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Ti O 2 nanoparticle‐induced neurotoxicity may be involved in dysfunction of glutamate metabolism and its receptor expression in mice
Author(s) -
Ze Xiao,
Su Mingyu,
Zhao Xiaoyang,
Jiang Hao,
Hong Jie,
Yu Xiaohong,
Liu Dong,
Xu Bingqing,
Sheng Lei,
Zhou Qiuping,
Zhou Junling,
Cui Jingwen,
Li Kai,
Wang Ling,
Ze Yuguan,
Hong Fashui
Publication year - 2016
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22077
Subject(s) - neurotoxicity , glutamate receptor , metabotropic glutamate receptor , metabotropic glutamate receptor 2 , glutamine , glutaminase , chemistry , glutamine synthetase , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 6 , hippocampal formation , receptor , metabotropic glutamate receptor 5 , hippocampus , metabotropic glutamate receptor 1 , biochemistry , pharmacology , biology , toxicity , endocrinology , amino acid , organic chemistry
Titanium dioxide nanoparticles (TiO 2 NPs) have been used in environmental management, food, medicine, and industry. But TiO 2 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 TiO 2 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 TiO 2 NPs. Furthermore, TiO 2 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 TiO 2 NP‐exposed hippocampus. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 655–662, 2016.