分散创伤性脑损伤诱导干扰子刺激器 (STING) 信号在微质驱动皮质神经炎症,神经功能障碍和认知障碍
Jonathan M Packer1, Samantha G Giammo1, Lynde M Wangler1
1The Ohio State University.
Research square
|March 4, 2025
概括
从微质中去除干扰素刺激剂 (STING) 可以减少创伤性脑损伤 (TBI) 后的神经炎症和认知缺陷. 这项研究表明,微质中的STING驱动TBI诱导的炎症和神经元功能障碍.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 创伤性脑损伤 (TBI) 经常导致持续的神经精神问题,如抑郁症和认知障碍.
- 微质介导的炎症反应和I型干扰素 (IFN-I) 信号传递在TBI后过渡到慢性神经炎症的过程中至关重要.
研究的目的:
- 为了研究微质特定的干扰因子刺激器 (STING) 淘汰对TBI诱导的神经炎症,神经元功能障碍和认知障碍的影响.
主要方法:
- 生成和验证的微细胞特异性STING淘汰小鼠 (mSTING-/-).
- 在雄性和雌性小鼠中诱导的扩散性脑损伤 (中线液体打击).
- 评估了受伤后7天 (dpi) 的微质形态,皮质炎症,基因表达 (单核RNA测序),神经元病理和认知功能 (NOR/NOL).
主要成果:
- 创伤增加了STING表达,微质重组和皮质炎症,这些在mSTING小鼠中减弱了.
- 微细胞特异性STING淘汰阻止了皮层神经元中50%的TBI诱导的差异性表达基因,包括抑制CREB和突触生成信号.
- 创伤诱导的神经元损伤标志物 (减少NeuN,增加利波素,增加血神经纤维光链) 和认知缺陷依赖于微质STING.
结论:
- 在微质中切除STING显著减轻TBI诱导的IFN依赖性炎症,神经元功能障碍和认知障碍.
- 微质STING信号传递是慢性神经炎症和TBI后相关病理的关键驱动因素.
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