Atmospheric particulate matter aggravates cns demyelination through involvement of TLR-4/NF-kB signaling and microglial activation.
Bing HanXing LiRuo-Song AiSi-Ying DengZe-Qing YeXin DengWen MaShun XiaoJing-Zhi WangLi-Mei WangChong XieYan ZhangYan XuYuan ZhangPublished in: eLife (2022)
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.
Keyphrases
- particulate matter
- air pollution
- inflammatory response
- lps induced
- rna seq
- single cell
- lipopolysaccharide induced
- neuropathic pain
- toll like receptor
- oxidative stress
- signaling pathway
- immune response
- nuclear factor
- blood brain barrier
- risk assessment
- human health
- genome wide
- traumatic brain injury
- pi k akt
- escherichia coli
- spinal cord injury
- multiple sclerosis
- case control
- cerebral ischemia
- heavy metals
- genome wide identification