Abstract
Autism spectrum disorder (ASD) has emerged as one of the most prevalent and poorly understood disorders of our time. The etiology of autism currently remains poorly understood; however, emerging clinical and experimental evidence suggests central roles for maternal immune activation (MIA) during pregnancy in ASD. In particular, children whose mothers suffered from an infectious disease or other inflammatory conditions during pregnancy are at a substantially higher risk of developing ASD. It has been shown that MIA-induced ASD can be modeled by treating pregnant mice with the viral mimetic polyinosinic-polycytidylic acid (PolyI:C) during key neurodevelopmental time points. In this paradigm, PolyI:C treatment induces systemic inflammatory responses that model MIA during viral infections. Offspring from PolyI:C-treated mothers develop many of the defining features of ASD including defects in social interactions, communicative impairments, and repetitive/stereotyped behaviors, as well as neuropathologies that are commonly observed in human ASD. While the early use of this emerging ASD model system has provided important initial insights into the involvement of gestational immune dysfunction in neurodevelopmental disorder pathogenesis, we have only just begun to scratch the surface in our understanding of how MIA affects brain maturation and contributes to neurodevelopmental disease. Here we describe best practices for how the PolyI:C model of MIA can be used to study autism-related disorders in mice.
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Acknowledgment
We thank Tony Filiano, members of the Lukens lab, and the Center for Brain Immunology and Glia (BIG) for valuable discussions. This work was supported by The Hartwell Foundation (Individual Biomedical Research Award to J.R.L.), the Owens Family Foundation (J.R.L.), and the Simons Foundation Autism Research Initiative (Pilot Award 515305 to J.R.L.). C.R.L. was supported by a NIH National Institute of General Medical Sciences predoctoral training grant (3T32GM008328).
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Lammert, C.R., Lukens, J.R. (2019). Modeling Autism-Related Disorders in Mice with Maternal Immune Activation (MIA). In: Allen, I. (eds) Mouse Models of Innate Immunity. Methods in Molecular Biology, vol 1960. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9167-9_20
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DOI: https://doi.org/10.1007/978-1-4939-9167-9_20
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