miR-30c通过调节海马神经发生对APP/PS1转基因小鼠学习记忆能力的影响  

Effects of miR-30c on learning and memory of APP/PS1 transgenic mice through regulating hippocampal neurogenesis

作　　者：孙婷婷 董树燕[1,2] 李鲁萍 赵传华 李天鹏 Sun Tingting;Dong Shuyan;Li Luping;Zhao Chuanhua;Li Tianpeng(College of Food Science and Pharmaceutical Engineering,Zaozhuang University,Zaozhuang 277160,China;Zaozhuang Key Laboratory of Research in Neurodegenerative Diseases and Development of Neuropharmaceuticals,Zaozhuang University,Zaozhuang 277160,China;College of City and Architecture Engineering,Zaozhuang University,Zaozhuang 277160,China)

机构地区：[1]枣庄学院食品科学与制药工程学院,枣庄277160 [2]枣庄学院枣庄市神经退行性疾病与神经药物研发重点实验室,枣庄277160 [3]枣庄学院城市与建筑工程学院,枣庄277160

出　　处：《解剖学杂志》2022年第3期228-233,共6页Chinese Journal of Anatomy

基　　金：国家自然科学基金(81701389);山东省自然科学基金重点项目(ZR2020KH022);枣庄学院“青檀学者”优秀青年人才项目;枣庄学院博士启动项目(2019BS015)。

摘　　要：目的:探讨miR-30c通过调控海马神经发生对APP/PS1转基因小鼠的学习记忆的影响。方法:用免疫荧光检测Ki67的表达和Morris行为学检测APP/PS1转基因小鼠海马的神经发生及学习记忆能力,并通过脑立体定位技术显微注射miR-30c过表达和miR-30c敲减慢病毒载体以干扰海马齿状回区域的神经发生,检测海马神经发生对学习记忆的影响。结果:APP/PS1转基因小鼠的海马神经发生和学习记忆能力明显低于野生小鼠。然而,当APP/PS1转基因小鼠海马的miR-30c过表达后,海马神经发生明显增加(14.2倍);相反,当海马miR-30c敲减后,海马神经发生明显降低(0.25倍),并且Morris行为学结果显示,miR-30c敲减后小鼠的学习记忆能力明显降低,而miR-30c过表达后小鼠的学习记忆能力明显增强。结论:miR-30c可能通过调控海马神经发生影响学习记忆功能,提示miR-30c可作为干预阿尔茨海默症神经发生与学习记忆能力的潜在靶点。Objective:To investigate the effect of miR-30c on learning and memory of APP/PS1 transgenic mice through regulating the hippocampal neurogenesis.Methods:The immunofluorescence staining of Ki67 cells was detected to investigatethe hippocampal neurogenesis,and Morris maze was adopted to detect the learning and memory of APP/PS1 transgenic mice.With the method of stereological localization and miR-30c over-expression and miR-30c knockdown lentiviruses were microinjected into the dentate gyrus of hippocampi to modulate the neurogenesis.Results:The hippocampal neurogenesis,and learning and memory capacity of APP/PS1 transgenic mice were strikingly lower than that of the wild type mice.However,when miR-30c was overexpressed in the hippocampi of APP/PS1 transgenic mice,the hippocampal neurogenesis was evidently increased(14.2 fold);In contrast,when miR-30c was knocked down in the hippocampi of APP/PS1 transgenic mice,the hippocampal neurogenesis was prominently decreased(0.25 fold).Moreover,results of Morris maze demonstrated that when miR-30c in hippocampi of APP/PS1 transgenic mice was knocked down the learning and memory capacity was significantly declined,when miR-30c in hippocampi of APP/PS1 transgenic mice was overexpressed,the learning and memory capacity was obvious increased.Conclusion:miR-30c probably influence learning and memory through regulating hippocampal neurogenesis,indicating that miR-30c might be a potential therapeutic target for modulating neurogenesis,and learning and memory capacity of Alzheimer’s diseases.

关 键 词：miR-30c 神经发生 学习记忆 阿尔茨海默病 APP/PS1转基因小鼠 

分 类 号：R749.16[医药卫生—神经病学与精神病学]