自闭症谱系障碍 (ASD) - 基因,分子和通路签名连接系统性炎症,线粒体功能障碍,跨突触信号和神经发育
Maria Gevezova1,2, Yordan Sbirkov1,2, Victoria Sarafian1,2
1Department of Medical Biology, Medical University of Plovdiv, Bulgaria.
Brain, behavior, & immunity - health
|June 19, 2023
概括
自闭症谱系障碍 (ASD) 可能源于对病毒感染的外周免疫反应,导致神经炎症和线粒体问题,影响大脑发育和社会行为. 这项研究确定了参与这些过程的关键转录因子.
科学领域:
- 神经科学是一个神经科学.
- 基因组学就是基因组学.
- 免疫学 免疫学 免疫学
背景情况:
- 自闭症谱系障碍 (ASD) 研究在识别潜在的分子途径方面面临挑战,尽管数据广泛.
- 关于有助于ASD的特定神经发育机制存在争议.
研究的目的:
- 通过分析大规模基因表达数据集,识别与ASD相关的分子特征和途径.
- 在ASD患者和对照者之间调查大脑组织和外周血液单核细胞 (PBMC) 中基因表达的差异.
主要方法:
- 利用了来自1355名自闭症患者和1110名对照者的基因表达数据的网络,丰富和注释分析.
- 在大脑和PBMC中检查了差异表达的基因,转录和蛋白质.
- 进行转录因子网络分析以确定关键的监管因素.
主要成果:
- 在ASD中确定了八个关键的转录因子 (BCL3,CEBPB,IRF1,IRF8,KAT2A,NELFE,RELA,TRIM28).
- 在PBMC中升级调节的基因网络与免疫-炎症通路 (干扰素α信号传递) 和DNA修复有关.
- 中枢神经系统的基因网络涉及免疫-炎症通路,细胞因子生产,Toll-Like受体信号传递和PI3K-Akt通路.
- 低调的中枢神经系统基因表明了电子运输链的功能障碍.
- 神经发育过程 (轴突发生,神经发生,突触传播) 的异常与社会和神经认知障碍有关.
结论:
- 外周免疫炎症通路的激活,可能来自病毒感染,可能会触发中枢神经系统 (CNS) 神经炎症和线粒体功能障碍.
- 这些过程可以导致异常的跨突触传播和ASD中大脑发育受损.
- 这些发现表明,潜在的防御反应机制有助于ASD病理生理学.
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