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Nectin-3 links CRHR1 signaling to stress-induced memory deficits and spine loss.
|Title||Nectin-3 links CRHR1 signaling to stress-induced memory deficits and spine loss.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Wang 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|
|Date Published||2013 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 Journal||Nat. Neurosci.|