CONICET | Buscador de Institutos y Recursos Humanos

Autism spectrum disorders (ASD) are severe neurodevelopmental disorders with a prevalence estimated in 9.0 per 1000 population. The symptoms of autism involve significant impairments in social, communicative, and cognitive functioning. The exact underlying causes of autism are still unclear. Epidemiological, serological, and postmortem studies have associated brain inflammation with ASD. However, there is not evidence of a direct effect of neuroinflammation on the pathogenesis of ASD. Our working hypothesis is that the glial response represents an underlying common factor in the different proposed etiologies of ASD. The prenatal exposure to valproic acid (VPA) is associated with the development of ASD symptoms in humans. We validated a mouse model of ASD by treating pregnant mice with VPA at the gestational day 13. We studied the role of glial activation and brain cytokines in this model with the aim to understand their involvement in the development of ASD-related behaviors. Our results show that pups exposed prenatally to VPA experience a delay in the righting reflex, and they show reduced social interaction and increased anxiety-related behavior in adulthood. No differences in depression-related behaviors were observed. In adulthood, VPA-treated mice presented activated glial cells in the cortex and cerebellum. In addition, prenatal exposure to VPA led to an exacerbated response to an inflammatory stimulus in adulthood, observed as an increment in the expression of pro-inflammatory cytokines and as a bigger activation of the hypothalamus-pituitary-adrenal axis. These results show a basal and subclinical inflammatory state in the brains of VPA-exposed animals, a increased reactivity to adult inflammatory stimuli, and suggest that the neuroinflammation previously observed in postmortem studies represent an actual ASD phenotype.