title: Embryological exposure to valproic acid induces social interaction deficits in zebrafish (Danio rerio): A developmental behavior analysis.
abstract: Changes in social behavior are associated with brain disorders, including mood disorders, stress, schizophrenia, Alzheimer's disease, and autism spectrum disorders (ASD). Autism is a complex neurodevelopmental disorder characterized by deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Zebrafish is one of the most social vertebrates used as a model in biomedical research, contributing to an understanding of the mechanisms that underlie social behavior. Valproic acid (VPA) is used as an anti-epileptic drug and mood stabilizer; however, prenatal VPA exposure in humans has been associated with an increased incidence of autism and it can also affect fetal brain development. Therefore, we conducted a behavioral screening at different periods of zebrafish development at 6, 30, 70, and 120dpf (days postfertilization) after VPA exposure in the early development stage to investigate social behavior, locomotion, aggression, and anxiety. VPA (48μM) exposure during the first 48hpf (hours postfertilization) did not promote changes on survival, morphology, and hatching rate at 24hpf, 48hpf, and 72hpf. The behavioral patterns suggest that VPA exposure induces changes in locomotor activity and anxiety at different developmental periods in zebrafish. Furthermore, a social interaction deficit is present at 70dpf and 120dpf. VPA exposure did not affect aggression in the adult stage at 70dpf and 120dpf. This is the first study that demonstrated zebrafish exposed to VPA during the first 48h of development exhibit deficits in social interaction, anxiety, and hyperactivity at different developmental periods.
authors.affiliation: PUCRS, Faculdade de Biociências, Programa de Pós-Graduação em Biologia Celular e Molecular, Laboratório de Neuroquímica e Psicofarmacologia, Avenida Ipiranga, 6681, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Fernanda Francine
authors.initials: FF
authors.lastname: Zimmermann
authors.affiliation: PUCRS, Faculdade de Biociências, Programa de Pós-Graduação em Biologia Celular e Molecular, Laboratório de Neuroquímica e Psicofarmacologia, Avenida Ipiranga, 6681, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Karina Vidarte
authors.initials: KV
authors.lastname: Gaspary
authors.affiliation: PUCRS, Instituto de Toxicologia e Farmacologia, Porto Alegre CEP 90619-900, Brazil.
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Leite
authors.affiliation: Universidade Federal de Pelotas, Programa de Pós-Graduação em Bioquímica e Bioprospecção, Campus Universitário Capão do Leão, s/n°, 96010-900 Pelotas, RS, Brazil.
authors.forename: Giana
authors.initials: G
authors.lastname: De Paula Cognato
authors.affiliation: PUCRS, Faculdade de Biociências, Programa de Pós-Graduação em Biologia Celular e Molecular, Laboratório de Neuroquímica e Psicofarmacologia, Avenida Ipiranga, 6681, 90619-900 Porto Alegre, RS, Brazil. Electronic address: cbonan@pucrs.br.
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
mesh_terms: D000374:Aggression / Q000187:drug effects; D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects*; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D007398:Interpersonal Relations; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D014635:Valproic Acid / Q000032:analysis / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D014635:Valproic Acid
keywords: Anxiety; Autism; Locomotion; Social interaction; Valproic acid; Zebrafish