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Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway
Graphical abstract Display Omitted
Highlights PS-MPs induced anxiety-like behavior and accumulated in the brain of mice. PS-MPs-induced toxicity was related to inflammation pathways. HRAS was identified as a key factor in PS-MPs induced pro-inflammatory response. HRAS induced PERK-NF-κB pathway played a significant role in PS-MPs induced toxicity.
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.
Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway
Graphical abstract Display Omitted
Highlights PS-MPs induced anxiety-like behavior and accumulated in the brain of mice. PS-MPs-induced toxicity was related to inflammation pathways. HRAS was identified as a key factor in PS-MPs induced pro-inflammatory response. HRAS induced PERK-NF-κB pathway played a significant role in PS-MPs induced toxicity.
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.
Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway
Li, Guanjun (Autor:in) / Liu, Xueyan (Autor:in) / Sun, Xin (Autor:in) / Huang, Ling (Autor:in) / Kuang, Wenhua (Autor:in) / Ou, Jinhuan (Autor:in) / Zhang, Junzhe (Autor:in) / Zhang, Ziyue (Autor:in) / Li, Huiying (Autor:in) / Tang, Huan (Autor:in)
28.02.2024
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
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