title: Neurotoxicity and gene-expressed profile in brain-injured mice caused by exposure to titanium dioxide nanoparticles.
abstract: 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.
authors.affiliation: Medical College, Soochow University, Suzhou, 215123, China.
authors.forename: Yuguan
authors.initials: Y
authors.lastname: Ze
authors.forename: Renping
authors.initials: R
authors.lastname: Hu
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wang
authors.forename: Xuezi
authors.initials: X
authors.lastname: Sang
authors.forename: Xiao
authors.initials: X
authors.lastname: Ze
authors.forename: Bi
authors.initials: B
authors.lastname: Li
authors.forename: Junju
authors.initials: J
authors.lastname: Su
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Guan
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhao
authors.forename: Suxin
authors.initials: S
authors.lastname: Gui
authors.forename: Liyuan
authors.initials: L
authors.lastname: Zhu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cheng
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Lei
authors.initials: L
authors.lastname: Sheng
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Sun
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D013473:Sunscreening Agents / Q000009:adverse effects* / Q000494:pharmacology; D014025:Titanium / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D009419:Nerve Tissue Proteins; D013473:Sunscreening Agents; C009495:titanium dioxide; D014025:Titanium
keywords: brain damage; gene expression profiling; mice; oxidative stress; titanium dioxide nanoparticles