Prenatal Exposure to Valproate in Animals and Autism

  • Victorio Bambini-Junior
  • Diego Baronio
  • Janine MacKenzie
  • Geancarlo Zanatta
  • Rudimar dos Santos Riesgo
  • Carmem Gottfried

Abstract

Valproic acid, synthesized for the first time by Burton in 1882, is largely used as a seizure inhibitor and as treatment for bipolar disorder. The drug is a known teratogen and prenatal exposure during the first trimester of pregnancy has been associated with significantly increased risks of autism. The development of an animal model of autism with prenatal exposure to valproic acid was speculated as a research tool to examine the mechanism involved in the etiology and pathophysiology of autism spectrum disorders. Construct, face, and predictive validities are present in this model, ensuring its effectiveness as a trustworthy research tool. Neurochemical, morphological, and behavioral abnormalities, similar to those found in individuals with autism have been described in this model. These abnormalities include changes in the monoamine system, and decreased number of Purkinje cells and motor neurons. The teratogenic effect of valproic acid is most likely mediated by inhibition of histone deacetylase activity. In addition, there is consistent evidence indicating that the central nervous system may be affected by valproic acid at different levels, such as neurochemical, morphological and, thus, behavioral. The following chapter will describe the range of possible molecular targets of valproic acid and its use as a reliable translational tool to study autism spectrum disorders.

Keywords

Cage Glutathione Cysteine Serotonin Lysine 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Victorio Bambini-Junior
    • 1
  • Diego Baronio
    • 2
  • Janine MacKenzie
    • 3
  • Geancarlo Zanatta
    • 4
  • Rudimar dos Santos Riesgo
    • 5
  • Carmem Gottfried
    • 4
  1. 1.Departamento de BioquimicaUniversidade Federal do Rio Grande do sul, Instituto de Ciencias Basicas da SaudePorto AlegreBrazil
  2. 2.Programa de Pós-Graduação em Saúde da Criança e do AdolescenteUniversidade Federal do Rio Grande do Sul, Faculdade de MedicinaPorto AlegreBrazil
  3. 3.Department of PhsychologyUniversity of ManitobaBCCanada
  4. 4.Departamento de BioquimicaUniversidade Federal do Rio Grande do Sul, Instituto de Ciencias Basicas da SaudePorto AlegreBrazil
  5. 5.Unidade de NeuropediatriaHospital de Clínicas de Porto AlegrePorto AlegreBrazil

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