Class I histone deacetylase inhibition ameliorates social cognition and cell adhesion molecule plasticity deficits in a rodent model of autism spectrum disorder

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Title: Class I histone deacetylase inhibition ameliorates social cognition and cell adhesion molecule plasticity deficits in a rodent model of autism spectrum disorder
Authors: Foley, Andrew G.
Gannon, Shane
Rombach-Mullan, Nanette
Prendergast, Alison
Barry, Claire
Cassidy, Andrew W.
Regan, Ciaran M.
Permanent link: http://hdl.handle.net/10197/3779
Date: Sep-2012
Abstract: In utero exposure of rodents to valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has been proposed to induce an adult phenotype with behavioural characteristics reminiscent of those observed in autism spectrum disorder (ASD). We have evaluated the face validity of this model in terms of social cognition deficits which are a major core symptom of ASD. We employed the social approach avoidance paradigm as a measure of social reciprocity, detection of biological motion that is crucial to social interactions, and spatial learning as an indicator of dorsal stream processing of social cognition and found each parameter to be significantly impaired in Wistar rats with prior in utero exposure to VPA. We found no significant change in the expression of neural cell adhesion molecule polysialylation state (NCAM PSA), a measure of construct validity, but a complete inability to increase its glycosylation state which is necessary to mount the neuroplastic response associated with effective spatial learning. Finally, in all cases, we found chronic HDAC inhibition, with either pan-specific or HDAC1-3 isoform-specific inhibitors, to significantly ameliorate deficits in both social cognition and its associated neuroplastic response. We conclude that in utero exposure to VPA provides a robust animal model for the social cognitive deficits of ASD and a potential screen for the development of novel therapeutics for this condition.
Funding Details: Not applicable
Type of material: Journal Article
Publisher: Elsevier
Copyright (published version): 2012 Elsevier Ltd.
Keywords: SAHA;NCAM PSA;MS-275;VPA;Histone deacetylase;Social interaction;Biological motion;Spatial learning;Synaptic plasticity
Subject LCSH: Valproic acid
Histone deacetylase
Autism spectrum disorder (ASD)
Hydroxamic acids
DOI: 10.1016/j.neuropharm.2012.05.042
Language: en
Status of Item: Peer reviewed
Appears in Collections:Biomolecular and Biomedical Science Research Collection

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