产前母亲的免疫激活会触发长期的细胞特异性转录组失调,在灵长类后代的杏仁体
Bradley P Ander1,2, Erin L Carlson2,3, Shawn Kamboj4,5
1Department of Neurology, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.
Molecular psychiatry
|December 18, 2025
概括
母亲的产前免疫激活可以改变胎儿的大脑发育,增加神经发育障碍的风险. 这项灵长类动物研究揭示了杏仁体的持久基因表达变化,将早期炎症与自闭症和精神病途径联系起来.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 免疫学 免疫学 免疫学
背景情况:
- 产前暴露于母体免疫激活 (MIA) 与神经发育障碍,如自闭症 (ASD) 和精神分裂症有关.
- 连接早期炎症与长期大脑功能障碍的细胞和分子机制尚未完全理解.
- 动物MIA模型对人类神经发育的翻译相关性有局限性.
研究的目的:
- 为了研究在妊娠早期的过渡性孕产妇免疫反应如何影响非人类灵长类动物 (NHP) 杏仁体的基因表达.
- 确定在发育中的灵长类大脑中受MIA影响的特定细胞类型和分子通路.
- 建立一个转化灵长类动物模型来研究产前免疫攻击和神经发育障碍.
主要方法:
- 利用非人类灵长类动物 (NHP) 的母体免疫激活 (MIA) 模型,通过给孕施用Poly (I:C).
- 从4岁的男性后代收集了杏仁体组织,用于单核RNA测序 (snRNA-seq).
- 分析了超过71,000个核,以确定特定的杏仁体细胞群中的差异表达基因 (DEG).
主要成果:
- 在暴露于MIA的后代的杏仁体中确定了2768个独特的差异表达基因 (DEGs).
- DEGs集中在侧核的刺激/抑制神经元和中央核的微质中.
- 与MIA相关的DEG涉及突触结构,神经传递和神经免疫信号,并且与ASD和精神病风险基因明显重叠.
结论:
- 过渡性产前孕产妇免疫反应会导致长期的,区域和细胞类型特定的转录基因变化,在灵长类的杏仁体.
- 这些发现提供了早期免疫激活和人类神经发育疾病途径之间的直接联系.
- 该NHP MIA模型提供了一个翻译框架,用于理解早期免疫攻击,并为神经发育障碍开发干预措施.
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