title: Nectin-3 links CRHR1 signaling to stress-induced memory deficits and spine loss.
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.
authors: Max Planck Institute of Psychiatry, Munich, Germany.
authors: Xiao-Dong
authors: XD
authors: Wang
authors: Yun-Ai
authors: YA
authors: Su
authors: Klaus V
authors: KV
authors: Wagner
authors: Charilaos
authors: C
authors: Avrabos
authors: Sebastian H
authors: SH
authors: Scharf
authors: Jakob
authors: J
authors: Hartmann
authors: Miriam
authors: M
authors: Wolf
authors: Claudia
authors: C
authors: Liebl
authors: Claudia
authors: C
authors: Kühne
authors: Wolfgang
authors: W
authors: Wurst
authors: Florian
authors: F
authors: Holsboer
authors: Matthias
authors: M
authors: Eder
authors: Jan M
authors: JM
authors: Deussing
authors: Marianne B
authors: MB
authors: Müller
authors: Mathias V
authors: MV
authors: Schmidt
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D049229:Dendritic Spines / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D000075983:Nectins; D016548:Prosencephalon / Q000473:pathology / Q000502:physiology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics; D000099052:CRF Receptor, Type 1
chemical_list: D015815:Cell Adhesion Molecules; C000619017:Nectin3 protein, mouse; D000075983:Nectins; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
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