Effects of single-dose antipurinergic therapy on behavioral and molecular alterations in the valproic acid-induced animal model of autism

Hirsch, Mauro Mozael and Deckmann, Iohanna and Santos-Terra, Júlio and Staevie, Gabriela Zanotto and Fontes-Dutra, Mellanie and Carello-Collar, Giovanna and Körbes-Rockenbach, Marília and Brum Schwingel, Gustavo and Bauer-Negrini, Guilherme and Rabelo, Bruna and Gonçalves, Maria Carolina Bittencourt and Corrêa-Velloso, Juliana and Naaldijk, Yahaira and Castillo, Ana Regina Geciauskas and Schneider, Tomasz and Bambini-Junior, Victorio and Ulrich, Henning and Gottfried, Carmem (2020) Effects of single-dose antipurinergic therapy on behavioral and molecular alterations in the valproic acid-induced animal model of autism. Neuropharmacology, 167. ISSN 0028-3908

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Abstract

Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, and stereotyped behavior. Environmental factors, such as prenatal exposure to valproic acid (VPA), may contribute to the increased risk of ASD. Since disturbed functioning of the purinergic signaling system has been associated with the onset of ASD and used as a potential therapeutic target for ASD in both clinical and preclinical studies, we analyzed the effects of suramin, a non-selective purinergic antagonist, on behavioral, molecular and immunological in an animal model of autism induced by prenatal exposure to VPA. Treatment with suramin (20 mg/kg, intraperitoneal) restored sociability in the three-chamber apparatus and decreased anxiety measured by elevated plus maze apparatus, but had no impact on decreased reciprocal social interactions or higher nociceptive threshold in VPA rats. Suramin treatment did not affect VPA-induced upregulation of P2X4 and P2Y2 receptor expression in the hippocampus, and P2X4 receptor expression in the medial prefrontal cortex, but normalized an increased level of interleukin 6 (IL-6). Our results suggest an important role of purinergic signaling modulation in behavioral, molecular, and immunological aberrations described in VPA model, and indicate that the purinergic signaling system might be a potential target for pharmacotherapy in preclinical studies of ASD.

Item Type:
Journal Article
Journal or Publication Title:
Neuropharmacology
Additional Information:
Copyright © 2020 Elsevier Ltd. All rights reserved.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/3000/3004
Subjects:
ID Code:
168514
Deposited By:
Deposited On:
28 Apr 2022 10:35
Refereed?:
Yes
Published?:
Published
Last Modified:
03 May 2022 04:27