The tens of thousands of industrial and synthetic chemicals released into the environment have an unknown but potentially significant capacity to interfere with neurodevelopment. Consequently, there is an urgent need for systematic approaches that can identify disruptive chemicals. Little is known about the impact of environmental chemicals on critical periods of developmental neuroplasticity, in large part, due to the challenge of screening thousands of chemicals. Using an integrative bioinformatics approach, we systematically scanned 2001 environmental chemicals and identified 50 chemicals that consistently dysregulate two transcriptional signatures of critical period plasticity. These chemicals included pesticides (e.g., pyridaben), antimicrobials (e.g., bacitracin), metals (e.g., mercury), anesthetics (e.g., halothane), and other chemicals and mixtures (e.g., vehicle emissions). Application of a chemogenomic enrichment analysis and hierarchical clustering across these diverse chemicals identified two clusters of chemicals with one that mimicked an immune response to pathogen, implicating inflammatory pathways and microglia as a common chemically induced neuropathological process. Thus, we established an integrative bioinformatics approach to systematically scan thousands of environmental chemicals for their ability to dysregulate molecular signatures relevant to critical periods of development.

中文翻译：

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对调节关键期可塑性相关基因表达失调的环境化学物质的系统分析揭示了模拟对病原体的免疫反应的常见途径。

释放到环境中的数以万计的工业和合成化学物质具有未知但潜在重要的干扰神经发育的能力。因此，迫切需要能够识别破坏性化学品的系统方法。人们对环境化学物质对发育神经可塑性关键时期的影响知之甚少，这在很大程度上是由于筛选数千种化学物质的挑战。使用综合生物信息学方法，我们系统地扫描了 2001 年的环境化学物质，并确定了 50 种化学物质，这些化学物质持续调节关键期可塑性的两个转录特征。这些化学品包括杀虫剂（如哒螨灵）、抗菌剂（如杆菌肽）、金属（如汞）、麻醉剂（如氟烷）、和其他化学品和混合物（例如，车辆尾气）。在这些不同的化学物质中应用化学基因组富集分析和层次聚类，确定了两组化学物质，其中一种化学物质模拟了对病原体的免疫反应，表明炎症通路和小胶质细胞是一种常见的化学诱导的神经病理过程。因此，我们建立了一种综合生物信息学方法来系统扫描数以千计的环境化学物质，以了解它们调节与关键发育时期相关的分子特征的能力。暗示炎症通路和小胶质细胞是一种常见的化学诱导的神经病理过程。因此，我们建立了一种综合生物信息学方法来系统扫描数以千计的环境化学物质，以了解它们调节与关键发育时期相关的分子特征的能力。暗示炎症通路和小胶质细胞是一种常见的化学诱导的神经病理过程。因此，我们建立了一种综合生物信息学方法来系统扫描数以千计的环境化学物质，以了解它们调节与关键发育时期相关的分子特征的能力。