TY - JOUR

T1 - Animal model of autism induced by prenatal exposure to valproate

T2 - behavioral changes and liver parameters

AU - Bambini-Junior, Victorio

AU - Rodrigues, Leticia

AU - Behr, Guilherme Antônio

AU - Moreira, José Cláudio Fonseca

AU - Riesgo, Rudimar

AU - Gottfried, Carmem

N1 - Copyright © 2011. Published by Elsevier B.V.

PY - 2011/8/23

Y1 - 2011/8/23

N2 - 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.

AB - 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.

KW - Aging/psychology

KW - Alanine Transaminase/blood

KW - Animals

KW - Anticonvulsants

KW - Aspartate Aminotransferases/blood

KW - Autistic Disorder/chemically induced

KW - Behavior, Animal/drug effects

KW - Catalase/metabolism

KW - Disease Models, Animal

KW - Female

KW - Liver/metabolism

KW - Liver Function Tests

KW - Maze Learning/drug effects

KW - Oxidation-Reduction

KW - Oxidative Stress/drug effects

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects

KW - Protein Carbonylation

KW - Rats

KW - Rats, Wistar

KW - Social Behavior

KW - Sulfhydryl Compounds/metabolism

KW - Superoxide Dismutase/metabolism

KW - Thiobarbituric Acid Reactive Substances/metabolism

KW - Valproic Acid

U2 - 10.1016/j.brainres.2011.06.015

DO - 10.1016/j.brainres.2011.06.015

M3 - Journal article

C2 - 21767826

VL - 1408

SP - 8

EP - 16

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -