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Autism spectrum disorder (ASD) is a diverse disorder likely caused by a combination of genetic alterations and environmental insult during early development. Recent studies demonstrate that infection during pregnancy increases the risk of the development of ASD in the child. The activation of the immune system in the pregnant mother is thought to lead to immunological alterations that persist in the brain as well as in the peripheral immune system of the offspring. How this contributes to the symptoms and pathology of ASD, such as altered neuronal development, is unclear. Here we use a mouse model for prenatal exposure to maternal inflammation in which the challenged offspring demonstrate altered behaviors relevant to ASD. The central question we want to answer in this study is whether the changed environment in the brain induced by maternal inflammation results in impairments in neuronal development and altered behavior. This proposal is unique because we will use a variety of approaches that have not been previously applied to this non-genetic model of ASD. Moreover, we will test the ability of anti-inflammatory drugs to reverse the deleterious effects of maternal immune activation on neuronal development and behavior. If successful, this approach could have significant therapeutic impact.
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