Effects of single-dose antipurinergic therapy on behavioral and molecular alterations in the valproic acid-induced animal model of autism
| Autor: | Giovanna Carello-Collar, Júlio Santos-Terra, Mellanie Fontes-Dutra, Ana Regina Geciauskas Lage Castillo, Juliana Corrêa-Velloso, Henning Ulrich, Iohanna Deckmann, Yahaira Naaldijk, Gabriela Zanotto Staevie, Mauro Mozael Hirsch, Maria C. Gonçalves, Bruna Rabelo, Tomasz Schneider, Guilherme Bauer-Negrini, Victorio Bambini-Junior, Carmem Gottfried, Gustavo Brum Schwingel, Marília Körbes-Rockenbach |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Elevated plus maze Purinergic Antagonists Receptor expression Suramin Hippocampus Pharmacology 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Pregnancy mental disorders medicine Animals Autistic Disorder Valproic Acid business.industry Purinergic receptor Receptors Purinergic Brain Purinergic signalling medicine.disease COMPORTAMENTO ANIMAL Rats Disease Models Animal 030104 developmental biology Prenatal Exposure Delayed Effects Autism Anticonvulsants Female lipids (amino acids peptides and proteins) business 030217 neurology & neurosurgery Locomotion medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Neuropharmacology, 2020, Vol.167, pp.107930 [Peer Reviewed Journal] |
| ISSN: | 0028-3908 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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