title: TiO2 nanoparticle-induced neurotoxicity may be involved in dysfunction of glutamate metabolism and its receptor expression in mice.
abstract: 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. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 655-662, 2016.
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ze
authors.affiliation: Suzhou Environmental Monitor Center, Suzhou, 215004, China.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Su
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Bingqing
authors.initials: B
authors.lastname: Xu
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sheng
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Cui
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Library of Soochow University, Suzhou, 215021, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Yuguan
authors.initials: Y
authors.lastname: Ze
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism; D005972:Glutaminase / Q000235:genetics / Q000378:metabolism; D005973:Glutamine / Q000235:genetics / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009498:Neurotoxins / Q000633:toxicity*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D014025:Titanium / Q000633:toxicity*
chemical_list: D009498:Neurotoxins; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D005973:Glutamine; C009495:titanium dioxide; D018698:Glutamic Acid; D014025:Titanium; D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase
keywords: glutamate receptors; glutamate-glutamine cyclic pathway; hippocampus; mice; titanium dioxide nanoparticles