Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid

Neuroimmunomodulation. 2018;25(5-6):285-299. doi: 10.1159/000492113. Epub 2018 Aug 29.

Abstract

Autism spectrum disorder (ASD) is a highly prevalent developmental disorder characterized by deficits in communication and social interaction and in stereotyped or repetitive behaviors. Besides the classical behavioral dyad, several comorbidities are frequently present in patients with ASD, such as anxiety, epilepsy, sleep disturbances, and gastrointestinal tract dysfunction. Although the etiology of ASD remains unclear, there is supporting evidence for the involvement of both genetic and environmental factors. Valproic acid (VPA) is an anticonvulsant and mood stabilizer that, when used during the gestational period, increases the risk of ASD in the offspring. The animal model of autism induced by prenatal exposure to VPA demonstrates important structural and behavioral features that can be observed in individuals with autism; it is thus an excellent tool for testing new drug targets and developing novel behavioral and drug therapies. In addition, immunological alterations during pregnancy could affect the developing embryo because immune molecules can pass through the placental barrier. In fact, exposure to pathogens during the pregnancy is a known risk factor for ASD, and maternal immune activation can lead to autistic-like features in animals. Interestingly, neuroimmune alterations are common in both autistic individuals and in animal models of ASD. We summarize here the important alterations in inflammatory markers, such as cytokines and chemokines, in patients with ASD and in the VPA animal model.

Keywords: Animal model; Autism spectrum disorder; Cytokines; Neuroimmune alterations; Valproic acid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autistic Disorder / chemically induced
  • Autistic Disorder / immunology*
  • Disease Models, Animal
  • Enzyme Inhibitors / toxicity
  • Female
  • Humans
  • Mice
  • Neuroimmunomodulation / immunology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Valproic Acid / toxicity

Substances

  • Enzyme Inhibitors
  • Valproic Acid