Deficits in KCC2 and activation of the HPA axis lead to depressionlike behavior following social defeat

Stephanie Miller,Jamie Maguire

doi:10.7243/2052-8000-2-2

Abstract

Abstract Background: Chronic social stress triggers the development of major depression in humans and depression-like behavior in animal models. Hyperexcitability of the hypothalamic-pituitary-adrenal (HPA) axis has

Highlights

Major depressive disorder is one of the most prevalent mood disorders, affecting approximately 6.7% of the population at any one time [1] and up to 20% of the population at some point in their lives [2]
There was no significant difference in the CORT levels between dominant (29.41±4.96 ng/ml) and control mice (21.07±4.83 ng/ml) (Figure 2A), suggesting that HPA axis reactivity is only altered in submissive mice (n=8-10 mice per group; F(2,25)=3.39; p
To determine if this same regulatory mechanism plays a role in dysregulation of the HPA axis following chronic social defeat stress, we examined the total levels of K+/Cl- co-transporter 2 (KCC2) and the phosphorylation of KCC2 residue Ser940 in the paraventricular nucleus (PVN) of dominant and submissive mice using Western blot analysis

Summary

Introduction

Major depressive disorder is one of the most prevalent mood disorders, affecting approximately 6.7% of the population at any one time [1] and up to 20% of the population at some point in their lives [2]. Chronic social and psychological stress trigger the development of depression in both humans [2,8,9] and animal models [2,9,10,11]. The pathophysiological causes of depression are undoubtedly varied [2,18,19,20,21], it is clear that major depression is associated with stress and hyperactivity of the hypothalamicpituitary-adrenal (HPA) axis [2,22,23]. Dysregulation of the HPA axis precedes the development of depression and is implicated in mediating the effects of stress on depression-like behavior. Chronic social stress triggers the development of major depression in humans and depression-like behavior in animal models. The purpose of this study was to determine if chronic social defeat stress activates the HPA axis using similar mechanisms which may contribute to the development of depression-like behavior

Objectives

Methods

Results

Discussion

Conclusion