REST/NRSF对皮质酮应激模型小鼠抑郁与焦虑样行为影响  

Effect of REST/NRSF on depression-and anxiety-like behavior in repeated corticosterone injected mice

作　　者：余煊 李祥磊 孙秀萍 秦川 YU Xuan;LI Xianglei;SUN Xiuping;QIN Chuan(Institute of Medical Laboratory Animal Sciences,Chinese Academy of Medical Sciences(CAMS),Comparative Medicine Center,Peking Union Medical College(PUMC),National Human Disease Animal Model Resource Center,NHC Key Laboratory of Human Disease Comparative Medicine,Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases,Beijing 100021,China)

机构地区：[1]中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,国家人类疾病动物模型资源库,卫健委人类疾病比较医学重点实验室,北京市人类重大疾病实验动物模型工程技术研究中心,北京100021

出　　处：《中国实验动物学报》2021年第6期707-714,共8页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金资助项目(81801333)。

摘　　要：目的研究REST在皮质酮模型小鼠中的表达情况及REST表达上调时对小鼠抑郁与焦虑行为影响,探索其在小鼠抑郁模型中的作用。方法重复皮下注射皮质酮建立小鼠慢性应激模型,利用AAV病毒载体过表达小鼠脑内REST,行为学检测小鼠抑郁与焦虑表型变化,并用实时荧光定量PCR探索REST对相关基因的影响。结果重复皮下注射皮质酮4周能够显著降低小鼠体重(P<0.01),诱导小鼠抑郁样行为。海马区过表达REST影响模型小鼠在抑郁和焦虑行为学测试中的表现,缓解抑郁样表型,降低模型小鼠在悬尾实验和强迫游泳实验中的不动时间;诱导焦虑症状,进入旷场中央区的次数减少,对高架十字迷宫封闭臂的探索次数和停留时间增加;同时能够调节Bndf、Nt3、Ngf、Fgf2的RNA转录水平。结论REST在皮质酮应激抑郁模型中起着双向调控作用,并不是单一缓解抑郁行为,其机制可能与其参与调节表达的多种基因及信号通路综合作用相关。Objective This research investigated the expression of REST in repeated corticosterone injected mice and the effects of REST on depression-and anxiety-like behaviors in model mice.Methods A chronic stress mouse model was established by repeated subcutaneous injections of corticosterone.An AAV virus vector overexpressing REST was injected into the hippocampus of the mouse brain.Then,the depression-and anxiety-like behaviors of mice were assessed by several behavioral tests.Finally,we detected the expression of REST-related genes by real-time RT-PCR.Results Repeated subcutaneous injections of corticosterone for 4 weeks successfully induced depression-like behavior and reduced body weight in mice(P<0.01).REST overexpression in the hippocampus influenced the performance of model mice in the depression and anxiety behavioral tests.Specifically,it reduced the immobility time of model mice in the tail suspension test and forced swimming test and the number of entries into the central area in the open field test.In addition,REST overexpression increased the exploration frequency and residence time in the enclosed arms of the elevated cross maze.The RNA transcription levels of Bndf,Nt3,Ngf and Fgf2 were also affected in model mice after REST overexpression.Conclusions REST plays a bidirectional role in the corticosterone-induced depression mouse model.Its mechanism may be related to its participation in the regulation of multiple target genes and the comprehensive effect of different signaling pathways.

关 键 词：抑郁症 动物模型 行为学测试 腺相关病毒 转录调控因子 

分 类 号：Q95-33[生物学—动物学]