Nectin-3 links CRHR1 signaling to stress-induced memory deficits and spine loss.

TitleNectin-3 links CRHR1 signaling to stress-induced memory deficits and spine loss.
Publication TypeJournal Article
Year of Publication2013
AuthorsWang X-D, Su Y-A, Wagner KV, Avrabos C, Scharf SH, Hartmann J, Wolf M, Liebl C, Kühne C, Wurst W, Holsboer F, Eder M, Deussing JM, Müller MB, Schmidt MV
JournalNature neuroscience
Date Published2013 Jun

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.

Alternate JournalNat. Neurosci.