Modifications of glucocorticoid receptors mRNA expression in the hypothalamic-pituitary-adrenal axis in response to early-life stress in female Japanese quail.

C Zimmer,K A Spencer

doi:10.1111/jne.12228

Abstract

Stress exposure during early-life development can programme individual brain and physiology. The hypothalamic-pituitary-adrenal (HPA) axis is one of the primary targets of this programming, which is generally associated with a hyperactive HPA axis, indicative of a reduced negative-feedback. This reduced feedback efficiency usually results from a reduced level of the glucocorticoid receptor (GR) and/or the mineralocorticoid receptor (MR) within the HPA axis. However, a few studies have shown that early-life stress exposure results in an attenuated physiological stress response, suggesting an enhance feedback efficiency. In the present study, we aimed to determine whether early-life stress had long-term consequences on GR and MR levels in quail and whether the effects on the physiological response to acute stress observed in prenatally stressed individuals were underpinned by changes in GR and/or MR levels in one or more HPA axis components. We determined GR and MR mRNA expression in the hippocampus, hypothalamus and pituitary gland in quail exposed to elevated corticosterone during prenatal development, postnatal development, or both, and in control individuals exposed to none of the stressors. We showed that prenatal stress increased the GR:MR ratio in the hippocampus, GR and MR expression in the hypothalamus and GR expression in the pituitary gland. Postnatal stress resulted in a reduced MR expression in the hippocampus. Both early-life treatments permanently affected the expression of both receptor types in HPA axis regions. The effects of prenatal stress are in accordance with a more efficient negative-feedback within the HPA axis and thus can explain the attenuated stress response observed in these birds. Therefore, these changes in receptor density or number as a consequence of early-life stress exposure might be the mechanism that allows an adaptive response to later-life stressful conditions.

Highlights

Stress exposure during early life has long lasting impacts on both the structure and function of several tissues associated with a higher risk of developing health pathologies and behavioural disorders [1,2,3,4]
We hypothesised that the glucocorticoid receptor (GR):mineralocorticoid receptor (MR) ratio should be reduced in the hippocampus of quail exposed to prenatal stress
GR and MR mRNA expression in the different HPA axis regions. The expression of both receptors (MR and GR) was different between the three HPA axis regions (v2 = 15.80, d.f. = 1,189, P = 0.0004) (Fig. 1), with higher expression in the pituitary gland compared to both other tissues (Z> 3.39, P < 0.002)

Summary

Introduction

Stress exposure during early life has long lasting impacts on both the structure and function of several tissues associated with a higher risk of developing health pathologies and behavioural disorders [1,2,3,4]. The increase in glucocorticoid levels facilitates a switch of physiological processes and behaviours from non-essential activities to those that promote short-term survival, such as increased locomotion and mobilisation of energy stores This response is tightly regulated by a negative-feedback loop at the level of the hippocampus, hypothalamus and anterior pituitary to shut the HPA axis down and to return to a homeostatic point, avoiding the negative consequences of chronically elevated glucocorticoids [3,9]. A few studies have shown that early-life stress exposure can result in an attenuated physiological stress response later in life, suggesting enhanced negative-feedback efficiency [23,24,25,26] This programming of the HPA axis has been ascribed to modifications of GR and/or MR expression in the hippocampus and other feedback sites [1,2,3,18]. We hypothesised that the GR:MR ratio should be reduced in the hippocampus of quail exposed to prenatal stress

Objectives

Methods

Results