Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education; National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China; College of Life Sciences, Shaanxi Normal University, Xi'an, China.
School of Geography and Tourism, Shaanxi Normal University, Xi'an, China.
Elife. 2022 Feb 24;11:e72247. doi: 10.7554/eLife.72247.
Atmospheric Particulate Matter (PM) is one of the leading environmental risk factors for the global burden of disease. Increasing epidemiological studies demonstrated that PM plays a significant role in CNS demyelinating disorders; however, there is no direct testimony of this, and yet the molecular mechanism by which the occurrence remains unclear. Using multiple and strategies, in the present study we demonstrate that PM exposure aggravates neuroinflammation, myelin injury, and dysfunction of movement coordination ability via boosting microglial pro-inflammatory activities, in both the pathological demyelination and physiological myelinogenesis animal models. Indeed, pharmacological disturbance combined with RNA-seq and ChIP-seq suggests that TLR-4/NF-kB signaling mediated a core network of genes that control PM-triggered microglia pathogenicity. In summary, our study defines a novel atmospheric environmental mechanism that mediates PM-aggravated microglia pathogenic activities, and establishes a systematic approach for the investigation of the effects of environmental exposure in neurologic disorders.
大气颗粒物（PM）是全球疾病负担的主要环境风险因素之一。越来越多的流行病学研究表明，PM 在中枢神经系统脱髓鞘疾病中起重要作用；然而，目前还没有直接的证据证明这一点，而且其发生的分子机制尚不清楚。本研究采用多种策略，证明 PM 暴露通过增强小胶质细胞的促炎活性，在病理性脱髓鞘和生理性髓鞘发生动物模型中加重神经炎症、髓鞘损伤和运动协调能力障碍。事实上，药理学干扰结合 RNA-seq 和 ChIP-seq 表明，TLR-4/NF-kB 信号转导介导了一个控制 PM 触发小胶质细胞致病性的核心基因网络。总之，我们的研究定义了一个新的大气环境机制，该机制介导了 PM 加重小胶质细胞致病性的作用，并为研究环境暴露对神经疾病的影响建立了一种系统的方法。
