title: Animal model of autism induced by prenatal exposure to valproate: behavioral changes and liver parameters.
abstract: Autism is characterized by behavioral impairments in three main domains: social interaction; language, communication and imaginative play; and range of interests and activities. This syndrome has attracted social attention by its high prevalence. The animal model induced by prenatal exposure to valproic acid (VPA) has been proposed to study autism. Several characteristics of behavioral abnormalities found in the VPA rats, such as repetitive/stereotypic-like activity and deficit in social interaction have been correlated with autism. Features like flexibility to change strategy, social memory and metabolic status of the induced rats have not been examined. Thus, the main aim of this work was to investigate additional behavioral rodent similarities with autism, as well as, liver redox parameters after prenatal exposure to VPA. Young rats from the VPA group presented aberrant approach to a stranger rat, decreased conditioned place preference to conspecifics, normal spatial learning and a lack of flexibility to change their strategy. As adults, they presented inappropriate social approach to a stranger rat, decreased preference for social novelty, apparently normal social recognition and no spatial learning deficits. Examination of the liver from the VPA group presented significantly increased (12%) levels of catalase (CAT) activity, no alteration in superoxide dismutase (SOD) activity and a decrease in the SOD/CAT ratio. TBARS, sulfhydril and carbonyl contents, and serum levels of aminotransferases remained unchanged. In summary, rats prenatally exposed to VPA presented decreased flexibility to change strategy and social impairments similar to the autism symptoms, contributing to the understanding of neurodevelopmental symptoms and oxidative imbalance associated to the autism spectrum disorder.
authors.affiliation: Federal University of Rio Grande do Sul, Research Group in Neuroglial Plasticity, Porto Alegre, RS, Brazil. victoriobambini@gmail.com
authors.forename: Victorio
authors.initials: V
authors.lastname: Bambini-Junior
authors.forename: Leticia
authors.initials: L
authors.lastname: Rodrigues
authors.forename: Guilherme Antônio
authors.initials: GA
authors.lastname: Behr
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
authors.forename: Rudimar
authors.initials: R
authors.lastname: Riesgo
authors.forename: Carmem
authors.initials: C
authors.lastname: Gottfried
mesh_terms: D000375:Aging / Q000523:psychology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000927:Anticonvulsants; D001219:Aspartate Aminotransferases / Q000097:blood; D001321:Autistic Disorder / Q000139:chemically induced* / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008099:Liver / Q000378:metabolism*; D008111:Liver Function Tests; D018782:Maze Learning / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D050050:Protein Carbonylation; D051381:Rats; D017208:Rats, Wistar; D012919:Social Behavior; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014635:Valproic Acid
chemical_list: D000927:Anticonvulsants; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D014635:Valproic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase