Abstract # 3108 Combined exposure to air pollution and maternal stress induces sex-specific, autism-like social behavior deficits and gut dysbiosis in mice

Abstract

Autism spectrum disorder (ASD) is characterized by impaired social interaction and communication, engagement in repetitive behaviors, and a sex bias in prevalence (higher in males). Importantly, recent epidemiological studies suggest that maternal exposure to air pollution during pregnancy may increase ASD risk. Furthermore, studies have shown that maternal stress during pregnancy increases the severity of ASD symptoms. Our lab has developed a novel mouse model of combined diesel exhaust particle (DEP) and maternal stress (MS) exposure. We hypothesized that this DEP/MS exposure would induce ASD-like behavioral deficits in male offspring only. In males only, we observed a significantly lower preference for social vs. non-social stimuli in DEP/MS-exposed mice as compared to controls. Moreover, while control males preferred to interact with a novel peer over their cage mate, DEP/MS-exposed males showed the opposite preference. DEP/MS exposure had no effect on repetitive behavior (marble-burying) or on anxiety-like behavior (as measured in an open field) in either sex. Finally, given the high comorbidity of ASD with gastrointestinal issues, we asked whether DEP/MS exposure would alter the composition of the gut microbiome. Our results suggest that DEP/MS exposure alters both alpha and beta diversity in the gut microbiome of male but not female offspring. We are currently using this model to investigating the neuro-immune mechanisms by which DEP/MS exposure induces sex-specific deficits in social behavior.