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- Title
Nectin-3 links CRHR1 signaling to stress-induced memory deficits and spine loss.
- Authors
Wang, Xiao-Dong; Su, Yun-Ai; Wagner, Klaus V; Avrabos, Charilaos; Scharf, Sebastian H; Hartmann, Jakob; Wolf, Miriam; Liebl, Claudia; Kühne, Claudia; Wurst, Wolfgang; Holsboer, Florian; Eder, Matthias; Deussing, Jan M; Müller, Marianne B; Schmidt, Mathias V
- 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.
- Subjects
CORTICOTROPIN releasing hormone receptors; MEMORY; SPINAL cord; NECTINS; PSYCHOLOGICAL stress; COGNITION
- Publication
Nature Neuroscience, 2013, Vol 16, Issue 6, p706
- ISSN
1097-6256
- Publication type
Article
- DOI
10.1038/nn.3395