☆ 4.5 Article

Region-specific alterations in glucocorticoid receptor expression in the postmortem brain of teenage suicide victims

PSYCHONEUROENDOCRINOLOGY (2013)

期刊

PSYCHONEUROENDOCRINOLOGY

卷 38, 期 11, 页码 2628-2639

出版社

PERGAMON-ELSEVIER SCIENCE LTD

DOI: 10.1016/j.psyneuen.2013.06.020

关键词

Glucocorticoid receptors; Mineralocorticoid receptors; HPA axis; GILZ; Prefrontal cortex; Hippocampus; Subiculum; Amygdala; Teenage suicide; Postmortem brain

类别

Endocrinology & Metabolism Neurosciences Psychiatry

资金

National Institute of Mental Health, Rockville, MD [RO1 MH 48153, RO1 MH 98554]

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Introduction: Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and suicide. The purpose of this study was to test the hypothesis that the reported dysregulation of the HPA axis in suicide may be related to a disturbed feedback inhibition caused by decreased corticoid receptors in the brain. We therefore determined the protein and gene expression of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the postmortem brain of teenage suicide victims and matched normal controls. Methods: Protein and mRNA expression of GR (GR-alpha and GR-beta) and MR and the mRNA expression of glucocorticoid-induced leucine zipper (GILZ), a target gene for GR were determined by immuno-labeling using Western blot technique and the real-time RT-polymerase chain reaction (qPCR) technique in the prefrontal cortex (PFC), hippocampus, subiculum, and amygdala obtained from 24 teenage suicide victims and 24 teenage control subjects. Results: We observed that protein and gene expression of GR-alpha was significantly decreased in the PFC and amygdala, but not in the hippocampus or subiculum, of teenage suicide victims compared with normal control subjects. Also, the mRNA levels of GR inducible target gene GILZ was significantly decreased in PFC and amygdaloid nuclei but not in hippocampus compared with controls. In contrast, no significant differences were observed in protein or gene expression of MR in any of the areas studied between teenage suicide victims and normal control subjects. There was no difference in the expression of GR-beta in the PFC between suicide victims and normal controls. Conclusions: These results suggested that the observed dysregulation of the HPA axis in suicide may be related to a decreased expression of GR-alpha and GR inducible genes in the PFC and amygdala of teenage suicide victims. The reason why GR receptors are not dysregulated in the hippocampus or subiculum, presumably two sites of stress action, are not clear at this time. (C) 2013 Elsevier Ltd. All rights reserved.

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The Neuroendocrine Impact of Acute Stress on Synaptic Plasticity

Raoni Conceicao dos-Santos, Brook L. W. Sweeten, Claire E. Stelly, Jeffrey G. Tasker

Summary: Stress has effects on the nervous system at different signaling levels and time scales. Glucocorticoids, the main effectors of stress plasticity, act on multiple receptor subtypes in different cellular compartments, leading to changes in synaptic transmission and neuronal excitability. This review focuses on the rapid actions of acute stress-induced glucocorticoids in modulating synaptic and intrinsic neuronal properties. The stress-related brain structures, such as the hypothalamus, hippocampus, amygdala, and prefrontal cortex, exhibit synaptic plasticity in response to single or short-term stress exposure.

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