Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model
Abstract The impact of polystyrene microplastics (PS-MPs) on the nervous system has been documented in the literature. Numerous studies have demonstrated that the activation of the epidermal growth factor receptor 4 (ErbB4) is crucial in neuronal injury and regeneration processes. This study investi...
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BMC
2025-03-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03406-6 |
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| author | Chong Liu Yan Zhao Wei Zhang Ji-Ji Dao Qian Li Jia Huang Zhen-Feng Li Yu-Ke Ma Chen-Meng Qiao Chun Cui Shuang-Xi Chen Li Yu Yan-Qin Shen Wei-Jiang Zhao |
| author_facet | Chong Liu Yan Zhao Wei Zhang Ji-Ji Dao Qian Li Jia Huang Zhen-Feng Li Yu-Ke Ma Chen-Meng Qiao Chun Cui Shuang-Xi Chen Li Yu Yan-Qin Shen Wei-Jiang Zhao |
| author_sort | Chong Liu |
| collection | DOAJ |
| description | Abstract The impact of polystyrene microplastics (PS-MPs) on the nervous system has been documented in the literature. Numerous studies have demonstrated that the activation of the epidermal growth factor receptor 4 (ErbB4) is crucial in neuronal injury and regeneration processes. This study investigated the role of targeted activation of ErbB4 receptor through a small molecule agonist, 4-bromo-1-hydroxy-2-naphthoic acid (C11H7BrO3, E4A), in mitigating PS-MPs-induced neuronal injury. The findings revealed that targeted activation of ErbB4 receptor significantly ameliorated cognitive behavioral deficits in mice exposed to PS-MPs. Furthermore, E4A treatment upregulated the expression of dedicator of cytokinesis 3 (DOCK3) and Sirtuin 3 (SIRT3) and mitigated mitochondrial and synaptic dysfunction within the hippocampus of PS-MPs-exposed mice. E4A also diminished the activation of the TLR4-NF-κB-NLRP3 signaling pathway, consequently reducing neuroinflammation. In vitro experiments demonstrated that E4A partially alleviated PS-MPs-induced hippocampal neuronal injury and its effects on microglial inflammation. In conclusion, the findings of this study indicate that targeted activation of ErbB4 receptor may mitigate neuronal damage and subsequent neuroinflammation, thereby alleviating hippocampal neuronal injury induced by PS-MPs exposure and ameliorating cognitive dysfunction. These results offer valuable insights for the development of potential therapeutic strategies. |
| format | Article |
| id | doaj-art-c1c2206263fa403590ffceedfa63847d |
| institution | DOAJ |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-c1c2206263fa403590ffceedfa63847d2025-08-20T03:02:21ZengBMCJournal of Neuroinflammation1742-20942025-03-0122112010.1186/s12974-025-03406-6Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse modelChong Liu0Yan Zhao1Wei Zhang2Ji-Ji Dao3Qian Li4Jia Huang5Zhen-Feng Li6Yu-Ke Ma7Chen-Meng Qiao8Chun Cui9Shuang-Xi Chen10Li Yu11Yan-Qin Shen12Wei-Jiang Zhao13MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Department of Cell Biology, Wuxi School of Medicine, Jiangnan UniversitySchool of Basic Medical Sciences, Experimental Center for Medical Research, Neurologic Disorders and Regeneration Repair Lab of Shandong Higher Education, Shandong Second Medical UniversityMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Department of Cell Biology, Wuxi School of Medicine, Jiangnan UniversityMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Department of Cell Biology, Wuxi School of Medicine, Jiangnan UniversityMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Department of Cell Biology, Wuxi School of Medicine, Jiangnan UniversitySchool of Basic Medical Sciences, Experimental Center for Medical Research, Neurologic Disorders and Regeneration Repair Lab of Shandong Higher Education, Shandong Second Medical UniversityExperimental Center for Medical Research, Shandong Second Medical UniversityRehabilitation Therapy, Medical School, Weifang University of Science and TechnologyMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Department of Neurodegeneration and Neuroinjury, Wuxi School of Medicine, Jiangnan UniversityMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Department of Neurodegeneration and Neuroinjury, Wuxi School of Medicine, Jiangnan UniversityThe First Affiliated Hospital, Department of Neurology, Multi-Omics Research Center for Brain Disorders, Hengyang Medical School, University of South ChinaSchool of Basic Medical Sciences, Experimental Center for Medical Research, Neurologic Disorders and Regeneration Repair Lab of Shandong Higher Education, Shandong Second Medical UniversityMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Department of Neurodegeneration and Neuroinjury, Wuxi School of Medicine, Jiangnan UniversityMOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Department of Cell Biology, Wuxi School of Medicine, Jiangnan UniversityAbstract The impact of polystyrene microplastics (PS-MPs) on the nervous system has been documented in the literature. Numerous studies have demonstrated that the activation of the epidermal growth factor receptor 4 (ErbB4) is crucial in neuronal injury and regeneration processes. This study investigated the role of targeted activation of ErbB4 receptor through a small molecule agonist, 4-bromo-1-hydroxy-2-naphthoic acid (C11H7BrO3, E4A), in mitigating PS-MPs-induced neuronal injury. The findings revealed that targeted activation of ErbB4 receptor significantly ameliorated cognitive behavioral deficits in mice exposed to PS-MPs. Furthermore, E4A treatment upregulated the expression of dedicator of cytokinesis 3 (DOCK3) and Sirtuin 3 (SIRT3) and mitigated mitochondrial and synaptic dysfunction within the hippocampus of PS-MPs-exposed mice. E4A also diminished the activation of the TLR4-NF-κB-NLRP3 signaling pathway, consequently reducing neuroinflammation. In vitro experiments demonstrated that E4A partially alleviated PS-MPs-induced hippocampal neuronal injury and its effects on microglial inflammation. In conclusion, the findings of this study indicate that targeted activation of ErbB4 receptor may mitigate neuronal damage and subsequent neuroinflammation, thereby alleviating hippocampal neuronal injury induced by PS-MPs exposure and ameliorating cognitive dysfunction. These results offer valuable insights for the development of potential therapeutic strategies.https://doi.org/10.1186/s12974-025-03406-6PS-MPsNeuronal damageNeuroinflammationErbB4 receptorSmall moleculeMitochondrial damage |
| spellingShingle | Chong Liu Yan Zhao Wei Zhang Ji-Ji Dao Qian Li Jia Huang Zhen-Feng Li Yu-Ke Ma Chen-Meng Qiao Chun Cui Shuang-Xi Chen Li Yu Yan-Qin Shen Wei-Jiang Zhao Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model Journal of Neuroinflammation PS-MPs Neuronal damage Neuroinflammation ErbB4 receptor Small molecule Mitochondrial damage |
| title | Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model |
| title_full | Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model |
| title_fullStr | Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model |
| title_full_unstemmed | Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model |
| title_short | Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model |
| title_sort | targeted activation of erbb4 receptor ameliorates neuronal deficits and neuroinflammation in a food borne polystyrene microplastic exposed mouse model |
| topic | PS-MPs Neuronal damage Neuroinflammation ErbB4 receptor Small molecule Mitochondrial damage |
| url | https://doi.org/10.1186/s12974-025-03406-6 |
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