Liu Chong, Zhao Yan, Zhang Wei, Dao Ji-Ji, Li Qian, Huang Jia, Li Zhen-Feng, Ma Yu-Ke, Qiao Chen-Meng, Cui Chun, Chen Shuang-Xi, Yu Li, Shen Yan-Qin, Zhao Wei-Jiang
MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Department of Cell Biology, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
School of Basic Medical Sciences, Experimental Center for Medical Research, Neurologic Disorders and Regeneration Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang, Shandong, China.
J Neuroinflammation. 2025 Mar 15;22(1):86. doi: 10.1186/s12974-025-03406-6.
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.
聚苯乙烯微塑料（PS-MPs）对神经系统的影响已有文献记载。大量研究表明，表皮生长因子受体4（ErbB4）的激活在神经元损伤和再生过程中至关重要。本研究调查了通过小分子激动剂4-溴-1-羟基-2-萘甲酸（C11H7BrO3，E4A）靶向激活ErbB4受体在减轻PS-MPs诱导的神经元损伤中的作用。研究结果显示，靶向激活ErbB4受体可显著改善暴露于PS-MPs的小鼠的认知行为缺陷。此外，E4A处理上调了胞质分裂 dedicator 3（DOCK3）和沉默调节蛋白3（SIRT3）的表达，并减轻了暴露于PS-MPs的小鼠海马体内的线粒体和突触功能障碍。E4A还减少了TLR4-NF-κB-NLRP3信号通路的激活，从而减轻了神经炎症。体外实验表明，E4A部分减轻了PS-MPs诱导的海马神经元损伤及其对小胶质细胞炎症的影响。总之，本研究结果表明，靶向激活ErbB4受体可能减轻神经元损伤及随后的神经炎症，从而减轻PS-MPs暴露诱导的海马神经元损伤并改善认知功能障碍。这些结果为潜在治疗策略的开发提供了有价值的见解。
