Corticotropin-releasing factor and urocortin regulate spine and synapse formation: structural basis for stress-induced neuronal remodeling and pathology

N V Gounko, J D Swinny, D Kalicharan, S Jafari, N Corteen, M Seifi, R Bakels, J J L van der Want

Research output: Contribution to journalArticle

Abstract

Dendritic spines are important sites of excitatory neurotransmission in the brain with their function determined by their structure and molecular content. Alterations in spine number, morphology and receptor content are a hallmark of many psychiatric disorders, most notably those because of stress. We investigated the role of corticotropin-releasing factor (CRF) stress peptides on the plasticity of spines in the cerebellum, a structure implicated in a host of mental illnesses, particularly of a developmental origin. We used organotypic slice cultures of the cerebellum and restraint stress in behaving animals to determine whether CRF in vitro and stress in vivo affects Purkinje cell (PC) spine density. Application of CRF and urocortin (UCN) to cerebellar slice cultures increased the density of spines on PC signaling via CRF receptors (CRF-Rs) 1 and 2 and RhoA downregulation, although the structural phenotypes of the induced spines varied, suggesting that CRF-Rs differentially induce the outgrowth of functionally distinct populations of spines. Furthermore, CRF and UCN exert a trophic effect on the surface contact between synaptic elements by increasing active zones and postsynaptic densities and facilitating the alignment of pre- and post-synaptic membranes of synapses on PCs. In addition, 1 h of restraint stress significantly increased PC spine density compared with those animals that were only handled. This study provides unprecedented resolution of CRF pathways that regulate the structural machinery essential for synaptic transmission and provides a basis for understanding stress-induced mental illnesses.

Original languageEnglish
Pages (from-to)86-92
Number of pages7
JournalMolecular Psychiatry
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 2013

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Urocortins
Neuronal Plasticity
Corticotropin-Releasing Hormone
Synapses
Spine
Pathology
Purkinje Cells
Synaptic Transmission
Cerebellum
Cell Count
Post-Synaptic Density
Synaptic Membranes
Dendritic Spines
Molecular Structure
Psychiatry
Down-Regulation
Phenotype
Peptides
Brain

Cite this

Gounko, N V ; Swinny, J D ; Kalicharan, D ; Jafari, S ; Corteen, N ; Seifi, M ; Bakels, R ; van der Want, J J L. / Corticotropin-releasing factor and urocortin regulate spine and synapse formation: structural basis for stress-induced neuronal remodeling and pathology. In: Molecular Psychiatry. 2013 ; Vol. 18, No. 1. pp. 86-92.
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Corticotropin-releasing factor and urocortin regulate spine and synapse formation: structural basis for stress-induced neuronal remodeling and pathology. / Gounko, N V; Swinny, J D; Kalicharan, D; Jafari, S; Corteen, N; Seifi, M; Bakels, R; van der Want, J J L.

In: Molecular Psychiatry, Vol. 18, No. 1, 01.2013, p. 86-92.

Research output: Contribution to journalArticle

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