Project 3: Neurodevelopmental Toxicology of Autism

University Of California At Davis, Davis CA

Investigators

Linked publications & trials

Abstract

The long range goal is to determine if exposure to environmental toxicants early in development contributes[unreadable] to the etiology of neurodevelopmental disorders such as autism. A related goal is to determine whether[unreadable] susceptibility to autoimmune disease increases the neurotoxicity of environmental contaminants and[unreadable] increases the risk for developing disorders such as autism. Understanding how exposure to environmental[unreadable] toxicants may contribute to the etiology of neurodevelopmental disorders is important so that the exposure[unreadable] risks can be identified and minimized. If immune system dysfunction is found to increase the risk of[unreadable] exposure to environmental toxicants, then exposure limits to toxic substances can be lowered, and children[unreadable] with immune system dysfunction who may be at increase risk can be identified and protected. The specific[unreadable] aims are to expose mouse strains with low (C57BL/6J) or high (SJL mice) susceptibility to autoimmunity[unreadable] perinatally to either methylmercury (MeHg), polychlorinated biphenyl 95 (PCB 95) or polybrominated[unreadable] diphenyl ether 47 (BDE 47). We will then compare the effects of toxicant exposure between these mouse[unreadable] strains on brain development, complex social behaviors, and immune system function. The hypothesis is[unreadable] that perinatal exposure to each of these toxic substances will impair brain development and behavior, and[unreadable] that suscepbility to autoimmune disease will increase the neuro- and immunotoxicity of these agents. We[unreadable] will also explore a potentially new model of autism in mice injected prenatally with unique autoantibodies[unreadable] isolated from the serum of mothers who have given birth to two more more autistic children. Brain[unreadable] development will be examined histologically using stereological procedures and immunohistochemistry.[unreadable] Complex social behaviors will be studied using behavioral testing procedures established in our laboratory[unreadable] that measure social recognition, social interaction and social communication in mice. Immune system status[unreadable] will be established by measuring cytokines, chemokines, immunoglobulins, and quantifying immune system[unreadable] response to antigenic stimulation. In addition, seizure susceptibility will be measured in toxicant-exposed[unreadable] mice as well as measures of synaptic excitibility and plasticity in hippocampal brain slices. These studies will[unreadable] provide critical new information on the role of the immune system and its interaction with environmental[unreadable] contaminants in autism and other neurodevelopmental disorders.