title: Nanoparticulate TiO2-mediated inhibition of the Wnt signaling pathway causes dendritic development disorder in cultured rat hippocampal neurons.
abstract: Titanium dioxide nanoparticles (TiO2NPs) are increasingly used in daily life, in industry, and in environmental clearing, but their potential neurodevelopmental toxicity has been highly debated. In this study, we explored whether TiO2NPs inhibited development of dendritic morphology and identified possible molecular mechanisms associated with this inhibition in primary cultured rat hippocampal neurons. Results showed that TiO2NPs decreased neurite length, the number of branches and the spine density, and impaired mitochondrial function in the developing neurons. Furthermore, TiO2NPs significantly reduced the expression of several proteins involved in canonical Wnt3a/β-catenin signaling including Wnt3a, β-catenin, p-GSK-3β, and CyclinD1 and conversely, elevated GSK-3β expression. In addition to altering expression of proteins involved in canonical Wnt3a/β-catenin signaling, TiO2NPs decreased expression of proteins invovled in non-canonical Wnt signaling, including, MKLP1, CRMP3, ErbB4, and KIF17. Taken together, these results indicate that suppression of dendritic development caused by TiO2NPs is associated with inhibition of activation of the Wnt/β-catenin pathway or non-canonical Wnt pathway-induced expression of microtubule cytoskeletal components in the developing neurons. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2139-2149, 2017.
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Food Safety and Nutritional Function, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Yuguan
authors.initials: Y
authors.lastname: Ze
authors.affiliation: Food Department, Jiangsu Food and Pharmaceutical Science College, Huaian, 223303, China.
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Xiaohon
authors.initials: X
authors.lastname: Yu
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sheng
authors.affiliation: Library of Soochow University, Suzhou, China, Suzhou, 215123, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000009:adverse effects*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium / Q000009:adverse effects*; D060449:Wnt Signaling Pathway
chemical_list: C009495:titanium dioxide; D014025:Titanium
keywords: Wnt/β-catenin pathway; dendrtic morphology; non-canonical Wnt pathway; primary cultured hippocampal neurons; titanium dioxide nanoparticles