Investigate the role of the immune system in modulating motor behavior in a maternal immune activation mouse model of autism spectrum disorder

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Maternal immune activation (MIA) triggered by viral infection during pregnancy induces developmental defects in the fetal cerebral cortex dependent on the Th17/IL-17 pathway, leading to autism spectrum disorder (ASD)-like symptoms. However, the impact of MIA on cerebellum, the brain structure most constantly found abnormal in ASD, is far from clear.The main goal of this project is to provide evidence that MIA interrupts offspring cerebellar development through a specific maternal cytokine signaling and helps to better characterize cerebellar neuropathology in human ASD.Here we found that MIA impairs murine fetal cerebellum development. MIA induces developmental alterations of excitatory cerebellar nuclei excitatory neurons (eCNs) in the fetal cerebellum, both in the mid and late stages of pregnancy.Importantly, the administration of Interferon beta (IFN-β), a major cytokine produced in MIA, into pregnant mice decreases eCNs in the fetal cerebellum. These data suggest that MIA-mediated upregulation of IFN-β leads to defective cerebellar nuclei development, providing new insights into the association of abnormal cytokine signaling in the cerebellum with ASD. In the future, these finds could stimulate further studies aimed at better understanding the immune-neural interaction, which may ultimately inform the development of strategies to reduce the adverse effects of MIA on the fetal cerebellum.