GABAρ3 expression in lobule X of the cerebellum is reduced in the valproate model of autism.

Abstract:

:Autism spectrum disorder (ASD) is a group of developmental disorders characterized by social interaction deficits, communication impairments, and stereotyped and repetitive behaviors. Additionally, impairments in the GABAergic circuitry have been associated with ASD. Several studies have shown that dysfunction of the cerebellum is a hallmark of ASD, and postmortem studies in humans reported a reduced density of Purkinje cells (PCs) together with an abnormal expression of GABAA subunits, among which GABAρ3 is expressed in early postnatal development, forms homomeric receptors with high affinity to the agonist (GABA EC50 ∼ 3 μM) and desensitize very little upon activation. Thus, we tested if the expression of GABAρ3 was modified by prenatal exposure to valproate (VPA), a well-known murine model of autism. The latency to find the nest increased in VPA-treated mice when compared to controls at postnatal day 8 (P8). Immunofluorescence studies showed a reduced expression of GABAρ3 in Purkinje cells (PCs) and ependymal glial cells (EGCs) from lobule X of VPA-treated mice. Finally, the expression of GABAρ3 increases linearly throughout normal development of the cerebellum, but this pattern is disrupted in the VPA model of autism. We conclude that the expression of GABAρ3 is reduced in PCs and EGCs from lobule X of the cerebellum in the VPA model of autism. Thus, GABAρ3 may be a relevant marker for ASD etiology.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Varman DR,Soria-Ortíz MB,Martínez-Torres A,Reyes-Haro D

doi

10.1016/j.neulet.2018.09.042

subject

Has Abstract

pub_date

2018-11-20 00:00:00

pages

158-163

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(18)30646-3

journal_volume

687

pub_type

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