Asthma-induced ASD-like Behaviors in Offspring of Maternal Allergic-Asthma Dams: A Model of the Double Hit Hypothesis



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Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by social and communication impairments and restricted repetitive behaviors (American Psychiatric Association, 2013). While ASD is based exclusively on behavioral symptomology, many reports note immune dysregulation as a common underlying feature. These immune alterations are thought to begin early in fetal development and population-based studies suggest a link between ASD severity and maternal incidence of allergies and asthma. This project examined the effects of maternal immune activation, via a maternal allergic-asthma (MAA) model, in conjunction with offspring asthma on severity of ASD-like behaviors in mice. It was hypothesized that MAA offspring exposed to repeated asthma inductions throughout juvenile development would exhibit more severe ASD-like behaviors. To test this, female C57BL/6J (C57) mice were sensitized to the egg protein ovalbumin, OVA, or phosphate buffered saline, PBS, and pregnant females were exposed to either aerosolized OVA (i.e. MAA) or PBS- vehicle (i.e. Control), respectively, throughout gestation to elicit allergic-asthma episodes. Following parturition, mice from both MAA and Control dams were randomly assigned to undergo either subsequent OVA sensitizations and inductions or be exposed to PBS sensitizations and inductions. The resulting four groups, (Control-PBS, Control-OVA, MAA-PBS, and MAA-OVA) were then assessed for ASD-like behaviors following acute asthma inductions using a series of well-validated behavioral tasks. Results indicated that allergic-asthma exposure, either during gestation or in the juvenile period, elicited species atypical behaviors in social and anxiety-associated tasks.



Autism Spectrum Disorder, Double Hit Hypothesis, Maternal Allergic Asthma