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Titanium dioxide nanoparticles (TiO 2  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 TiO 2  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 TiO 2  NPs. Furthermore, TiO 2  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 TiO 2  NP-induced alterations of cytokine expression in mouse hippocampus. Therefore, more attention should be focused on the application of TiO 2  NPs in the food industry and their long-term exposure effects, especially in the human central nervous system.

TiO2 Nanoparticles Induced Hippocampal Neuroinflammation in Mice