MircoRNA调控海马SSTR2参与应激抗逆的机制研究

Stress and trauma affect individuals differently. While traumatic experience leads to stress-related disorders in some,and others produce stress resilience. Envidence have shown that SSTR2 in hippocampus GCL plays an important role in stress resilience. MicroRNAs (miRNAs) are endogenous regulatory mechanism in organisms by affecting gene regulation, which has not been studied in stress resilience. we detect altered hippocampus GCL miRNAs expression profile and identified miR-193、361 which bind the 3' UTR of target mRNAs. This project intends to study the suppression or overexpression of the hippocampal GCL miR-193、361 induce changes and relations of stress sensitivity,SSTR2 and neurotransmitter expression in an vivo animal model and primary cultured hippocampal neurons, Thus Further Confirmed that the phenomenon can be hereditary in an animal model. In conclusion, this project aimed to clarify the mechanism of miRNAs regulate hippocampal GCL SSTR2 gene in the process of stress resilience from the molecular、cellular as well as vivo animal model level and provide experimental and theoretical basis for preventing、finding new targets and drug design of stress-related disorders.

不同个体对外源应激反应不同，部分个体应激后易患应激相关疾病，另一部分则产生应激抗逆。已知海马GCL区SSTR2在应激抗逆过程中扮演重要角色。MicroRNA(miRNA)是机体对基因表达调控的内源性自然方式, 其与应激抗逆的关系尚未见报道。申请人预实验已找出应激抗逆与对照组中差异表达的miRNA，并从中筛选出与SSTR2 3′UTR结合的miR-193、361。本项目拟在整体动物水平研究抑制或过表达海马GCL区miR-193、361后应激抗逆鼠应激敏感性改变，探讨应激抗逆鼠海马GCL区这二种miRNA表达与SSTR2、神经递质改变的内在联系；进一步证实该现象的可遗传性；在细胞水平证实抑制或过表达这二种miRNA对体外培养海马神经元SSTR2与神经递质改变的影响。本项目旨在阐明miRNA调控海马GCL区SSTR2产生应激抗逆的机制，为应激相关疾病的预防、新靶点和药物设计提供实验和理论依据。

不同个体对外源应激反应不同，部分个体应激后易患应激相关疾病，另一部分则产生应激抗逆。已知海马GCL 区SSTR2 在应激抗逆过程中扮演重要角色。MicroRNA(miRNA)是机体对基因表达调控的内源性自然方式, 其与应激抗逆的关系尚未见报道。申请人预实验已找出应激抗逆与对照组中差异表达的miRNA，并从中筛选出与SSTR2 3′UTR 结合的miR-193、361。本项目发现整体动物水平研究抑制海马GCL 区miR-193、361 后应激抗逆鼠应激敏感性改变，结果表明抑制海马GCL 区miR-193、361后与SSTR2、5-HT、NE的表达水平增高；而且应激抗逆大鼠的子代F1及F2代大鼠进一步证实了该现象的可遗传性；在海马原代培养的神经元中证实过表达这二种miRNA 对体外培养海马神经元SSTR2、5-HT、NE的表达水平下降，神经元受到损伤。本项目阐明了miRNA 调控海马GCL 区SSTR2 产生应激抗逆的机制，为应激相关疾病的预防、新靶点和药物设计提供实验和理论依据。