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

Wang, X. D., Chen, Y. C., Wolf, M., Wagner, K. V., Liebl, C., Scharf, S. H., et al. (2011). Forebrain CRHR1 deficiency attenuates chronic stress-induced cognitive deficits and dendritic remodeling. Neurobiology of Disease, 42(3), 300-310.

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Wang, X. D.1, Autor           
Chen, Y. C., Autor
Wolf, M., Autor
Wagner, K. V.1, Autor           
Liebl, C., Autor
Scharf, S. H.2, Autor           
Harbich, D.2, Autor           
Mayer, B., Autor
Wurst, W.3, Autor           
Holsboer, F.4, Autor           
Deussing, J. M.5, Autor           
Baram, T. Z., Autor
Müller, M. B.2, Autor           
Schmidt, M. V.6, Autor           
Affiliations:
1AG Schmidt, Mathias, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society, ou_1607156              
2AG Müller, Marianne, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society, ou_1607153              
3Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              
4Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society, ou_1607139              
5AG Deussing, Jan, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society, ou_1607145              
6External Organizations, ou_persistent22              

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 Zusammenfassung: 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.

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Sprache(n): eng - English
 Datum: 2011-06
 Publikationsstatus: Erschienen
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 Art der Begutachtung: -
 Identifikatoren: eDoc: 563788
ISI: 000290081700010
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Titel: Neurobiology of Disease
Genre der Quelle: Zeitschrift
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Seiten: - Band / Heft: 42 (3) Artikelnummer: - Start- / Endseite: 300 - 310 Identifikator: ISSN: 0969-9961