TY - JOUR TI - Atmospheric particulate matter aggravates CNS demyelination through involvement of TLR-4/NF-kB signaling and microglial activation AU - Han, Bing AU - Li, Xing AU - Ai, Ruo-Song AU - Deng, Si-Ying AU - Ye, Ze-Qing AU - Deng, Xin AU - Ma, Wen AU - Xiao, Shun AU - Wang, Jing-Zhi AU - Wang, Li-Mei AU - Xie, Chong AU - Zhang, Yan AU - Xu, Yan AU - Zhang, Yuan A2 - Harvey, Brandon K A2 - Taniguchi, Tadatsugu VL - 11 PY - 2022 DA - 2022/02/24 SP - e72247 C1 - eLife 2022;11:e72247 DO - 10.7554/eLife.72247 UR - https://doi.org/10.7554/eLife.72247 AB - 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 in vivo and in vitro 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. KW - particulate matter KW - CNS demyelination KW - microglia KW - tlr-4/nf-κb signaling JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -