Rapid loss of dendritic spines after stress involves derangement of spine dynamics by corticotropin-releasing hormone.
Chronic stress causes dendritic regression and loss of dendritic spines in hippocampal neurons that is accompanied by deficits in synaptic plasticity and memory. However, the responsible mechanisms remain unresolved. Here, we found that within hours of the onset of stress, the density of dendritic spines declined in vulnerable dendritic domains. This rapid, stress-induced spine loss was abolished by blocking the receptor (CRFR(1)) of corticotropin-releasing hormone (CRH), a hippocampal neuropeptide released during stress. Exposure to CRH provoked spine loss and dendritic regression in hippocampal organotypic cultures, and selective blockade of the CRFR(1) receptor had the opposite effect. Live, time-lapse imaging revealed that CRH reduced spine density by altering dendritic spine dynamics: the peptide selectively and reversibly accelerated spine retraction, and this mechanism involved destabilization of spine F-actin. In addition, mice lacking the CRFR(1) receptor had augmented spine density. These findings support a mechanistic role for CRH-CRFR(1) signaling in stress-evoked spine loss and dendritic remodeling.
Chen
Yuncai
Y
Departments of Pediatrics and Anatomy/Neurobiology, University of California Irvine, Irvine, California 92697-4475, USA.
Dubé
Céline M
CM
Rice
Courtney J
CJ
Baram
Tallie Z
TZ
D000818:Animals; D002452:Cell Count / Q000379:methods; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone