Nanoparticulate TiO 2 2 ‐mediated inhibition of the Wnt signaling pathway causes dendritic development disorder in cultured rat hippocampal neurons

摘要

Abstract Titanium dioxide nanoparticles (TiO 2 NPs) 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 TiO 2 NPs inhibited development of dendritic morphology and identified possible molecular mechanisms associated with this inhibition in primary cultured rat hippocampal neurons. Results showed that TiO 2 NPs decreased neurite length, the number of branches and the spine density, and impaired mitochondrial function in the developing neurons. Furthermore, TiO 2 NPs 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, TiO 2 NPs 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 TiO 2 NPs 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.