Dang Jingjing, Kuai Huihui, Zhou Siqi, Guo Shanshan, Sheng Jingyi, Wang Zhiping
Nanjing Medical University, 210000 Nanjing, Jiangsu, China; Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, 221000 Xuzhou, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 221000 Xuzhou, Jiangsu, China.
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 221000 Xuzhou, Jiangsu, China.
Actas Esp Psiquiatr. 2025 May;53(3):504-515. doi: 10.62641/aep.v53i3.1773.
Oxytocin (OT) is a key molecule that not only acts as a uterine-contracting hormone during delivery but is also a critical maternal hormone that enables the social transmission of maternal behavior. Postpartum depression (PPD) is a series of depression-like symptoms that occur especially in women in the perinatal period and is accompanied by the failure to adapt to motherhood as well as impaired parent-infant bonding. However, the mechanism by which OT regulates PPD is still unclear. This study aimed to investigate the correlation between OT levels in the paraventricular nucleus (PVN) and PPD and to explore the potential mechanism underlying the involvement of the OT system in the regulation of PPD.
We induced perinatal chronic stress in pregnant rats to establish a PPD model. OT levels in the cerebrospinal fluid (CSF) and PVN were measured throughout the perinatal period. We administered the chemogenetic virus hM3Dq into the PVN, intraperitoneally injected N-oxyclozapine to activate OT-secreting neurons, and observed the effects of OT treatment on behaviors related to PPD. Finally, we investigated the potential mechanism underlying PPD regulation by the OT system via transmission electron microscopy, immunofluorescence (IF), and quantitative real-time PCR (qRT-PCR).
Compared with those in the normal group, CSF oxytocin levels in the postpartum depression group decreased from late pregnancy to lactation (p < 0.001). Chemogenetic activation-induced endogenous OT release in the PVN not only alleviated PPD-like symptoms in rats but also enhanced the intracellular production of OT. Transmission electron microscopy revealed an increase in the size of the Golgi apparatus, endoplasmic reticulum, and dense vesicles within OT neurons. IF and qRT-PCR revealed elevated OT levels and increased oxytocin expression within the PVN following chemogenetic activation (p < 0.01).
Lower OT levels are strongly associated with the occurrence of PPD. The release of activated OT has been shown to improve PPD-like behaviors in rats and promote intracellular OT synthesis.
催产素（OT）是一种关键分子，它不仅在分娩期间作为子宫收缩激素起作用，而且还是一种关键的母体激素，能够使母体行为进行社会传递。产后抑郁症（PPD）是一系列类似抑郁的症状，尤其发生在围产期女性中，伴有无法适应母亲角色以及母婴联结受损。然而，OT调节PPD的机制仍不清楚。本研究旨在探讨室旁核（PVN）中OT水平与PPD之间的相关性，并探索OT系统参与PPD调节的潜在机制。
我们在孕鼠中诱导围产期慢性应激以建立PPD模型。在整个围产期测量脑脊液（CSF）和PVN中的OT水平。我们将化学遗传病毒hM3Dq注入PVN，腹腔注射N-氧氯氮平以激活OT分泌神经元，并观察OT治疗对与PPD相关行为的影响。最后，我们通过透射电子显微镜、免疫荧光（IF）和定量实时PCR（qRT-PCR）研究OT系统调节PPD的潜在机制。
与正常组相比，产后抑郁症组从妊娠晚期到哺乳期脑脊液催产素水平降低（p < 0.001）。化学遗传激活诱导PVN中内源性OT释放，不仅减轻了大鼠的PPD样症状，还增强了OT的细胞内产生。透射电子显微镜显示OT神经元内高尔基体、内质网和致密囊泡的大小增加。IF和qRT-PCR显示化学遗传激活后PVN内OT水平升高且催产素表达增加（p < 0.01）。
较低的OT水平与PPD的发生密切相关。已证明激活的OT释放可改善大鼠的PPD样行为并促进细胞内OT合成。
