Neurotoxicity and gene-expressed profile in brain-injured mice caused by exposure to titanium dioxide nanoparticles

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in toothpastes, sunscreens, and products for cosmetic purpose that the human use daily. Although the neurotoxicity induced by TiO2 NPs has been demonstrated, very little is known about the molecular mechanisms underlying the brain cognition and behavioral injury. In this study, mice were exposed to 2.5, 5, and 10 mg/kg body weight (BW) TiO2 NPs by nasal administration for 90 consecutive days, respectively, and their brains' injuries and brain gene-expressed profile were investigated. Our findings showed that TiO2 NPs could be translocated and accumulated in brain, led to oxidative stress, overproliferation of all glial cells, tissue necrosis as well as hippocampal cell apoptosis. Furthermore, microarray data showed significant alterations in the expression of 249 known function genes, including 113 genes upregulation and 136 genes downregulation following exposure to 10 mg/kg BW TiO2 NPs, which were associated with oxidative stress, immune response, apoptosis, memory and learning, brain development, signal transduction, metabolic process, DNA repair, response to stimulus, and cellular process. Especially, significant increases in Col1a1, serine/threonine-protein kinase 1, Ctnnb1, cysteine-serine-rich nuclear protein-1, Ddit4, Cyp2e1, and Krev interaction trapped protein 1 (Krit1) expressions and great decreases in DA receptor D2, Neu1, Fc receptor-like molecules, and Dhcr7 expressions following long-term exposure to TiO2 NPs resulted in neurogenic disease states in mice. Therefore, these genes may be potential biomarkers of brain toxicity caused by TiO2 NPs exposure, and the application of TiO2 NPs should be carried out cautiously. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 470-478, 2014.