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

Author(s):Show less -

Hirsch, Mauro Mozael ^{[1, 2, 3]} ; Deckmann, Iohanna ^{[1, 2, 3]} ; Santos-Terra, Julio ^{[1, 2, 3]} ; Staevie, Gabriela Zanotto ^{[1, 2, 3]} ; Fontes-Dutra, Mellanie ^{[1, 2, 3]} ; Carello-Collar, Giovanna ^{[1, 2, 3]} ; Korbes-Rockenbach, Marilia ^{[1, 2, 3]} ; Schwingel, Gustavo Brum ^{[1, 2, 3]} ; Bauer-Negrini, Guilherme ^{[1, 2, 3]} ; Rabelo, Bruna ^{[1, 2, 3]} ; Bittencourt Goncalves, Maria Carolina ^[4] ; Correa-Velloso, Juliana ^[4] ; Naaldijk, Yahaira ^[4] ; Geciauskas Castillo, Ana Regina ^[4] ; Schneider, Tomasz ^[5] ; Bambini-Junior, Victorio ^{[6, 1, 3, 7]} ; Ulrich, Henning ^{[4, 7]} ; Gottfried, Carmem ^{[1, 2, 3, 7]}

Affiliation

^[1] Univ Fed Rio Grande do Sul, Translat Res Grp Autism Spectrum Disorders GETTEA, Rua Ramiro Barcelos 2600, BR-90035003 Porto Alegre, RS - Brazil

^[2] Univ Fed Rio Grande do Sul, Dept Biochem, Ramiro Barcelos St 2600, BR-90035003 Porto Alegre, RS - Brazil

^[3] Natl Inst Sci & Technol Neuroimmunomodulat INCT I, Ave Brasil 4365, BR-21045900 Rio De Janeiro, RJ - Brazil

^[4] Univ Sao Paulo, Inst Chem, Dept Biochem, Ave Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP - Brazil

^[5] Univ Durham, Sch Med Pharm & Hlth, Durham - England

^[6] Univ Cent Lancashire, Sch Pharm & Biomed Sci, Preston PR1 2HE, Lancs - England

^[7] Univ Cent Lancashire, Autism Wellbeing & Res Dev AWARD Inst, Preston PR1 2HE, Lancs - England

• Document type: Journal article
• Source: Neuropharmacology; v. 167, MAY 1 2020.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 12/50880-4 - Stem cells: from basic studies of kinin and purinergic receptor roles towards therapeutical applications
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/14343-2 - Dental pulp derived mesenchymal stem cells and its conditioned medium: a novel therapeutic approach for ALS
• Grantee: Yahaira Maria Naaldijk Palma
• Support Opportunities: Scholarships in Brazil - Post-Doctoral