TiO2 nanoparticle-induced neurotoxicity may be involved in dysfunction of glutamate metabolism and its receptor expression in mice

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• 作者：Xiao Ze ; Mingyu Su ; Xiaoyang Zhao ; Hao Jiang ; Jie Hong ; Xiaohong Yu ; Dong Liu ; Bingqing Xu ; Lei Sheng ; Qiuping Zhou ; Junling Zhou ; Jingwen Cui ; Kai Li ; Ling Wang ; Yuguan Ze and Fashui Hong
• 关键词：titanium dioxide nanoparticles ; mice ; hippocampus ; glutamate&ndash ; glutamine cyclic pathway ; glutamate receptors
• 刊名：Environmental Toxicology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：31
• 期：6
• 页码：655-662
• 全文大小：491K
• ISSN：1522-7278

文摘

Titanium dioxide nanoparticles (TiO₂ NPs) have been used in environmental management, food, medicine, and industry. But TiO₂ NPs have been demonstrated to cross the blood–brain barrier and store up in the brain organization, leading to glutamate-mediated neurotoxicity. However, the neurotoxicity in the brain is not well understood. In this study, mice were exposed to 1.25, 2.5, or 5 mg/kg body weight TiO₂ NPs for 9 months, and the glutamate–glutamine cyclic pathway and expressions of glutamate receptors associated with the hippocampal neurotoxicity were investigated. Our findings showed elevations of glutamate release and phosphate-activated glutaminase activity, and reductions in glutamine and glutamine synthetase in the hippocampus following exposure to TiO₂ NPs. Furthermore, TiO₂ NPs significantly inhibited the expression of N-methyl-d-aspartate receptor subunits (including NR1, NR2A, and NR2B) and metabotropic glutamate receptor 2 in mouse hippocampus. These findings suggest that the imbalance of glutamate metabolism triggered inhibitions of glutamate receptor expression in the TiO₂ NP-exposed hippocampus.