Alterations in the inflammatory response in a mouse model of autism

LUCCHINA L; DEPINO AM

Huerta Grande, Córdoba, Argentina

Encuentro; II Reunión Conjunta de Neurociencias; 2010

Sociedad Argentina de Neurociencias - Taller de Neurociencias

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder characterized by significant impairments in social, communicative, cognitive and behavioral functioning. Based on recent work, we hypothesized that glial activation is a common factor underlying different proposed etiologies for ASD. To investigate the inflammatory and glial alterations in a mouse model of ASD, we injected pregnant mice with 600, 400mg/kg valproic acid (VPA) or saline at E13. VPA-treated mice showed a delay in the development of the righting reflex, and a decrease in social interaction and an increase in anxiety-related behaviors in adulthood. These results validate our mouse model of ASD. Interestingly, animals prenatally exposed to VPA showed an enhanced response to an inflammatory challenge in adulthood, in comparison with control animals. A LPS dose that failed to elicit an inflammatory response in control mice, induced in turn a significant increment in plasma corticosterone and in the spleen levels of the pro-inflammatory cytokines IL-1b and IL-6 in the spleen. However,IL-6 levels in the hippocampus were augmented 2hs after LPS injection in all experimental groups.These results show that animals treated with VPA at E13 show altered behavior related to ASD and an exacerbated inflammation.