Women are vulnerable to adverse stress events, especially during perimenopause. Substantial evidence has associated the impaired neuronal plasticity with abnormal behaviors under stressful conditions in animals. The Notch signaling pathway is critical for neuronal plasticity in the structure and function of brain areas. In this study, the mid-aged female rats were subjected to chronic restraint stress(CRS) in combination with isolated rearing for 6 weeks. The behavior tests and HPA activity were conducted to evaluate the model. The mRNA and protein levels of Notch1 signaling related genes in the hippocampus(HIP) and prefrontal cortex(PFC) were analyzed by RT-qPCR and western blotting. The promoter methylation levels were measured by bisulfite sequencing PCR analysis. CRS induced depression-like and anxiety-like behaviors in mid-aged stressed females, as shown by decreased locomotor activity, sucrose consumption and increased HPA activity. Moreover, after CRS, the rats exhibited decreased mRNA and protein levels in Jagged1, Notch1 and Hes5 in the HIP and Notch1, Hes1 and Hes5 in the PFC. However, there were no significant promotor methylation changes between the stressed and control female rats. These findings suggest that Notch1 signaling pathway may contribute to the behavioral changes following CRS in mid-aged female rats and the upstream cause of the gene expression changes needs to be further investigated.

妇女容易遭受不良压力事件，尤其是在围绝经期。大量证据表明，神经元可塑性受损与动物在压力条件下的异常行为有关。Notch信号通路对于大脑区域的结构和功能中的神经元可塑性至关重要。在这项研究中，对中年雌性大鼠进行慢性束缚应激（CRS）并单独进行饲养6周。进行了行为测试和HPA活动以评估模型。通过RT-qPCR和western blotting分析海马（HIP）和前额叶皮层（PFC）中Notch1信号传导相关基因的mRNA和蛋白水平。通过亚硫酸氢盐测序PCR分析测量启动子甲基化水平。CRS在中年压力女性中诱发抑郁样和焦虑样行为，表现为运动能力下降，蔗糖消耗减少和HPA活性增加。此外，CRS后，大鼠的HIP的Jagged1，Notch1和Hes5以及PFC的Notch1，Hes1和Hes5的mRNA和蛋白质水平降低。然而，在应激和对照雌性大鼠之间没有明显的启动子甲基化变化。这些发现表明，Notch1信号通路可能是中年雌性大鼠CRS后行为改变的原因，并且基因表达改变的上游原因有待进一步研究。HIP中的Notch1和Hes5，PFC中的Notch1，Hes1和Hes5。然而，在应激和对照雌性大鼠之间没有明显的启动子甲基化变化。这些发现表明，Notch1信号通路可能是中年雌性大鼠CRS后行为改变的原因，基因表达改变的上游原因有待进一步研究。HIP中的Notch1和Hes5，PFC中的Notch1，Hes1和Hes5。然而，在应激和对照雌性大鼠之间没有明显的启动子甲基化变化。这些发现表明，Notch1信号通路可能是中年雌性大鼠CRS后行为改变的原因，基因表达改变的上游原因有待进一步研究。