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<p>Maternal immune activation (MIA) is a principal environmental risk factor contributing to autism spectrum disorder (ASD) and can be causally linked to ASD symptoms. In our study, we found that MIA triggered by poly (I: C) injection caused ventriculomegaly in offspring due to the dysfunction of the choroid plexus (Chp) and ependyma. We subsequently identified a sustained enhancement of interferon-γ (IFN-γ) signaling in the brain and serum of MIA offspring. Further study revealed that increased IFN-γ signaling could disrupt the barrier function of Chp epithelial cells by activating macrophages, and suppress the differentiation of primary ependymal cells via the signal transducer and activator of transcription 1/3 signaling. The effects of MIA on the offspring were mitigated by administration of IFNGR-blocking antibody in pregnant dams, while systemic maternal administration of IFN-γ was sufficient to mimic the effect of MIA. Overall, our findings revealed that ventriculomegaly caused by IFN-γ signaling could be a critical factor in compromising fetal brain development in MIA-induced ASD and provide a mechanistic framework for the association between maternal inflammation and abnormal development of ventricles in the offspring.</p>

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IFN-γ signaling links ventriculomegaly to choroid plexus and ependyma dysfunction following maternal immune activation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月15日

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  • Yu-Qin Sun,
  • Xin-Xin Huang,
  • Wei Guo,
  • Chen Hong,
  • Juan Ji,
  • Xi-Yue Zhang,
  • Jin Yang,
  • Gang Hu,
  • Xiu-Lan Sun

摘要

Maternal immune activation (MIA) is a principal environmental risk factor contributing to autism spectrum disorder (ASD) and can be causally linked to ASD symptoms. In our study, we found that MIA triggered by poly (I: C) injection caused ventriculomegaly in offspring due to the dysfunction of the choroid plexus (Chp) and ependyma. We subsequently identified a sustained enhancement of interferon-γ (IFN-γ) signaling in the brain and serum of MIA offspring. Further study revealed that increased IFN-γ signaling could disrupt the barrier function of Chp epithelial cells by activating macrophages, and suppress the differentiation of primary ependymal cells via the signal transducer and activator of transcription 1/3 signaling. The effects of MIA on the offspring were mitigated by administration of IFNGR-blocking antibody in pregnant dams, while systemic maternal administration of IFN-γ was sufficient to mimic the effect of MIA. Overall, our findings revealed that ventriculomegaly caused by IFN-γ signaling could be a critical factor in compromising fetal brain development in MIA-induced ASD and provide a mechanistic framework for the association between maternal inflammation and abnormal development of ventricles in the offspring.