title: Ultra-trace graphene oxide in a water environment triggers Parkinson's disease-like symptoms and metabolic disturbance in zebrafish larvae.
abstract: Over the past decade, the safety of nanomaterials has attracted attention due to their rapid development. The relevant health threat of these materials remains largely unknown, particularly at environmentally or biologically relevant ultra-trace concentrations. To address this, we first found that graphene oxide (GO, a carbon nanomaterial that receives extensive attention across various disciplines) at concentrations of 0.01 μg/L-1 μg/L induced Parkinson's disease-like symptoms in zebrafish larvae. In this model, zebrafish showed a loss of more than 90% of dopamine neurons, a 69-522% increase in Lewy bodies (α-synuclein and ubiquitin) and significantly disturbed locomotive activity. Moreover, it was also shown that GO was able to translocate from the water environment to the brain and localize to the nucleus of the diencephalon, thereby inducing structural and morphological damage in the mitochondria. Cell apoptosis and senescence were triggered via oxidative stress, as shown by the upregulation of caspase 8 and β-galactosidase. Using metabolomics, we found that the upregulation of amino acid and some fatty acids (e.g. dodecanoic acid, hexadecanoic acid, octadecenoic acid, nonanoic acid, arachidonic acid, eicosanoic acid, propanoic acid and benzenedicarboxylic acid) metabolism and the downregulation of some other fatty acids (e.g. butanoic acid, phthalic acid and docosenoic acid) are linked to these Parkinson's disease-like symptoms. These findings broaden our understanding of nanomaterial safety at ultra-trace concentrations.
authors.affiliation: Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education), Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China.
authors.forename: Chaoxiu
authors.initials: C
authors.lastname: Ren
authors.affiliation: Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education), Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China. Electronic address: huxiangang@nankai.edu.cn.
authors.forename: Xiangang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, General Hospital of Shenyang Military Region, Shenyang 110016, Liaoning Province, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education), Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China. Electronic address: zhouqx@nankai.edu.cn.
authors.forename: Qixing
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D016922:Cellular Senescence / Q000187:drug effects; D006108:Graphite / Q000633:toxicity*; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D055432:Metabolomics; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014867:Water / Q000737:chemistry*; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D014867:Water; D006108:Graphite
keywords: Graphene oxide; Mitochondrion; Nanotoxicology; Parkinson's disease-like symptoms; ROS; Zebrafish