TiO2 nanoparticles induced hippocampal neuroinflammation in mice

Yuguan Ze; Lei Sheng; Xiaoyang Zhao; Jie Hong; Xiao Ze; Xiaohong Yu; Xiaoyu Pan; Anan Lin; Yue Zhao; Chi Zhang; Qiuping Zhou; Ling Wang; Fashui Hong

doi:10.1371/journal.pone.0092230

TiO2 nanoparticles induced hippocampal neuroinflammation in mice

PLoS One. 2014 Mar 21;9(3):e92230. doi: 10.1371/journal.pone.0092230. eCollection 2014.

Authors

Yuguan Ze¹, Lei Sheng¹, Xiaoyang Zhao¹, Jie Hong¹, Xiao Ze¹, Xiaohong Yu¹, Xiaoyu Pan¹, Anan Lin¹, Yue Zhao¹, Chi Zhang¹, Qiuping Zhou¹, Ling Wang¹, Fashui Hong²

Affiliations

¹ Medical College of Soochow University, Suzhou, China.
² Medical College of Soochow University, Suzhou, China; Jiangsu Province Key Laboratory of Stem Cell Research, Soochow University, Suzhou, China; Cultivation Base of State Key Laboratory of Stem Cell and Biomaterials Built Together by Ministry of Science and Technology and Jiangsu Province, Suzhou, China.

Abstract

Titanium dioxide nanoparticles (TiO2 NPs) have been used in various medical and industrial areas. However, the impacts of these nanoparticles on neuroinflammation in the brain are poorly understood. In this study, mice were exposed to 2.5, 5, or 10 mg/kg body weight TiO2 NPs for 90 consecutive days, and the TLRs/TNF-α/NF-κB signaling pathway associated with the hippocampal neuroinflammation was investigated. Our findings showed titanium accumulation in the hippocampus, neuroinflammation and impairment of spatial memory in mice following exposure to TiO2 NPs. Furthermore, TiO2 NPs significantly activated the expression of Toll-like receptors (TLR2, TLR4), tumor necrosis factor-α, nucleic IκB kinase, NF-κB-inducible kinase, nucleic factor-κB, NF-κB2(p52), RelA(p65), and significantly suppressed the expression of IκB and interleukin-2. These findings suggest that neuroinflammation may be involved in TiO2 NP-induced alterations of cytokine expression in mouse hippocampus. Therefore, more attention should be focused on the application of TiO2 NPs in the food industry and their long-term exposure effects, especially in the human central nervous system.

Publication types

Research Support, Non-U.S. Gov't
Retracted Publication

MeSH terms

Animals
Cytokines / biosynthesis
Female
Hippocampus / metabolism*
Hippocampus / pathology
I-kappa B Kinase / metabolism
I-kappa B Proteins / metabolism
Inflammation / chemically induced
Maze Learning / drug effects
Mice
Motor Activity / drug effects
NF-kappa B / metabolism*
NF-kappa B p52 Subunit / metabolism
Nanoparticles
Titanium / pharmacology*
Toll-Like Receptor 2 / drug effects
Toll-Like Receptor 2 / physiology
Toll-Like Receptor 4 / drug effects
Toll-Like Receptor 4 / physiology
Toll-Like Receptors / metabolism

Substances

Cytokines
I-kappa B Proteins
NF-kappa B
NF-kappa B p52 Subunit
Tlr2 protein, mouse
Tlr4 protein, mouse
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptors
titanium dioxide
Titanium
I-kappa B Kinase

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant No. 81273036, 30901218), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, National New Ideas Foundation of Student of China (grant No. 111028534), and the National Bringing New Ideas Foundation of Student of China (grant No. 57315427, 57315927). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.