title: Mechanism of TiO2 nanoparticle-induced neurotoxicity in zebrafish (Danio rerio).
abstract: Zebrafish (Danio rerio) has been used historically for evaluating the toxicity of environmental and aqueous toxicants, and there is an emerging literature reporting toxic effects of manufactured nanoparticles (NPs) in zebrafish embryos. Few researches, however, are focused on the neurotoxicity on adult zebrafish after subchronic exposure to TiO2 NPs. This study was designed to evaluate the morphological changes, alterations of neurochemical contents, and expressions of memory behavior-related genes in zebrafish brains caused by exposures to 5, 10, 20, and 40 μg/L TiO2 NPs for 45 consecutive days. Our data indicated that spatial recognition memory and levels of norepinephrine, dopamine, and 5-hydroxytryptamine were significantly decreased and NO levels were markedly elevated, and over proliferation of glial cells, neuron apoptosis, and TiO2 NP aggregation were observed after low dose exposures of TiO2 NPs. Furthermore, the low dose exposures of TiO2 NPs significantly activated expressions of C-fos, C-jun, and BDNF genes, and suppressed expressions of p38, NGF, CREB, NR1, NR2ab, and GluR2 genes. These findings imply that low dose exposures of TiO2 NPs may result in the brain damages in zebrafish, provide a developmental basis for evaluating the neurotoxicity of subchronic exposure, and raise the caution of aquatic application of TiO2 NPs.
authors: Medical College of Soochow University, Suzhou, 215123, China.
authors: Lei
authors: L
authors: Sheng
authors: Libary of Soochow University, Suzhou, 215021, China.
authors: Ling
authors: L
authors: Wang
authors: Medical College of Soochow University, Suzhou, 215123, China.|Suzhou Environmental Monitor Center, Suzhou, 215004, China.
authors: Mingyu
authors: M
authors: Su
authors: Medical College of Soochow University, Suzhou, 215123, China.
authors: Xiaoyang
authors: X
authors: Zhao
authors: Medical College of Soochow University, Suzhou, 215123, China.
authors: Renping
authors: R
authors: Hu
authors: Medical College of Soochow University, Suzhou, 215123, China.
authors: Xiaohong
authors: X
authors: Yu
authors: Medical College of Soochow University, Suzhou, 215123, China.
authors: Jie
authors: J
authors: Hong
authors: Medical College of Soochow University, Suzhou, 215123, China.
authors: Dong
authors: D
authors: Liu
authors: Medical College of Soochow University, Suzhou, 215123, China.
authors: Bingqing
authors: B
authors: Xu
authors: Medical College of Soochow University, Suzhou, 215123, China.
authors: Yunting
authors: Y
authors: Zhu
authors: Medical College of Soochow University, Suzhou, 215123, China.
authors: Han
authors: H
authors: Wang
authors: Medical College of Soochow University, Suzhou, 215123, China.
authors: Fashui
authors: F
authors: Hong
mesh_terms: D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D053758:Nanoparticles / Q000633:toxicity*; D009457:Neuroglia / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000473:pathology* / Q000523:psychology; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects; D014025:Titanium / Q000633:toxicity*; D015027:Zebrafish
chemical_list: C009495:titanium dioxide; D009569:Nitric Oxide; D006916:5-Hydroxytryptophan; D014025:Titanium; D004298:Dopamine; D009638:Norepinephrine
keywords: TiO2 nanoparticles; brain injury; gene expression; neurotransmitters; zebrafish