title: Neurotoxic characteristics of spatial recognition damage of the hippocampus in mice following subchronic peroral exposure to TiO2 nanoparticles.
abstract: Due to the increased application of titanium dioxide nanoparticles (TiO2 NPs) in various areas, numerous studies have been conducted which have confirmed that exposure to TiO2 NPs may result in neurological damage in both mice and rats. However, very few studies have focused on the molecular mechanisms of spatial recognition injury. In the present study, to understand the possible neurobiological responses of the mouse hippocampus following subchronic peroral exposure to low level TiO2 NPs, mice were exposed to 2.5, 5, and 10mg/kg body weight TiO2 NPs for 90 consecutive days. Hippocampal pathology and neuron ultrastructure, and long-term potentiation (LTP) were then evaluated, and the hippocampal mRNA-expression of several genes and their proteins involved in homeostasis of neuronal synaptic plasticity were investigated using a quantitative real-time PCR and ELISA method. We observed that subchronic peroral exposure to TiO2 NPs caused severe pathological changes, spatial recognition impairment, and resulted in significant LTP reduction and down-regulation of N-methyl-D-aspartate (NMDA) receptor subunits (NR2A and NR2B) expression associated with the simultaneous inhibition of CaMKIV, cyclic-AMP responsive element binding proteins (CREB-1, CREB-2), and FosB/DFosB in mouse hippocampal tissues. Therefore, our findings suggest that the application of TiO2 NPs in the various areas should be paid more attention.
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: Lei
authors.initials: L
authors.lastname: Sheng
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: Xiao
authors.initials: X
authors.lastname: Ze
authors.affiliation: Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Xuecen
authors.initials: X
authors.lastname: Wang
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: Jialiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Suxin
authors.initials: S
authors.lastname: Gui
authors.affiliation: Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Xuezi
authors.initials: X
authors.lastname: Sang
authors.affiliation: Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Sun
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: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Medical College of Soochow University, Suzhou 215123, China. Electronic address: bingyanli@suda.edu.cn.
authors.forename: Bingyan
authors.initials: B
authors.lastname: Li
authors.affiliation: Medical College of Soochow University, Suzhou 215123, China; Jiangsu Province Key Laboratory of Stem Cell Research, Soochow University, 708 Renmin Road, Suzhou 215007, China; Cultivation base of State Key Laboratory of Stem Cell and Biomaterials built together by Ministry of Science and Technology and Jiangsu Province, Suzhou 215007, China. Electronic address: hongfsh_cn@sina.com.
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000648:ultrastructure; D017774:Long-Term Potentiation / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013037:Spatial Behavior / Q000187:drug effects*; D014025:Titanium / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*
chemical_list: D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; C009495:titanium dioxide; D014025:Titanium
keywords: Hippocampus; Mice; N-methyl-D-aspartate receptor subunits.; Spatial recognition; Titanium dioxide nanoparticles