Atmospheric particulate matter aggravates CNS demyelination through involvement of TLR-4/NF-kB signaling and microglial activation
- Shaanxi Normal University, China
- First Affiliated Hospital of Zhengzhou University, China
- Shanghai Jiaotong University School of Medicine, China
Abstract
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.
Data availability
Figure 1 - Source Data 1, Figure 2 - Source Data 1, Figure 3 - Source Data 1, Figure 3 - Source Data 1, Figure supplement 1 - Source Data 1 and Figure supplement 2 - Source Data 1 contain the numerical data used to generate the figures. Sequencing data are available through the NCBI Gene Expression Omnibus GSE183099.
Article and author information
Author details
Funding
National Natural Science Foundation of China (82071396)
- Yuan Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Brandon K Harvey, NIDA/NIH, United States
Ethics
Animal experimentation: All experimental procedures and protocols of mice were approved by the Committee on the Ethics of Animal Experiments of Shaanxi Normal University (No. ECES-2015-0247) and were carried out in accordance with the approved institutional guidelines and regulations. C57BL/6 mice (8-10 weeks of age) were purchased from the Fourth Military University (Xi'an, China).
Version history
- Received: July 16, 2021
- Preprint posted: August 10, 2021 (view preprint)
- Accepted: February 18, 2022
- Accepted Manuscript published: February 24, 2022 (version 1)
- Version of Record published: March 3, 2022 (version 2)
- Version of Record updated: March 15, 2022 (version 3)
Copyright
© 2022, Han et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Atmospheric particulate matter aggravates CNS demyelination through involvement of TLR-4/NF-kB signaling and microglial activation
eLife 11:e72247.
https://doi.org/10.7554/eLife.72247
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