RT Journal Article
SR Electronic
T1 Rapid Loss of Dendritic Spines after Stress Involves Derangement of Spine Dynamics by Corticotropin-Releasing Hormone
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2903
OP 2911
DO 10.1523/JNEUROSCI.0225-08.2008
VO 28
IS 11
A1 Yuncai Chen
A1 Céline M. Dubé
A1 Courtney J. Rice
A1 Tallie Z. Baram
YR 2008
UL http://www.jneurosci.org/content/28/11/2903.abstract
AB 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 (CRFR1) 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 CRFR1 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 CRFR1 receptor had augmented spine density. These findings support a mechanistic role for CRH–CRFR1 signaling in stress-evoked spine loss and dendritic remodeling.