Downregulation of the GABAA receptor β2 subunit in a rat model of autism
DOI:
https://doi.org/10.31157/an.v1iInpress.645Keywords:
GABA, GABAA, Autism, Valproic acid, GARB2Abstract
Introduction: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain, and GABA type A receptor (GABAA) activation mediates fast inhibitory actions. Numerous studies have shown that individual with autism spectrum disorder (ASD) exhibit abnormalities in the expression of GABAA receptors in various brain areas. Additionally, animal models of ASD have suggested alterations in GABAergic neurotransmission and a dysregulation in the balance between inhibitory and excitatory systems. Objective: We investigated the immunolabeling of the GABAA receptor β2 subunit (GARB2) in the hippocampus, the amygdala, and thalamus of infant rats prenatally exposed to valproic acid (VPA) as an ASD model. Methods: Pregnant females were injected with VPA (600mg/Kg, i.p.) during the twelfth embryonic day; control rats were injected with saline. On the fourteen-postnatal-day, rats from both experimental groups were anesthetized, transcardially perfused with 0.9% NaCl and 4% paraformaldehyde, and sequential coronal brain sections (40μm thickness) were obtained. Immunohistochemistry was performed to detect GARB2 and the relative optical density (OD) of expression was analyzed. Results: Our data showed a statistically significant downregulation of GARB2 in the lateral amygdaloid nucleus, as well as in the ventral and lateral thalamic nuclei when compared to control rats. No statistically significant differences were detected in the hippocampus. Discussion: Our findings suggest that prenatal exposure to VPA reduces GARB2 expression in limbic brain regions involved in social-emotional behaviors, like previous reports in individuals with ASD. Conclusion These results support for the involvement of the GABAergic system in the pathogenesis of ASD.
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January 2014-December 2021 © Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez. Open access articles under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
