An Advanced Transcriptional Response to Corticosterone After Single Prolonged Stress in Male Rats.

Jinlan Ding,Fang Han,Onno C Meijer,Xinzhao Chen

doi:10.3389/fnbeh.2021.756903

Abstract

Stress-related neuropsychiatric disorders are often accompanied by dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. In patients suffering from post-traumatic stress disorder (PTSD), increased sensitivity of glucocorticoid negative feedback has regularly been observed. The single prolonged stress (SPS) paradigm was developed to model increased negative feedback and other aspects of PTSD in rats. In this study, we used a setup that precluded the evaluation of negative feedback but rather served to test the hypothesis of the enhanced glucocorticoid receptor (GR) signaling in higher brain areas. We injected corticosterone or vehicle 7 days after SPS and evaluated plasma corticosterone, as well as gene expression in the dorsal hippocampus and amygdala. We observed a strikingly rapid change in the expression of established GR target genes (t = 30 min) only in the SPS group on exogenous corticosterone injection. Our results extend the notion of increased GR sensitivity in PTSD to include transcriptional responses in the hippocampus.

Highlights

In physiological conditions, glucocorticoid hormone levels increase systemically in response to stress, as a consequence of the activation of the hypothalamic-pituitary-adrenal (HPA) axis (Heim and Nemeroff, 2001; Smith and Vale, 2006; Jacobson, 2014; Boero et al, 2018)
We have only shown the data of the second experiment
The water intake of the single prolonged stress (SPS) group was significantly reduced compared to the control group (t = 2.416, p < 0.05, Figure 2B)

Summary

Introduction

Glucocorticoid hormone levels increase systemically in response to stress, as a consequence of the activation of the hypothalamic-pituitary-adrenal (HPA) axis (Heim and Nemeroff, 2001; Smith and Vale, 2006; Jacobson, 2014; Boero et al, 2018). Stress-related neuropsychiatric disorders are often accompanied by the dysfunction of the HPA axis. Patients suffering from post-traumatic stress disorder (PTSD) show alterations of the HPA system (Ströhle et al, 2008). The general consensus is that these patients exhibit increased sensitivity of glucocorticoid negative feedback (Kanter et al, 2001), based on, for example, the dexamethasone suppression test and the metyrapone stimulation test (Yehuda, 2005; Yehuda et al, 2009; Daskalakis et al, 2013).

Methods

Results

Conclusion