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          Institute: MPI für Psychiatrie     Collection: Publikationen MPI für Psychiatrie     Display Documents

ID: 563788.0, MPI für Psychiatrie / Publikationen MPI für Psychiatrie
Forebrain CRHR1 deficiency attenuates chronic stress-induced cognitive deficits and dendritic remodeling
Authors:Wang, X. D.; Chen, Y. C.; Wolf, M.; Wagner, K. V.; Liebl, C.; Scharf, S. H.; Harbich, D.; Mayer, B.; Wurst, W.; Holsboer, F.; Deussing, J. M.; Baram, T. Z.; Müller, M. B.; Schmidt, M. V.
Date of Publication (YYYY-MM-DD):2011-06
Title of Journal:Neurobiology of Disease
Issue / Number:3
Start Page:300
End Page:310
Review Status:not specified
Audience:Not Specified
Abstract / Description:Chronic stress evokes profound structural and molecular changes in the hippocampus, which may underlie spatial memory deficits. Corticotropin-releasing hormone (CRH) and CRH receptor 1 (CRHR1) mediate some of the rapid effects of stress on dendritic spine morphology and modulate learning and memory, thus providing a potential molecular basis for impaired synaptic plasticity and spatial memory by repeated stress exposure. Using adult male mice with CRHR1 conditionally inactivated in the forebrain regions, we investigated the role of CRH-CRHR1 signaling in the effects of chronic social defeat stress on spatial memory, the dendritic morphology of hippocampal CA3 pyramidal neurons, and the hippocampal expression of nectin-3, a synaptic cell adhesion molecule important in synaptic remodeling. In chronically stressed wild-type mice, spatial memory was disrupted, and the complexity of apical dendrites of CA3 neurons reduced. In contrast, stressed mice with forebrain CRHR1 deficiency exhibited normal dendritic morphology of CA3 neurons and mild impairments in spatial memory. Additionally, we showed that the expression of nectin-3 in the CA3 area was regulated by chronic stress in a CRHR1-dependent fashion and associated with spatial memory and dendritic complexity. Moreover, forebrain CRHR1 deficiency prevented the down-regulation of hippocampal glucocorticoid receptor expression by chronic stress but induced increased body weight gain during persistent stress exposure. These findings underscore the important role of forebrain CRH-CRHR1 signaling in modulating chronic stress-induced cognitive, structural and molecular adaptations, with implications for stress-related psychiatric disorders. (c) 2011 Elsevier Inc. All rights reserved.
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für Psychiatrie
Identifiers:ISI:000290081700010 [ID No:1]
ISSN:0969-9961 [ID No:2]
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