Triclocarban (TCC) is an antimicrobial ingredient that commonly incorporated in many household and personal care products, raising public concerns about its potential health risks. Previous research has showed that TCC could cross the blood–brain barrier, but to date our understanding of its potential neurotoxicity at human-relevant concentrations remains lacking. In this study, we observed anxiety-like behaviors in mice with continuous percutaneous exposure to TCC. Subsequently, we combined lipidomic, proteomic, and metabolic landscapes to investigate the underlying mechanisms of TCC-related neurotoxicity. The results showed that TCC exposure dysregulated the proteins involved in endocytosis and neurodegenerative disorders in mouse cerebrum. Brain energy homeostasis was also altered, as evidenced by the perturbation of pyruvate metabolism, TCA cycle, and oxidative phosphorylation, which in turn caused mitochondrial dysfunction. Meanwhile, the changing trends of sphingolipid signaling pathway and overproduction of mitochondrial reactive oxygen species (mROS) could enhance the neural apoptosis. The in vitro approach further demonstrated that TCC exposure promoted apoptosis, accompanied by the overproduction of mROS and alteration in the mitochondrial membrane potential in N2A cells. Together, dysregulated endocytosis, mROS-related mitochondrial dysfunction and neural cell apoptosis are considered to be crucial factors for TCC-induced neurotoxicity, which may contribute to the occurrence and development of neurodegenerative disorders. Our findings provide novel perspectives for the mechanisms of TCC-triggered neurotoxicity.

中文翻译：

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综合多组学方法揭示了三氯卡班对小鼠大脑的神经毒性


三氯卡班 (TCC) 是一种抗菌成分，常用于许多家庭和个人护理产品中，引起公众对其潜在健康风险的担忧。先前的研究表明，TCC 可以穿过血脑屏障，但迄今为止，我们对其在人体相关浓度下的潜在神经毒性的了解仍然缺乏。在这项研究中，我们观察到持续经皮接触 TCC 的小鼠出现类似焦虑的行为。随后，我们结合脂质组学、蛋白质组学和代谢景观来研究 TCC 相关神经毒性的潜在机制。结果表明，TCC 暴露导致小鼠大脑中参与胞吞作用和神经退行性疾病的蛋白质失调。丙酮酸代谢、TCA 循环和氧化磷酸化的扰动证明了脑能量稳态也发生了改变，这反过来又导致了线粒体功能障碍。同时，鞘脂信号通路的变化趋势和线粒体活性氧（mROS）的过量产生可以增强神经细胞凋亡。体外方法进一步证明，TCC 暴露促进细胞凋亡，并伴有 N2A 细胞中 mROS 的过量产生和线粒体膜电位的改变。内吞作用失调、mROS 相关线粒体功能障碍和神经细胞凋亡被认为是 TCC 诱导的神经毒性的关键因素，可能导致神经退行性疾病的发生和发展。我们的研究结果为 TCC 引发的神经毒性机制提供了新的视角。