慢性社交挫败应激小鼠大脑的C-U RNA编辑  

C-U RNA editing in the mouse brain under chronic social defeat stress

作　　者：任春艳 魏志远 饶军华 饶义剑 陈建欢 REN Chunyan;WEI Zhiyuan;RAO Junhua;RAO Yijian;CHEN Jianhuan(Wuxi School of Medicine,Jiangnan University,Wuxi 214122,Jiangsu Province,P.R.China;School of Biotechnology,Jiangnan University,Wuxi 214122,Jiangsu Province,P.R.China;Joint Primate Research Center for Chronic Diseases of Jiangnan University&Institute of Zoology of Guangdong Academy of Sciences,Jiangnan University,Wuxi 214122,Jiangsu Province,P.R.China;Institute of Zoology of Guangdong Academy of Sciences,Guangzhou 510260,Guangdong Province,P.R.China)

机构地区：[1]江南大学无锡医学院,江苏无锡214122 [2]江南大学生物工程学院,江苏无锡214122 [3]江南大学-广东科学院动物研究所“慢性病灵长类研究联合实验室”,江苏无锡214122 [4]广东科学院动物研究所,广东广州510260

出　　处：《深圳大学学报（理工版）》2021年第5期510-516,共7页Journal of Shenzhen University(Science and Engineering)

基　　金：国家自然科学基金资助项目(31671311);广东省自然科学基金资助项目(2019A1515012062);中央高校基本科研业务费专项资金(JUSRP51712B,JUSRP1901XNC);江南大学研究生培养创新工程项目(KYCX201946);无锡“太湖人才计划”创新领军人才项目

摘　　要：核糖核酸(ribonucleic acid,RNA)编辑与应激、神经系统疾病和精神疾病有关,然而胞苷到尿苷(C-U)的RNA编辑与慢性社交挫败应激(chronic social defeat stress,CSDS)的相关性尚未明确.分析小鼠大脑奖赏关键区——腹侧被盖区(ventral tegmental area,VTA)中存在的C-U编辑,及其在情绪应激(emotional stress,ES)或生理应激(physical stress,PS)下的社交挫败模型中的变化.结果发现,在成年雄性小鼠VTA内约16198个高置信度编辑位点存在C-U编辑.其中,48个位点具有显著组间差异RNA编辑水平,其主成分分析显示,主成分1的贡献率达到了51.78%.此外,ES组、PS组和对照组中分别有307、223和301个位点特异地存在于组内的多个样本中,并在与中枢神经系统相关的基因功能方面呈现差异化的富集.更重要的是,作为应激的重要相关因子,血清和糖皮质激素依赖性激酶1基因在ES组中特异性地表达显著上调,同时其mRNA也在ES中存在特异的编辑.研究结果证明,CSDS小鼠模型大脑VTA中存在明确的C-U RNA编辑改变,且可能参与CSDS相关的潜在分子机制.Existing studies suggest that RNA editing is associated with stress,neurological diseases and psychiatric disorders.However,the role of C-U RNA editing in chronic social defeat stress(CSDS)remains unclear.The current study herein analyzed mRNA C-U editing in the brain ventral tegmental area(VTA),a key brain reward region,and its changes in mouse models of CSDS under emotional stress(ES)or physiological stress(PS)conditions compared to controls.Our results discovered and validated C-U editing at 16198 high confidence editing sites in adult male mouse VTA.Among them,48 sites showed differential RNA editing levels among the three groups.Principal component analysis revealed 51.78%contribution from principle component 1(PC1)to the variance.In addition,there were 307,223,and 301 sites repeatedly observed in intra-group samples in ES,PS and control groups,respectively,and which were enriched in different gene functions.Moreover,a key factor previously reported to be involved in stress,serum/glucocorticoid regulated kinase 1(Sgk1)gene was specifically upregulated and its mRNA was also specifically edited in ES.These results demonstrate dynamic C-U RNA editing in the brain VTA of mouse models of CSDS,which further suggests that C-U RNA editing is a potential molecular mechanism related to CSDS.

关 键 词：神经生物学 核糖核酸编辑 社交挫败 情绪应激 生理应激 腹侧被盖区 抑郁 创伤后应激障碍 

分 类 号：Q819[生物学—生物工程] R749[医药卫生—神经病学与精神病学]