催产素通过PVN-mPFC神经环路调控RGS2表达在产后抑郁大鼠模型中的作用及机制研究

产后抑郁（PPD）严重影响母婴身心健康，由于经历孕期激素剧烈波动的特殊生理过程，发病机制复杂且不明，尚缺乏经济有效的治疗靶点及手段。PPD患者血浆催产素（OXT）水平显著降低，而我们已有研究也表明，PPD大鼠室旁核（PVN）内OXT水平显著降低，但降低的机制及在PPD中的作用不清。我们采用孕期应激PPD模型发现，PVN-mPFC是OXT参与PPD发病的主要环路，OXT激活受体后影响与抑郁相关的G蛋白调节因子2（RGS2）表达。因此，我们提出假说，PVN内降低的OXT通过与受体结合影响mPFC内RGS2的表达进而在PPD发生中起关键作用。本项目将结合基因敲除动物，采用行为学、电生理、光遗传、病毒等手段，在动物及细胞水平，探索PPD发生中OXT下降机制、研究OXT/ORTR对RSG2的调控、及二者在PPD中的作用机制。本项目将为解析PPD的发病机制提供新线索、并为PPD的诊疗提供新思路和靶点。

Postpartum depression (PPD) seriously affects the physical and mental health of mother and baby. PPD lacks of economic, effective therapeutic targets and means due to severe hormonal fluctuations during pregnancy. The pathogenesis of PPD is complex and undefined. The plasma oxytocin (OXT) levels decreased significantly in PPD patients, and our previous studies have shown that OXT levels also decreased significantly in the paraventricular nucleus (PVN) of PPD rats, but the role of OXT in PPD were unclear. Furthermore, we found that PVN-mPFC was the main circuit of OXT involving in PPD pathogenesis and OXT receptor activation affected depression related RGS2 expression in pregnancy-induced stress PPD model. Therefore, we propose the hypothesis that reduced OXT binding to the receptor in PVN affect RGS2 expression in mPFC in PPD model. This project will explore the mechanism of OXT decline in PPD, the regulation of OXT/ORTR on RSG2, and the implied mechanism of them in PPD pathogenesis using PPD rats, gene knockout animals and cells combined with behavioral, electrophysiological, optogenetics, virus techniques. The project will provide new clues for PPD pathogenesis and new ideas and targets for PPD diagnosis and treatment.