ADVERSE EXPERIENCE DURING EARLY LIFE AND ADULTHOOD INTERACT TO ELEVATE tph2 mRNA EXPRESSION IN SEROTONERGIC NEURONS WITHIN THE DORSAL RAPHE NUCLEUS

被引：70

作者：

Gardner, K. L. ^{[2
]}

Hale, M. W. ^{[1
]}

Oldfield, S. ^{[2
]}

Lightman, S. L. ^{[2
]}

Plotsky, P. M. ^{[3
]}

Lowry, C. A. ^{[1
,2
]}

机构：

[1] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA

[2] Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Bristol, Avon, England

[3] Emory Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA

来源：

NEUROSCIENCE | 2009年 / 163卷 / 04期

基金：

英国生物技术与生命科学研究理事会;

关键词：

anxiety; depression; maternal separation; serotonin; stress; tryptophan hydroxylase; C-FOS EXPRESSION; TRYPTOPHAN-HYDROXYLASE; MAJOR DEPRESSION; STRESSOR CONTROLLABILITY; IMMOBILIZATION STRESS; MATERNAL SEPARATION; GENE-EXPRESSION; ANIMAL-MODELS; BRAIN-REGIONS; SOCIAL STRESS;

D O I：

10.1016/j.neuroscience.2009.07.055

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Anxiety disorders, depression and animal models of vulnerability to a depression-like syndrome have been associated with dysregulation of brain serotonergic systems. These effects could result from genetic influences, adverse early life experiences (ELE), or acute stressful life events, all of which can alter serotonergic neurotransmission and have been implicated in determining vulnerability to neuropsychiatric disorders. To evaluate the effects of ELE, adverse experiences during adulthood, and potential interactions between these factors on neuronal tryptophan hydroxylase 2 (tph2) mRNA expression, we investigated in rats the effects of maternal separation (MS)(separation from the dam for 180 min/day from postnatal day 2-14; MS180, a model of vulnerability to a depression-like syndrome), neonatal handling (separation from the dam for 15 min/day from postnatal day 2-14; MS15, a model of decreased stress sensitivity), or normal animal facility rearing (AFR) control conditions, with or without subsequent exposure to adult social defeat, on tph2 mRNA expression in the dorsal raphe nucleus (DR). Among rats exposed to social defeat, MS180 rats had increased tph2 mRNA expression in the DR, while MS15 rats had decreased tph2 mRNA expression compared to AFR rats. Social defeat increased tph2 mRNA expression, but only in MS180 rats and only in the "lateral wings" of the DR, a subdivision of the DR that is part of a sympathomotor command center. Overall, these data demonstrate that ELE and stressful experience during adulthood interact to determine tph2 mRNA expression. These changes in tph2 mRNA expression represent a potential mechanism through which adverse ELEs and stressful life experiences during adulthood may interact to increase vulnerability to stress-related psychiatric disease. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：991 / 1001

页数：11

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