Involvement of neurotrophins and related signaling genes in TiO2 nanoparticle – induced inflammation in the hippocampus of mice

Abstract

Background: Titanium dioxide nanoparticles (TiO₂ NPs) have been widely used in industry and daily life; their potential neurotoxic effects are of great concern. The aim of this study is to determine whether exposure to TiO₂ NPs mediates neurotrophins and related receptor expression in the hippocampus of mice under TiO₂ NPs-induced neuroinflammation. Methods: Mice were nasally administered with 0.25, 0.5, or 1 mg per kg body weight TiO₂ NPs for nine months. How neurotrophin-related factors and signaling pathways might be affected by exposure to TiO₂ NPs for nine months using real-time PCR and ELISA methods were investigated. Results: The results suggest that exposure to TiO₂ NPs caused TiO₂ NPs deposition, excessive proliferation of all glial cells and tissue necrosis in the hippocampus. The hippocampal injury due to TiO₂ NPs exposure was closely associated with significant reduction in nerve growth factor, brain-derived neurotrophic factor, tyrosine kinases (Trk A, B), calcium/calmodulin-dependent protein kinases (CaMKII, CaMKIV), cyclic-AMP responsive element binding proteins (CREB-1, CREB-2), dopamine receptors (D1, D2) and Tyrosine hydroxylase expression in the hippocampus. Conclusions: The findings imply that long-term exposure to TiO₂ NPs may induce neuroinflammation via impairing neurotrophin-mediated signaling pathways in animals.