Analysis of Extracellular Nucleotide Metabolism in Adult Zebrafish After Embryological Exposure to Valproic Acid

• Published in: Molecular neurobiology Vol. 54; no. 5; pp. 3542 - 3553
• Main Authors: Zimmermann, Fernanda Francine, Gaspary, Karina Vidarte, Siebel, Anna Maria, Leite, Carlos Eduardo, Kist, Luiza Wilges, Bogo, Mauricio Reis, Bonan, Carla Denise
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.07.2017; Springer Nature B.V
• Subjects: 5'-Nucleotidase - genetics; 5'-Nucleotidase - metabolism; Acids; Adenosine; Adenosine deaminase; Adenosine Deaminase - genetics; Adenosine Deaminase - metabolism; Adenosine diphosphate; Aging - metabolism; AMP; Animals; Anxiety; ATP; Autism; Biomedical and Life Sciences; Biomedicine; Brain; Brain - enzymology; Catabolism; Cell Biology; Cell Membrane - drug effects; Cell Membrane - metabolism; Embryo, Nonmammalian - metabolism; Embryology; Exposure; Extracellular Space - metabolism; Fish; Gene Expression Regulation - drug effects; Hydrolysis; Hyperactivity; Metabolism; Neurobiology; Neurodevelopmental disorders; Neurology; Neurosciences; Nucleotides - metabolism; Polymerase chain reaction; Reverse transcription; Social behavior; Social interaction; Solubility; Valproic acid; Valproic Acid - pharmacology; Zebrafish - embryology; Zebrafish - genetics; Zebrafish - metabolism; Purinergic system; Autism; Zebrafish; Adenosine; Adenosine deaminase; Ectonucleotidases
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-016-9917-z

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.