Animal Model of Autism Induced by Prenatal Exposure to Valproate: Behavioral Changes and Liver Parameters

Thursday, May 17, 2012
Sheraton Hall (Sheraton Centre Toronto)
9:00 AM
G. Mueller de Melo1, V. Bambini-Junior1, L. Rodrigues2, G. Behr1, M. S. Michels1, M. Dutra1, G. D. Nunes1, G. Zanatta1, R. Riesgo3 and C. Gottfried1, (1)Department of Biochemistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil, (2)Department of Neurochemistry, University of São Paulo (USP), São Paulo, Brazil, (3)Universidade Federal do Rio Grande do Sul - Brasil, Porto Alegre, RS, Brazil
Background: Even though twin studies show a strong genetic component in ASD and multiple interacting genetic factors as the main causative determinants of autism the etiology remains unknown. However, in addition to the genetic predisposition, epidemiological studies indicate that it is necessary for these genetic factors to interact with exposure to environmental factors e.g. prenatal exposure to xenobiotics, such as thalidomide and valproic acid (VPA). Based on these evidence, a rodent model to study autism was proposed. The single injection of VPA on the pregnant rat lead to an offspring with several altered behaviors.

Objectives: 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.

Methods: The behavioral tests we performed in young rats were sociability tests in a three chambered apparatus (one phase) and Y-maze; and in adult rats were sociability tests in a three chambered apparatus (two phases) and Morris Water Maze. Liver cytotoxicity was investigated by the serum activity of the hepatic enzyme markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Moreover, the activity of two important antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) and oxidative damage, by damage on lipids (TBARS), damage on proteins (−SH and carbonyl content) had also been quantified in liver samples.

Results: 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 CAT activity, no alteration in SOD activity and a decrease in the SOD/CAT ratio. TBARS, sulfhydril and carbonyl contents, and serum levels of aminotransferases remained unchanged.

Conclusions: 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 alterations and oxidative imbalance associated to the ASD.

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