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Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway

Authors :
Guanjun Li
Xueyan Liu
Xin Sun
Ling Huang
Wenhua Kuang
Jinhuan Ou
Junzhe Zhang
Ziyue Zhang
Huiying Li
Huan Tang
Chenran Feng
Liwei Gu
Chuanbin Yang
Wang Peili
Jigang Wang
Source :
Environment International, Vol 185, Iss , Pp 108543- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Exposure to environmentally hazardous substances is recognized as a significant risk factor for neurological associated disorders. Among these substances, polystyrene microplastics (PS-MPs), widely utilized in various consumer products, have been reported to exhibit neurotoxicity. However, the potential association of PS-MPs with abnormal anxiety behaviors, along with the underlying molecular mechanisms and key proteins involved, remains insufficiently explored. Here, we delineated the potential mechanisms of PS-MPs-induced anxiety through proteomics and molecular investigations. We characterized the PS-MPs, observed their accumulation in the brain, leading to anxiety-like behavior in mice, which is correlated with microglia activation and pro-inflammatory response. Consistent with these findings, our studies on BV2 microglia cells showed that PS-MPs activated NF-κB-mediated inflammation resulting in the upregulation of pro-inflammatory cytokines such as TNFα and IL-1β. Of particular significance, HRAS was identified as a key factor in the PS-MPs induced pro-inflammatory response through whole proteomics analysis, and knockdown of H-ras effectively inhibited PS-MPs induced PERK-NF-κB activation and associated pro-inflammatory response in microglia cells. Collectively, our findings highlight that PS-MPs induce anxiety of mice via the activation of the HRAS-derived PERK-NF-κB pathway in microlglia. Our results contribute valuable insights into the molecular mechanisms of PS-MPs-induced anxiety, and may offer implications for addressing neurotoxicity and prevention the adverse effects of environmentally hazardous substances, including microplastics.

Details

Language :
English
ISSN :
01604120
Volume :
185
Issue :
108543-
Database :
Directory of Open Access Journals
Journal :
Environment International
Publication Type :
Academic Journal
Accession number :
edsdoj.89b02feadfbe4ee8be04985d7d091572
Document Type :
article
Full Text :
https://doi.org/10.1016/j.envint.2024.108543