Chen Jingrong, Chen Cheng, Wang Na, Wang Chunyu, Gong Zhaohui, Du Jingxian, Lai Honglin, Lin Xinpei, Wang Wei, Chang Xiangyu, Aschner Michael, Guo Zhenkun, Wu Siying, Li Huangyuan, Zheng Fuli
Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian Province, China.
Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian Province, China; Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian Province, China; The key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian Province, China.
Neurotoxicology. 2023 Mar;95:155-163. doi: 10.1016/j.neuro.2023.01.010. Epub 2023 Jan 27.
Exposure to cobalt nanoparticles (CoNPs) has been associated with neurodegenerative disorders, while the mitochondrial-associated mechanisms that mediate their neurotoxicity have yet to be fully characterized. In this study, we reported that CoNPs exposure reduced the survival and lifespan in the nematodes, Caenorhabditis elegans (C. elegans). Moreover, exposure to CoNPs aggravated the induction of paralysis and the aggregation of β-amyloid (Aβ). These effects were accompanied by reactive oxygen species (ROS) overproduction, ATP reduction as well as mitochondrial fragmentation. Dynamin-related protein 1 (drp-1) activation and ensuing mitochondrial fragmentation have been shown to be associated with CoNPs-reduced survival. In order to address the role of mitochondrial damage and ROS production in CoNPs-induced Aβ toxicity, the mitochondrial reactive oxygen species scavenger mitoquinone (Mito Q) was used. Our results showed that Mito Q pretreatment alleviated CoNPs-induced ROS generation, rescuing mitochondrial dysfunction, thereby lessening the CoNPs-induced Aβ toxicity. Taken together, we show for the first time, that increasing of ROS and the upregulation of drp-1 lead to CoNPs-induced Aβ toxicity. Our novel findings provide in vivo evidence for the mechanisms of environmental toxicant-induced Aβ toxicity, and can afford new modalities for the prevention and treatment of CoNPs-induced neurodegeneration.
接触钴纳米颗粒（CoNPs）与神经退行性疾病有关，而介导其神经毒性的线粒体相关机制尚未完全明确。在本研究中，我们报告了CoNPs暴露会降低线虫秀丽隐杆线虫（C. elegans）的存活率和寿命。此外，暴露于CoNPs会加重麻痹的诱导和β-淀粉样蛋白（Aβ）的聚集。这些影响伴随着活性氧（ROS）的过量产生、ATP减少以及线粒体碎片化。动力相关蛋白1（drp-1）的激活及随之而来的线粒体碎片化已被证明与CoNPs降低的存活率有关。为了研究线粒体损伤和ROS产生在CoNPs诱导的Aβ毒性中的作用，我们使用了线粒体活性氧清除剂米托醌（Mito Q）。我们的结果表明，Mito Q预处理减轻了CoNPs诱导的ROS生成，挽救了线粒体功能障碍，从而减轻了CoNPs诱导的Aβ毒性。综上所述，我们首次表明，ROS的增加和drp-1的上调导致CoNPs诱导的Aβ毒性。我们的新发现为环境毒物诱导的Aβ毒性机制提供了体内证据，并可为预防和治疗CoNPs诱导的神经退行性变提供新的模式。
