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Wang, X.D.* ; Chen, Y.* ; 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.*

Forebrain CRHR1 deficiency attenuates chronic stress-induced cognitive deficits and dendritic remodeling.

Neurobiol. Dis. 42, 300-310 (2011)
DOI PMC
Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chronic stress; Cognition; CRHR1; Dendrite; Hippocampus; Nectin-3
Sprache englisch
Veröffentlichungsjahr 2011
HGF-Berichtsjahr 2011
ISSN (print) / ISBN 0969-9961
e-ISSN 1095-953X
Zeitschrift Neurobiology of Disease
Quellenangaben Band: 42, Heft: 3, Seiten: 300-310 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Oxford, UK
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30204 - Cell Programming and Repair
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-520600-001
G-500500-001
G-500500-003
PubMed ID 21296667
DOI 10.1016/j.nbd.2011.01.020
Scopus ID 79954630809
Erfassungsdatum 2011-09-15
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