F组APP、CRFR1、PKA在海马和皮层中表达出现明显升高(P<0.05)。结论慢性应激后APP/PS1雌性小鼠出现认知行为障碍及Aβ病理改变可能由CRFR1/PKA通路过度表达介导。Objective To demonstrate that sex differences impact expression of CRF/CRFR1 signaling pathway in CUMS APP/PS1 mice model.Methods Randomly selected C57/BL6j and APP/PS1 transgenic mice to establish WT group(n=10),APP group(n=10)and CUMS-APP group(n=10)respectively.To detect those mice anxiety like behavior by open field test and measure serum corticosterone concentration.In order to observe the spatial and reference memory function,we use Morris water maze and novel object recognition test.Using Western blot to measure expression of APP、CRFR1、PKA in hippocampus and cortex.Results In this study,we found that CUMS-APP group compare with WT group showed significant anxiety-like behavior changes(P<0.05),meanwhile,CUMS-APP group showed significant memory function deficits compare with WT group(P<0.05).Furthermore,the expression of APP、CRFR1、PKA in hippocampus and cortex were significantly increased in CUMS-APP-F compare with APP-F(P<0.05).Conclusion The over expression of CRFR1/PKA singling pathway may mediate memory function deficits and Aβrelated pathological changes in chronic stressed APP/PS1 transgenic female mice.

关 键 词：促肾上腺皮质激素释放激素 促肾上腺皮质激素释放激素受体-1 慢性应激 阿尔茨海默病 性别差异 

分 类 号：Q42[生物学—神经生物学] R74[生物学—生理学]