Hu Guiling, Wang Kaidong, Wu Chenyang, Liu Qi, Zhang Qianrong, Qi Ai, Huang Min
School of Public Health, Ningxia Medical University, Hui Autonomous Region, Yinchuan, Ningxia, China.
Key Laboratory of Environmental Factors and Chronic Disease Control, the Street of Shengli, Xingqing District, Hui Autonomous Region, No.1160, Yinchuan, Ningxia, China.
J Mol Neurosci. 2025 Jun 26;75(3):83. doi: 10.1007/s12031-025-02374-z.
3-Phenoxybenzoic acid (3-PBA) has been demonstrated to be associated with neurrotoxicity, however, the precise mechanism through which it exerts its neurotoxic effects remains to be fully elucidated. In this study, an investigation was conducted into the neuroimmunotoxicity of 3-PBA from an immunological perspective, with a combination of traditional toxicological methods and computer simulations being utilized in the research process. In vivo, 3-PBA has been shown to cause microstructural damage to early synapses in the mouse brain, which is widely accepted as the primary cause of cognitive dysfunction in mice. In vivo, it has been demonstrated that synaptic damage is induced by the upregulation of complement activity by neuronal pentraxin 2 (NP2), which in turn promotes microglia-mediated synaptic damage. Moreover, molecular docking simulations confirmed the interaction between 3-PBA and NP2. The present findings extend from a neurotoxicity perspective to 3-PBA-associated computer simulations, highlighting NP2 as a molecular initiating protein for 3-PBA-induced neurotoxicity. Additionally, the heightened complement activity downstream facilitated synaptic harm by microglia, causing a decrease in synaptic density and ensuing cognitive impairment. The outcomes of this study expand our knowledge of the neurotoxic nature of 3-PBA and supply hints and a theoretical foundation for evaluating its risks.
3-苯氧基苯甲酸（3-PBA）已被证明与神经毒性有关，然而，其发挥神经毒性作用的确切机制仍有待充分阐明。在本研究中，从免疫学角度对3-PBA的神经免疫毒性进行了研究，研究过程中结合了传统毒理学方法和计算机模拟。在体内，3-PBA已被证明会对小鼠大脑中的早期突触造成微观结构损伤，这被广泛认为是小鼠认知功能障碍的主要原因。在体内，已证明神经元五聚体蛋白2（NP2）上调补体活性会诱导突触损伤，进而促进小胶质细胞介导的突触损伤。此外，分子对接模拟证实了3-PBA与NP2之间的相互作用。本研究结果从神经毒性角度扩展到与3-PBA相关的计算机模拟，突出了NP2作为3-PBA诱导神经毒性的分子起始蛋白。此外，下游补体活性增强促进了小胶质细胞对突触的损害，导致突触密度降低并继而引起认知障碍。本研究结果扩展了我们对3-PBA神经毒性本质的认识，并为评估其风险提供了线索和理论基础。
