Central and peripheral alterations in the inflammatory response in a mouse model for autism

DEPINO A; LUCCHINA L; KAZLAUSKAS N; CAMPOLONGO M

Nueva Orleans

Congreso; Annual Meeting of the Society for Neuroscience 2012; 2012

Society for Neuroscience

Epidemiological, serological, and postmortem studies have shown an association between immune alterations and autism spectrum disorders (ASD). However, there is no direct clinical evidence on the effects of inflammatory processes in the etiology and/or pathophysiology of these disorders. Using environmental animal models of ASD, we aim to study the role of inflammatory processes in both the origin and the development of these pathologies. Here we will present our data characterizing the inflammatory response in the VPA mouse model of autism. Using either a F1 of inbred strains (C57BL/6J x Balb/c strains) and an outbred strain (CF1), we found that the maternal injection of VPA at gestational day 12.5 leads to reduced social behaviors in the adult offspring. This adds to previous evidence showing that the VPA model has good face validity. Using this drug with unknown inflammatory properties, we studied both the central and peripheral inflammatory responses in young and adult mice. Offspring of VPA-treated dams show astrogliosis both in the postnatal and adult brain. Moreover, microglia activation in observed in VPA-treated mice and augmented when they were challenged in adulthood with an inflammatory stimulus. VPA-injected mice show increased peripheral inflammatory responses upon stimulation, evidenced as augmented HPA-axis activation and increased cytokine expression in the spleen. Moreover, VPA-treated mice showed exacerbated pro-inflammatory cytokines response in different regions of the brain. Our results show an altered inflammatory response in a mouse model for autism and suggest that peripheral inflammatory events can contribute to the pathophysiology of ASD.