Mouse model of maternal allergic asthma and offspring autism-like behavioral deficits

Mount Holyoke College, South Hadley MA

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Abstract

DESCRIPTION (provided by applicant): The state of the mother's immune system during pregnancy plays an important role in fetal development and disruptions in this immune balance is associated with a range of neuropsychiatric and neurodevelopmental disorders. Epidemiological and clinical studies have revealed various clues that suggest a possible association between autism spectrum disorders (ASD) and family history of immune system dysfunction. Over the past three decades, analogous increases have been reported in both the incidence of ASD and immune-related disorders, particularly allergy and asthma, raising the question of whether allergic asthma and ASD may share common causal links. In fact, mothers of children with ASD have a higher incidence of allergic asthma compared to mothers of typically developing children. These data raise the hypothesis that maternal allergic asthma (MAA) produces autism-specific neurobehavioral deficits in offspring and highlight a yet undetermined link between the maternal immune system and risk of ASD. Using a validated mouse model of allergic asthma, this proposal will employ a range of species-specific behavioral tasks to [1] characterize the specific neurobehavioral consequences of maternal allergic asthma on offspring development, [2] identify critical developmental windows when MAA perturbs development, and [3] explore the role a single asthma-associated cytokine plays in producing neurobehavioral deficits in offspring. This work will determine the extent to which maternal asthma contributes to the cause of ASD and inform future development of therapeutic interventions for mitigating the effects of maternal asthma in at-risk populations.