TY - JOUR

T1 - Effects of single-dose antipurinergic therapy on behavioral and molecular alterations in the valproic acid-induced animal model of autism

AU - Hirsch, Mauro Mozael

AU - Deckmann, Iohanna

AU - Santos-Terra, Júlio

AU - Staevie, Gabriela Zanotto

AU - Fontes-Dutra, Mellanie

AU - Carello-Collar, Giovanna

AU - Körbes-Rockenbach, Marília

AU - Brum Schwingel, Gustavo

AU - Bauer-Negrini, Guilherme

AU - Rabelo, Bruna

AU - Gonçalves, Maria Carolina Bittencourt

AU - Corrêa-Velloso, Juliana

AU - Naaldijk, Yahaira

AU - Castillo, Ana Regina Geciauskas

AU - Schneider, Tomasz

AU - Bambini-Junior, Victorio

AU - Ulrich, Henning

AU - Gottfried, Carmem

N1 - Copyright © 2020 Elsevier Ltd. All rights reserved.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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.

KW - Animals

KW - Anticonvulsants/toxicity

KW - Autistic Disorder/chemically induced

KW - Brain/drug effects

KW - Disease Models, Animal

KW - Female

KW - Locomotion/drug effects

KW - Male

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects/chemically induced

KW - Purinergic Antagonists/administration & dosage

KW - Rats

KW - Receptors, Purinergic/metabolism

KW - Suramin/administration & dosage

KW - Valproic Acid/toxicity

U2 - 10.1016/j.neuropharm.2019.107930

DO - 10.1016/j.neuropharm.2019.107930

M3 - Journal article

C2 - 31904357

VL - 167

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

M1 - 107930

ER -