Neuroimmune alterations in autism: a translational analysis focusing on the animal model of autism induced by prenatal exposure to valproic acid

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 dysfunctions. 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 by prenatal exposure to VPA shows construct and face validity, since several changes seen in subjects with autism are also observed in the VPA animal model. Neuroimmune alterations are common both in autistic individuals and in animal models of autism. In addition, 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. Thus, immunological alterations in pregnancy could affect the developing embryo, since immune molecules can pass through the placental barrier. Here, we summarize important alterations in inflammatory markers, such cytokines and chemokines in patients with ASD and in the VPA animal model.