title: Analysis of Extracellular Nucleotide Metabolism in Adult Zebrafish After Embryological Exposure to Valproic Acid.
abstract: Autism is a neurodevelopmental disorder characterized by symptoms related to stereotyped movements, deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Evidence indicates an important role of extracellular ATP and adenosine as signaling molecules in autism. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering zebrafish is an animal model that may contribute towards to understanding the mechanisms that underlie social behavior, we investigated the purinergic signaling in a model of embryological exposure to valproic acid (VPA) that induces social interaction deficit in adult zebrafish. We demonstrated embryological exposure to VPA did not change ATP and ADP hydrolysis in zebrafish at 120 dpf, and the cytosolic (soluble) ADA activity was not altered. However, we observed an increase of AMP hydrolysis (12.5 %) whereas the ecto-ADA activity was decreased (19.2 %) in adult zebrafish submitted to embryological exposure to VPA. Quantitative reverse transcription PCR (RT-PCR) analysis showed changes on ntpd8, ADA 2.1, and A2a1 mRNA transcript levels. Brain ATP metabolism showed a rapid catabolism of ATP and ADP, whereas the extracellular metabolism of AMP and adenosine (ADO) occurred slowly. We demonstrated that embryological exposure to VPA altered biochemical and molecular parameters related to purinergic system in adult zebrafish. These findings indicate that the enzyme activities involved in the control of ATP and adenosine levels may be involved in the pathophysiological mechanisms of diseases related to the impairment of social interaction, such as autism.
authors.affiliation: Faculdade de Biociências, Programa de Pós-Graduação em Biologia Celular e Molecular, Laboratório de Neuroquímica e Psicofarmacologia, PUCRS, Avenida Ipiranga, 6681, 90619-900, Porto Alegre, RS, Brazil.
authors.forename: Fernanda Francine
authors.initials: FF
authors.lastname: Zimmermann
authors.affiliation: Faculdade de Biociências, Programa de Pós-Graduação em Biologia Celular e Molecular, Laboratório de Neuroquímica e Psicofarmacologia, PUCRS, Avenida Ipiranga, 6681, 90619-900, Porto Alegre, RS, Brazil.
authors.forename: Karina Vidarte
authors.initials: KV
authors.lastname: Gaspary
authors.affiliation: Programa de Pós-Graduação em Ciências Ambientais, Universidade Comunitária da Região de Chapecó, Avenida Senador Attílio Fontana, 591E, 89809-000, Chapecó, SC, Brazil.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Siebel
authors.affiliation: Instituto de Toxicologia e Farmacologia, PUCRS, Avenida Ipiranga, 6681, Porto Alegre, CEP 90619-900, Brazil.
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Leite
authors.affiliation: Faculdade de Biociências, Programa de Pós-Graduação em Biologia Celular e Molecular, Laboratório de Biologia Celular e Molecular, PUCRS, Avenida Ipiranga, 6681, 90619-900, Porto Alegre, RS, Brazil.
authors.forename: Luiza Wilges
authors.initials: LW
authors.lastname: Kist
authors.affiliation: Faculdade de Biociências, Programa de Pós-Graduação em Biologia Celular e Molecular, Laboratório de Biologia Celular e Molecular, PUCRS, Avenida Ipiranga, 6681, 90619-900, Porto Alegre, RS, Brazil.
authors.forename: Mauricio Reis
authors.initials: MR
authors.lastname: Bogo
authors.affiliation: Faculdade de Biociências, Programa de Pós-Graduação em Biologia Celular e Molecular, Laboratório de Neuroquímica e Psicofarmacologia, PUCRS, Avenida Ipiranga, 6681, 90619-900, Porto Alegre, RS, Brazil. cbonan@pucrs.br.
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism; D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006868:Hydrolysis; D009711:Nucleotides / Q000378:metabolism*; D012995:Solubility; D014635:Valproic Acid / Q000494:pharmacology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
chemical_list: D009711:Nucleotides; D014635:Valproic Acid; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase
keywords: Adenosine; Adenosine deaminase; Autism; Ectonucleotidases; Purinergic system; Zebrafish