催产素受体Gαq与β-arrestins偏爱型信号通路在产后抑郁症中的作用

产后抑郁症（PPD）是以产后情感低落为特征的精神障碍，严重损害妇女身心健康。催产素受体是一种神经肽受体，可调控精神行为。星形胶质细胞炎症在抑郁症中介导神经损伤，但在PPD这种特定抑郁症中的调控暂无报道，其表达的催产素受体是否参与PPD病理机制也不清楚。申请者前期发现，PPD小鼠海马区星形胶质细胞与NLRP3炎症小体活化，催产素受体表达下调，由此推测星形胶质细胞催产素受体参与PPD神经炎症。催产素受体活化后激活Gαq与β-arrestins通路，可通过Gαq发挥抗炎作用，由β-arr介导内化脱敏，但两种偏爱型通路在PPD中的研究尚无报道。本课题拟在前期基础上，运用慢病毒脑立体定位注射及OXTR CKO、β-arr CKO鼠制备PPD模型及培养海马原代星形胶质细胞，通过动物行为学、检测炎症小体活化、催产素受体内化及降解，研究Gαq与β-arr通路在PPD中的作用，为PPD药物研发积累学术基础。

Postpartum depression (PPD) is a mental disorder characterized by low emotions after childbirth , which seriously damages women's physical and mental health. Oxytocin receptor is a kind of neuropeptide receptor, which can regulate mental behavior. Astrocytic inflammation mediates nerve damage in depression, but its regulation in PPD has not been reported yet. Whether oxytocin receptor is involved in pathology of PPD is unclear. The researcher previously found that astrocytes and NLRP3 inflammasome in hippocampus of PPD mice were activated, and expression of oxytocin receptor was down-regulated, which suggested that astrocytic oxytocin receptor was involved in neuroinflammation of PPD. Gαq and β-arrestins signaling pathways activate after oxytocin receptor is activated. Oxytocin receptor plays an anti-inflammatory role through Gαq, and β-arrestins induce the internalization and desensitization of oxytocin receptor. However, there is no report of these two biased signaling pathways in PPD. On the basis of previous studies, PPD mice with cerebral stereotactic injection of lentivirus, OXTR CKO mice, β-arrestins CKO mice were prepared, and primary hippocampal astrocytes were cultivated. Animal behavior experiments were conducted. Inflammasome activation and internalization/degradation of oxytocin receptor were detected to study the roles of Gαq and β-arrestins biased signaling pathways in PPD. This project aims to accumulate academic basis for research and development of PPD therapy.