Academic Journal
Polystyrene nanoplastics induce hippocampal damage and cognitive deficits through oxidative stress-triggered microglial extracellular traps and neuronal ferroptosis.
| Title: | Polystyrene nanoplastics induce hippocampal damage and cognitive deficits through oxidative stress-triggered microglial extracellular traps and neuronal ferroptosis. |
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| Authors: | Hu J; Hubei Clinical Research Center for Alzheimer's Disease, Brain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan, China., Chen Y; Hubei Clinical Research Center for Alzheimer's Disease, Brain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan, China., Xu L; Hubei Clinical Research Center for Alzheimer's Disease, Brain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan, China., Dai A; Hubei Clinical Research Center for Alzheimer's Disease, Brain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan, China., Li J; Hubei Clinical Research Center for Alzheimer's Disease, Brain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, Wuhan, China. Electronic address: lijinquan@wust.edu.cn., Liu X; School of Food Engineering, Moutai Institute, Renhuai, China. Electronic address: xudongliu168@163.com. |
| Source: | Chemico-biological interactions [Chem Biol Interact] 2026 Jul 01; Vol. 434, pp. 112120. Date of Electronic Publication: 2026 May 01. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: Ireland NLM ID: 0227276 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7786 (Electronic) Linking ISSN: 00092797 NLM ISO Abbreviation: Chem Biol Interact Subsets: MEDLINE |
| Imprint Name(s): | Publication: Limerick : Elsevier Original Publication: Amsterdam, Elsevier. |
| MeSH Terms: | Oxidative Stress*/drug effects , Ferroptosis*/drug effects , Hippocampus*/drug effects , Hippocampus*/pathology , Hippocampus*/metabolism , Microglia*/drug effects , Microglia*/metabolism , Microglia*/cytology , Polystyrenes*/chemistry , Polystyrenes*/toxicity , Extracellular Traps*/drug effects , Extracellular Traps*/metabolism , Cognitive Dysfunction*/chemically induced , Cognitive Dysfunction*/pathology , Cognitive Dysfunction*/metabolism , Nanoparticles*/toxicity , Nanoparticles*/chemistry , Microplastics*/toxicity , Microplastics*/chemistry, Neurons/drug effects ; Neurons/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Lipid Peroxidation/drug effects ; Animals ; Mice ; Male ; Mice, Inbred C57BL |
| Abstract: | Exposure to polystyrene nanoplastics (PS-NPs) induces cognitive deficits and hippocampal damage in mice; however, the underlying mechanism remains unclear. The behavioral assessments performed in this study revealed significant impairments in learning and spatial memory in mice exposed to PS-NPs. Mechanistically, PS-NPs triggered oxidative stress in the hippocampus, which activated microglia and drove the excessive formation and release of microglial extracellular traps (MiETs). This sustained neuroinflammatory response, characterized by the release of MiETs and increased levels of proinflammatory cytokines (Tumor Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β)), was closely associated with neuronal ferroptosis. Ultimately, PS-NPs induced hippocampal ferroptosis, as evidenced by the loss of mitochondrial cristae, depletion of glutathione (GSH) and glutathione peroxidase 4 (GPX4), elevated lipid peroxidation, and disrupted iron homeostasis, characterized by reduced ferritin heavy chain 1 (FTH1) expression and increased levels of ferrous iron. Notably, the antioxidant N-acetylcysteine (NAC) effectively attenuated oxidative stress, suppressed microglial activation and MiET formation, and reduced neuroinflammation, thereby preventing neuronal ferroptosis and cognitive impairment. Coculture experiments confirmed that PS-NPs-induced MiETs mediate neuronal ferroptosis, and inhibition of ferroptosis ameliorates PS-NPs-driven neuroinflammation. These results demonstrate that PS-NPs induce cognitive impairment primarily through an oxidative stress-driven cascade involving microglial activation, MiET release, neuroinflammation, and hippocampal ferroptosis. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Cognitive dysfunction; Ferroptosis; Microglial extracellular traps; Oxidative stress; Polystyrene nanoplastics |
| Substance Nomenclature: | 0 (Polystyrenes) 0 (Microplastics) 0 (Tumor Necrosis Factor-alpha) |
| Entry Date(s): | Date Created: 20260503 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260716 |
| DOI: | 10.1016/j.cbi.2026.112120 |
| PMID: | 42070744 |
| Database: | MEDLINE |
| ISSN: | 1872-7786 |
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| DOI: | 10.1016/j.cbi.2026.112120 |