Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by impaired communication, impaired reciprocal social interaction, restricted sociability deficits, and the presence of stereotyped patterns of behaviors. Immune dysregulation has been suggested to play a possible etiological role in ASD. Recent studies have demonstrated that exposure to methylmercury chloride (MeHgCl) leads to abnormal gait, motor deficits, impaired hearing, and memory deficits; however, its effects on behavioral and immunological responses have not been adequately investigated in ASD. In this study, we investigated the effects of MeHgCl exposure on marble burying, self-grooming behaviors, sociability tests, and locomotor activities in BTBR T+ Itpr3tf/J (BTBR) mice. We also explored the possible molecular mechanism underlying the effects of MeHgCl administration on IFN-gamma-, T-bet-, IL-9-, and IL-17A-producing CD4(+), CXCR5(+), CXCR6(+), and CCR9(+) cells isolated from spleens. Furthermore, the effects of MeHgCl exposure on the mRNA expression and levels of pro-inflammatory cytokines in the brain tissue and serum samples were also assessed. Our results demonstrated that MeHgCl exposure caused a significant increase in marble burying, self-grooming behaviors and a decrease in social interactions and adverse effects on locomotor activity in BTBR mice. MeHgCl exposure also significantly increased the production of CD4(+)IFN-gamma(+), CD4(+)T-bet(+), CCR9(+)T-bet(+), CXCR5(+)IL-9(+), CD4(+)IL-9(+), CXCR6(+)IL-17A(+), and CD4(+)IL-17A(+) cells in the spleen. Furthermore, MeHgCl exposure increased mRNA and protein levels of pro-inflammatory cytokines in the brain and serum respectively in BTBR mice. In conclusion, MeHgCl administration aggravated existing behavioral and immune abnormalities in BTBR mice.