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.
Highlights
Titanium dioxide nanoparticles (TiO2 NPs) have been used in the paint industry, medicine, and as additives in food colorants and nutritional products
Win-Shwe et al studied the effect of intranasal instillation of nanoparticulate carbon black (14 nm and 95 nm) on brain cytokine and chemokine mRNA expression in mouse olfactory bulb, and found that exposure to 14-nm carbon black promoted interleukin (IL)-1b, tumor necrosis factor alpha (TNFa), CCL2 and CCL3 mRNA expression in the central nervous system (CNS) [6,7]
TiO2 NPs characteristics XRD measurements show that TiO2 NPs exhibit the anatase structure (Fig. 1), and the average grain size calculated from the broadening of the (101) XRD peak of anatase was roughly 5.5 nm using Scherrer’s equation
Summary
Titanium dioxide nanoparticles (TiO2 NPs) have been used in the paint industry, medicine, and as additives in food colorants and nutritional products. Win-Shwe et al studied the effect of intranasal instillation of nanoparticulate carbon black (14 nm and 95 nm) on brain cytokine and chemokine mRNA expression in mouse olfactory bulb, and found that exposure to 14-nm carbon black promoted interleukin (IL)-1b, tumor necrosis factor alpha (TNFa), CCL2 and CCL3 mRNA expression in the central nervous system (CNS) [6,7]. The intranasal instilled TiO2 NPs produced histopathological changes in the CA1 region of the hippocampus and high inflammatory responses by elevating TNF-a and IL-1b levels [8]. TiO2 NPs significantly promoted lipid peroxidation and protein oxidation in the exposed mice and induced other specific neurochemicals [9,10], increased TNF-a and IL-1b expression and nuclear factor-kB (NF-kB) binding activity by increasing microglial activation in the pre-inflamed brain of mice, and resulted in an exaggerated neuroinflammatory response [11]
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