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

研究免疫系统在调节自闭症谱系障碍母体免疫激活小鼠模型运动行为中的作用

• 批准号: 22KJ3080
• 负责人: Mi Yang
• 金额: $ 1.09万
• 依托单位: Okinawa Institute of Science and Technology Graduate University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2023
• 资助国家: 日本
• 起止时间: 2023-03-08 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22KJ3080/
• 关键词: Neuroimmunity; Cerebellum; Neurodevelopment; Autism

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.

妊娠期间病毒感染触发的母体免疫激活（MIA）诱导胎儿大脑皮层的发育缺陷，依赖于TH17/IL-17途径，导致自闭症谱系障碍（ASD）样症状。然而，MIA对小脑的影响，大脑结构在ASD中最常发现的大脑结构远非明显。该项目的主要目标是提供证据，证据表明MIA通过特定的遗传细胞因子信号传导而通过特定的遗物细胞因子信号传导，并通过在人类ASD中更好地表征了小脑神经病理，而我们的脑电图则是mia fenter mia fort fet fet fort feft fent fent feft fent feft fent feft feft feft fent feft fent feft fent fent fent fent。 MIA诱导胎儿小脑中小脑核令人兴奋的神经元（ECN）的发育改变，无论是在怀孕的中期和晚期。这些数据表明，MIA介导的IFN-β上调导致小脑核发育有缺陷，从而为小脑中细胞因子信号异常的缔合与ASD提供了新的见解。将来，这些发现可能会刺激旨在更好地理解免疫神经相互作用的进一步研究，这最终可能会为减少MIA对胎儿小脑的不利影响的策略发展提供依据。

项目成果

Analysis of defects in fetal cerebellar development and function caused by maternal immune activation

母体免疫激活导致胎儿小脑发育及功能缺陷分析

• 发表时间: 2022
• 作者: Huang Tsung-Yen;Hirota Masato;Sasaki Daiki;Kalra Rajkumar Singh;Chien Hsiao-Chiao;Tamai Miho;Sarkar Shukla;Mi Yang;Miyagi Mio;Seto Yu;Ishikawa Hiroki;Yang Mi
• 通讯作者: Yang Mi

Phosphoenolpyruvate regulates the Th17 transcriptional program and inhibits autoimmunity

• DOI: 10.1016/j.celrep.2023.112205
• 发表时间: 2023-02-28
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Huang，Tsung-Yen;Hirota，Masato;Ishikawa，Hiroki
• 通讯作者: Ishikawa，Hiroki