Grant: Project Grant

Neurodevelopmental disorders (NDDs) are a heterogeneous group of neuropsychiatric illnesses including autism spectrum disorder (ASD) with various degrees of social, cognitive, language and affective deficits. NDDs are caused by aberrant brain development due to genetic and environmental perturbations. Although research on the etiology of NDDs has focused largely on genetic causes, genetic factors seem to account for at most 30-40% of all cases of NDDs. It remains unclear regarding the role of environmental insults in NDD etiology. Mercury as a bioaccumulated environmental toxicant, which can pass through the blood-brain barrier and the placenta, is known to be associated with the delayed effect of NDD in later life. Our recent work using a rodent model showed that low-dose mercury can cause abnormal cerebral cortex development during fetal stage, and that the prenatal low dose mercury exposure led to ASD-like behaviors in their off-springs. In the current proposal we will use both human and rodent models to understand underlying molecular mechanisms that are responsible for mercury-induced abnormal cortical development and ASD-like behavior. We will elucidate how low-dose MeHg impacts cerebral cortical development and ASD-related phenotypes at the cellular, molecular and system levels. Understanding of the underling cellular and molecular mechanisms will lend us a hand to identify therapeutic targets that could be used as biomarkers for early detection of NDDs and provide targeted therapies to prevent NDD onset.