The involvement of Notch1 signaling pathway in mid-aged female rats under chronic restraint stress. (1st November 2020)

• Record Type: Journal Article
• Authors: Shen, Jianying; Lin, Ling; Liao, Linghong; Liang, Wenna; Yang, Xiaoting; Lin, Kaimin; Ke, Long; Zhang, Lingyuan; Kang, Jie; Ding, Shanshan; Li, Candong; Zheng, Zhihong
• Is Part Of: Neuroscience letters. Volume 738(2020)
• Publication Date: 2020-11-01
• Subjects: Chronic restraint stress -- Hippocampus -- Prefrontal cortex -- Notch1 signaling pathway -- DNA methylation; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2020.135313
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: CRS induced depression-like and anxiety-like behaviors with hyperactivity of HPA in the mid-aged female rats. The mRNA and protein expression of several Notch signaling related genes were downregulated in the HIP and PFC of the mid-aged stressed female rats. DNA promotor methylation may not be an upstream cause of Notch signaling expression changes in the mid-aged stressed female rats. Abstract: 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.