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.
Over the past few decades, there has been a coincident rise in both the number of Americans diagnosed with asthma (18.9%) and the incidence of autism spectrum disorders (ASD). Although research points to a link between the mother's immune system (particularly asthma- related immune responses) as a risk factor for having a child with ASD, this association has not yet been experimentally confirmed. This research will use a mouse model to test the extent to which maternal asthma during pregnancy produces autism-like behavioral deficits in offspring. These data will contribute to our understanding of the causes of ASD and inform future interventions to reduce the risk of having a child with this neurodevelopmental disorder.
| Church, Jamie S; Tijerina, Pamella B; Emerson, Felicity J et al. (2018) Perinatal exposure to concentrated ambient particulates results in autism-like behavioral deficits in adult mice. Neurotoxicology 65:231-240 |
| Schwartzer, Jared J; Careaga, Milo; Coburn, Morgan A et al. (2017) Behavioral impact of maternal allergic-asthma in two genetically distinct mouse strains. Brain Behav Immun 63:99-107 |
| Schwartzer, Jared J; Onore, Charity E; Rose, Destanie et al. (2017) C57BL/6J bone marrow transplant increases sociability in BTBR T+ Itpr3tf/J mice. Brain Behav Immun 59:55-61 |
| Rose, Destanie R; Careaga, Milo; Van de Water, Judy et al. (2017) Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation. Brain Behav Immun 63:60-70 |
