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

孕期病毒感染引发的母体免疫激活(MIA)依赖Th17/IL-17途径诱导胎儿大脑皮层发育缺陷，导致自闭症谱系障碍(ASD)样症状。然而，MIA对小脑的影响还远不清楚，小脑是ASD中最常见的大脑结构异常。本项目的主要目的是提供证据，证明MIA通过特定的母体细胞因子信号转导干扰子代小脑发育，并有助于更好地描述人类ASD的小脑神经病理。米非司酮可诱导妊娠中期和晚期胎儿小脑兴奋性小脑核兴奋性神经元的发育变化，重要的是，孕鼠注射米非司酮产生的主要细胞因子干扰素-β可减少胎儿小脑中的兴奋性小脑核兴奋性神经元的数量。这些数据表明，MIA介导的干扰素-β上调导致小脑核团发育缺陷，为小脑异常细胞因子信号与自闭症的关联提供了新的见解。在未来，这些发现可能会刺激进一步的研究，旨在更好地了解免疫与神经的相互作用，最终可能会为开发减少MIA对胎儿小脑的不利影响的策略提供信息。

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.