| Literature DB >> 23644483 |
Xiao-Dong Wang1, Yun-Ai Su, Klaus V Wagner, Charilaos Avrabos, Sebastian H Scharf, Jakob Hartmann, Miriam Wolf, Claudia Liebl, Claudia Kühne, Wolfgang Wurst, Florian Holsboer, Matthias Eder, Jan M Deussing, Marianne B Müller, Mathias V Schmidt.
Abstract
Stress impairs cognition via corticotropin-releasing hormone receptor 1 (CRHR1), but the molecular link between abnormal CRHR1 signaling and stress-induced cognitive impairments remains unclear. We investigated whether the cell adhesion molecule nectin-3 is required for the effects of CRHR1 on cognition and structural remodeling after early-life stress exposure. Postnatally stressed adult mice had decreased hippocampal nectin-3 levels, which could be attenuated by CRHR1 inactivation and mimicked by corticotropin-releasing hormone (CRH) overexpression in forebrain neurons. Acute stress dynamically reduced hippocampal nectin-3 levels, which involved CRH-CRHR1, but not glucocorticoid receptor, signaling. Suppression of hippocampal nectin-3 caused spatial memory deficits and dendritic spine loss, whereas enhancing hippocampal nectin-3 expression rescued the detrimental effects of early-life stress on memory and spine density in adulthood. Our findings suggest that hippocampal nectin-3 is necessary for the effects of stress on memory and structural plasticity and indicate that the CRH-CRHR1 system interacts with the nectin-afadin complex to mediate such effects.Entities:
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Year: 2013 PMID： 23644483 DOI： 10.1038/nn.3395
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884