title: Effects of titanium dioxide nanoparticles exposure on parkinsonism in zebrafish larvae and PC12.
abstract: Nanomaterials hold significant potential for industrial and biomedical application these years. Therefore, the relationship between nanoparticles and neurodegenerative disease is of enormous interest. In this contribution, zebrafish embryos and PC12 cell lines were selected for studying neurotoxicity of titanium dioxide nanoparticles (TiO2NPs). After exposure of different concentrations of TiO2NPs to embryos from fertilization to 96 hpf, the hatching time of zebrafish was decreased, accompanied by an increase in malformation rate. However, no significant increases in mortality relative to control were observed. These results indicated that TiO2NPs exposure hold a risk for premature of zebrafish embryos, but not fatal. The further investigation confirmed that TiO2NPs could accumulate in the brain of zebrafish larvae, resulting in reactive oxygen species (ROS) generation and cell death of hypothalamus. Meanwhile, q-PCR analysis showed that TiO2NPs exposure increased the pink1, parkin, α-syn and uchl1 gene expression, which are related with the formation of Lewy bodies. We also observed loss of dopaminergic neurons in zebrafish and in vitro. These remarkable hallmarks are all linked to these Parkinson's disease (PD) symptoms. Our results indicate that TiO2NPs exposure induces neurotoxicity in vivo and in vitro, which poses a significant risk factor for the development of PD.
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Qinglian
authors.initials: Q
authors.lastname: Hu
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Fengliang
authors.initials: F
authors.lastname: Guo
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Fenghui
authors.initials: F
authors.lastname: Zhao
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: azwfu@zjut.edu.cn.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Fu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007814:Larva / Q000187:drug effects; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D016716:PC12 Cells; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000633:toxicity*; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D015027:Zebrafish; D051844:alpha-Synuclein / Q000235:genetics; D029961:Zebrafish Proteins; D000099202:PTEN-Induced Putative Kinase
chemical_list: D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D014025:Titanium; D043222:Ubiquitin Thiolesterase; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; C009495:titanium dioxide; C111567:parkin protein; C558157:Pink1 protein, zebrafish; D029961:Zebrafish Proteins; D000099202:PTEN-Induced Putative Kinase
keywords: Dopamine; Oxidative stress; Parkinson disease; Titanium dioxide nanoparticles; Zebrafish