Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats

Abstract

Studies show that gender plays an important role in stress-related disorders, and women are more vulnerable to its effect. The present study was undertaken to investigate differences in the change in expression of brain-derived neurotrophic factor (BDNF), and its tyrosine intracellular kinase-activating receptor (TrkB) genes in the male and female rats' hippocampus (HPC) under chronic mild repeated stress (CMRS) conditions. In this experiment, male and female Wistar rats were randomly divided into two groups: the CMRS and the control group. To induce stress, a repeated forced swimming paradigm was employed daily for adult male and female rats for 21 days. At the end of the stress phase, elevated plus maze (EPM) was used for measuring the stress behavioral effects. Serum corticosterone level was measured by ELISA. BDNF and TrkB gene methylation and protein expression in the HPC were detected using real-time PCR and Western blotting. Chronic stress in the adolescence had more effects on anxiety-like behavior and serum corticosterone concentration in female rats than males. Furthermore, stressed female rats had higher methylation levels and following reduced protein expression of BDNF but not TrkB compared to stressed male rats. These findings suggest that in exposure to a stressor, sex differences in BDNF methylation may be root cause of decreased BDNF levels in females and may underlie susceptibility to pathology development.

Extracellular signal‐regulated kinase activation in the spinal cord contributes to visceral hypersensitivity induced by craniofacial injury followed by stress

“…In addition, the decrease in sucrose consumption confirmed the depression‐like behaviors in E2 replacement rats exposed to FS (E2+CFA+FS group and E2+saline+FS group) compared with rats in other groups. However, the elevated plus maze did not show any differences among different groups, suggesting that 3 day FS may be a mild, subchronic stressor which induces less severe anxiety responses compared with a chronic stressor . Using this overlapping pain model, the purpose of the study was to investigate how this mild stressor initiates the responses of the central nervous system following craniofacial muscle inflammation in E2 replacement rats.…”

“…However, the elevated plus maze did not show any differences among different groups, suggesting that 3 day FS may be a mild, subchronic stressor which induces less severe anxiety responses compared with a chronic stressor. [41][42][43] Using this overlapping pain model, the purpose of the study was to investigate how this mild stressor initiates the responses of the central nervous system following craniofacial muscle inflammation in E2 replacement rats. Chronic and other modes of stress may be used in future studies to clarify the role of stress on comorbidity between TMD and IBS.…”

Epigenetic programming of the neuroendocrine stress response by adult life stress

“…Upregulation of PVN BDNF by stress-induced epigenetic modifications could therefore contribute to the increased CRH expression and the HPA axis dysfunction that is observed in rodents following chronic stress in adulthood (Zhu et al 2014) and in human stress-related pathology (Tsigos & Chrousos 2002). In contrast, both acute and chronic stress have been found to reduce BDNF expression in the mouse and rat hippocampus, which was associated with increased local H3K27 methylation (Tsankova et al 2006), decreased H3 acetylation (Fuchikami et al 2009), and enhanced Bdnf promoter methylation (Roth et al 2011, Niknazar et al 2016. Furthermore, hippocampal expression levels of TrkB were reduced following forced swim stress, which increased methylation of Trkb (Niknazar et al 2016).…”

“…In contrast, both acute and chronic stress have been found to reduce BDNF expression in the mouse and rat hippocampus, which was associated with increased local H3K27 methylation (Tsankova et al 2006), decreased H3 acetylation (Fuchikami et al 2009), and enhanced Bdnf promoter methylation (Roth et al 2011, Niknazar et al 2016. Furthermore, hippocampal expression levels of TrkB were reduced following forced swim stress, which increased methylation of Trkb (Niknazar et al 2016). Decreased hippocampal BDNF has been hypothesized to underlie hippocampal dysfunction in response to traumatic stress (Johnsen & Asbjornsen 2008, Moore 2009), as BDNF is an important neurotrophic factor that enhances long-term potentiation and other forms of synaptic plasticity in the hippocampus (Korte et al 1996).…”

Decreased Plasma BDNF Levels of Patients with Somatization Disorder

“…BDNF is also involved in various other mental and physical conditions such as stress, 16 17 allergic disease 18 19 and pain. BDNF which serves as a pain modulator plays an important role in pain sensation.…”