Autism spectrum disorder (ASD) has been associated with maternal infection during pregnancy in humans and using animal models. In animals, maternal infection during pregnancy reduced gut microbiota diversity and richness, which were accompanied by behaviors associated with ASD in humans. Furthermore, an impoverished microbiome was associated with altered activity of microglia (the immune cells of the central nervous system), indicating gut-immune-brain axis interconnections. Importantly, during development, microglia play a role in removing unnecessary synapses, a process termed synaptic pruning, which is known to be disturbed in ASD.The aim of the proposed research is to determine specific mechanisms through which maternal infection during pregnancy leads to ASD. We hypothesize that maternal infection during pregnancy affects the gut microbiota of the offspring, leading to disruption of microglial activity during development, which leads to abnormal synaptic pruning and behavioral deficits associated with ASD. The proposed project will utilize the maternal immune activation model, an established mouse model of prenatal infection. The offspring of infected mothers will be followed throughout development (neonate, juvenile, and adult). The project will require both in vivo and in vitro techniques in order to adequately assess the effects of maternal infection on gut microbiota, microglial functioning, as well as behavior of the offspring at all stages of life. The proposed project is expected to contribute to the existing body of research linking microbiota and ASD, and might potentially contribute to the development of non-invasive preventative treatments for children whose mothers fell ill during pregnancy.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
