miR-377-3p调控Zfp462/Pbx1信号通路参与孕期缺氧子代焦虑样行为

胎儿宫内缺氧是产科最常见的并发症之一，与许多神经系统疾病如焦虑、认知障碍等密切相关，但其内在机制尚不清楚。我们前期研究发现Zfp462（+/-）小鼠表现出严重焦虑样行为；而孕期缺氧子代小鼠出生时低体重，成年后也存在焦虑样行为伴随Zfp462表达降低和miR-377-3p表达升高。我们预实验结果提示miR-377-3p能够结合到Zfp462的3'-UTR调控Zfp462表达，而Zfp462有调控增殖相关基因Pbx1启动子的功能。由此我们提出假说：miR-377-3p调控Zfp462/Pbx1信号通路参与孕期缺氧子代焦虑样行为。本课题将利用分子生物学、细胞生物学以及神经生物学等方法阐明miR-377-3p对Zfp462/Pbx1信号通路的调控，揭示孕期缺氧如何通过该表观遗传学信号通路影响子代焦虑样行为，探索miR-377-3p/Zfp462作为孕期缺氧子代焦虑症生物学标记物和临床转化的可能性。

Intrauterine hypoxia is one of the most common obstetric complications, which is closely related to many nervous system diseases such as anxiety and cognitive impairment, however its internal mechanism is still unclear. Our previous study found that Zfp462 (+/-) mice showed severe anxiety-like behavior, and the offspring of pregnant mice with hypoxia had low birth weight and anxiety-like behavior in adulthood, accompanied by the decrease of Zfp462 expression and the increase of mir-377-3p. Our preliminary results suggested that mir-377-3p can bind to the 3'-UTR of Zfp462 and regulate the expression of Zfp462, and Zfp462 could regulate the Pbx1 promoter. Therefore, we hypothesize that mir-377-3p regulates anxiety-like behavior in offspring exposed to prenatal hypoxia through Zfp462/Pbx1 signaling pathway. In this project, molecular biology, cell biology and neurobiology methods will be used to clarify the regulation of mir-377-3p on Zfp462/Pbx1 signaling pathway, reveal how hypoxia during pregnancy affects anxiety-like behavior of offspring through this epigenetic signaling pathway, explore the possibility of mir-377-3p/Zfp462 as a biomarker and clinical transformation of anxiety disorder in hypoxia offspring during pregnancy.