慢性社交挫败应激小鼠大脑的C-U RNA编辑

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

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

C-U RNA editing in the mouse brain under chronic social defeat stress
REN Chunyan1, 2, 3, WEI Zhiyuan1, 3, RAO Junhua4, RAO Yijian2, and CHEN Jianhuan1, 3

1)Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu Province, P.R.China;2)School of Biotechnology, Jiangnan University, Wuxi 214122, Jiangsu Province, P.R.China;3)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;4)Institute of Zoology of Guangdong Academy of Sciences, Guangzhou 510260, Guangdong Province, P.R.China

neurobiology; RNA editing; social defeat; emotional stress; physical stress; ventral tegmental area; depression; post-traumatic stress disorder

DOI: 10.3724/SP.J.1249.2021.05510

备注

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16 198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 16 198 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.
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