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产前免疫应激会抑制小质反应,损害神经回路

Lindsay N Hayes¹, Kyongman An², Elisa Carloni²

¹Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

|September 28, 2022

概括

在小鼠中,母体免疫激活会导致后代微质细胞的长期免疫弱,影响大脑发育和电路功能. 将这些微质细胞替换为原始细胞恢复了正常的大脑发育和神经元功能.

科学领域:

神经科学
免疫学
发育生物学

背景情况:

影响神经元功能和电路连接.
孕产妇的环境因素会影响孕前大脑的发育.
产前环境对小质细胞发育和功能的影响尚不清楚.

研究的目的:

研究母体免疫激活 (MIA) 如何影响后代的小质细胞发育轨迹.
了解MIA引起的小质细胞改变对大脑发育和功能的长期影响.

主要方法:

在小鼠中的母体免疫激活 (MIA) 模型.
单细胞RNA测序用于分析微细胞群.
用于研究基因调节的染色质可访问性测试.
微细胞的替代实验

主要成果:

在后代的微质细胞中,MIA导致长期的免疫反应性下降 (缩).
这种减弱与染色质可访问性变化和转录因子结合性降低有关.
在没有形成单独的子群体的情况下,MIA减少了微质对炎症状态的贡献.
将异常的微质细胞替换为原始的微质细胞改善了免疫功能,并恢复了多巴胺受体类型二中等状神经元的正常功能.

结论:

不良的产前环境,如MIA,可能导致长期的微质反应性变化.
异常发育的小质会影响皮带电路的发育和功能.
针对微质发育可能为神经发育障碍提供治疗策略.

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