{"title":"CoCrMo nanoparticle induces neurotoxicity mediated via mitochondrial dysfunction: a study model for implant derived nanoparticle effects.","authors":"Priyadarshini Vijayakumar, Yongchao Mou, Xuejun Li, Jahnavi Anil, Neeraja Revi, Kai-Yuan Cheng, Mathew T Mathew, Divya Bijukumar","doi":"10.1080/17435390.2024.2438118","DOIUrl":null,"url":null,"abstract":"<p><p>Toxicity associated with elevated levels of cobalt-chromium-molybdenum (CoCrMo) nanoparticles in total hip replacement (THR) patients has been a rising concern. Recent investigations demonstrated that these particles can induce polyneuropathy in THR patients. The current study aims to address a detailed molecular investigation of CoCrMo nanoparticle-mediated mitochondrial dynamics using induced pluripotent stem cell-derived neurons (iPSC neurons). Telencephalic neurons from iPSCs were used in this study. A statistically significant dose-dependent reduction in membrane potential and mitochondrial superoxide generation was observed after CoCrMo nanoparticle treatment. The gene expression analysis confirmed that the oxidative-specific genes were significantly upregulated in particle-treated cells compared to untreated cells. When iPSCs were exposed to CoCrMo nanoparticles, there was a significant reduction in the area, perimeter, and length of mitochondria. Live cell imaging (mitochondrial tracking) revealed a significant reduction in mitochondrial movements in the presence of CoCrMo nanoparticles. Further protein expression confirmed increased mitochondrial fission in CoCrMo particle-treated cells by significantly upregulating Drp-1 protein and downregulating Mfn-2. In conclusion, the results show that CoCrMo nanoparticles can significantly alter neuronal mitochondrial dynamics. The disturbance in balance restricts mitochondrial movement, reduces energy production, increases oxidative stress, and can cause subsequent neurodegeneration.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"707-723"},"PeriodicalIF":3.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanotoxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17435390.2024.2438118","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/13 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NANOSCIENCE & NANOTECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Toxicity associated with elevated levels of cobalt-chromium-molybdenum (CoCrMo) nanoparticles in total hip replacement (THR) patients has been a rising concern. Recent investigations demonstrated that these particles can induce polyneuropathy in THR patients. The current study aims to address a detailed molecular investigation of CoCrMo nanoparticle-mediated mitochondrial dynamics using induced pluripotent stem cell-derived neurons (iPSC neurons). Telencephalic neurons from iPSCs were used in this study. A statistically significant dose-dependent reduction in membrane potential and mitochondrial superoxide generation was observed after CoCrMo nanoparticle treatment. The gene expression analysis confirmed that the oxidative-specific genes were significantly upregulated in particle-treated cells compared to untreated cells. When iPSCs were exposed to CoCrMo nanoparticles, there was a significant reduction in the area, perimeter, and length of mitochondria. Live cell imaging (mitochondrial tracking) revealed a significant reduction in mitochondrial movements in the presence of CoCrMo nanoparticles. Further protein expression confirmed increased mitochondrial fission in CoCrMo particle-treated cells by significantly upregulating Drp-1 protein and downregulating Mfn-2. In conclusion, the results show that CoCrMo nanoparticles can significantly alter neuronal mitochondrial dynamics. The disturbance in balance restricts mitochondrial movement, reduces energy production, increases oxidative stress, and can cause subsequent neurodegeneration.
期刊介绍:
Nanotoxicology invites contributions addressing research relating to the potential for human and environmental exposure, hazard and risk associated with the use and development of nano-structured materials. In this context, the term nano-structured materials has a broad definition, including ‘materials with at least one dimension in the nanometer size range’. These nanomaterials range from nanoparticles and nanomedicines, to nano-surfaces of larger materials and composite materials. The range of nanomaterials in use and under development is extremely diverse, so this journal includes a range of materials generated for purposeful delivery into the body (food, medicines, diagnostics and prosthetics), to consumer products (e.g. paints, cosmetics, electronics and clothing), and particles designed for environmental applications (e.g. remediation). It is the nano-size range if these materials which unifies them and defines the scope of Nanotoxicology .
While the term ‘toxicology’ indicates risk, the journal Nanotoxicology also aims to encompass studies that enhance safety during the production, use and disposal of nanomaterials. Well-controlled studies demonstrating a lack of exposure, hazard or risk associated with nanomaterials, or studies aiming to improve biocompatibility are welcomed and encouraged, as such studies will lead to an advancement of nanotechnology. Furthermore, many nanoparticles are developed with the intention to improve human health (e.g. antimicrobial agents), and again, such articles are encouraged. In order to promote quality, Nanotoxicology will prioritise publications that have demonstrated characterisation of the nanomaterials investigated.