Neurotoxic characteristics of spatial recognition damage of the hippocampus in mice following subchronic peroral exposure to TiO_2 nanoparticles

摘要

Due to the increased application of titanium dioxide nanoparticles (TiO_2 NPs) in various areas, numerous studies have been conducted which have confirmed that exposure to TiO_2 NPs may result in neurological damage in both mice and rats. However, very few studies have focused on the molecular mechanisms of spatial recognition injury. In the present study, to understand the possible neurobiological responses of the mouse hippocampus following subchronic peroral exposure to low level TiO_2 NPs, mice were exposed to 2.5, 5, and 10 mg/kg body weight TiO_2 NPs for 90 consecutive days. Hippocampal pathology and neuron ultrastructure, and long-term potentiation (LTP) were then evaluated, and the hippocampal mRNA-expression of several genes and their proteins involved in homeostasis of neuronal synaptic plasticity were investigated using a quantitative real-time PCR and ELISA method. We observed that subchronic peroral exposure to TiO_2 NPs caused severe pathological changes, spatial recognition impairment, and resulted in significant LTP reduction and down-regulation of N-methyl-D-aspartate (NMDA) receptor subunits (NR2A and NR2B) expression associated with the simultaneous inhibition of CaMKIV, cyclic-AMP responsive element binding proteins (CREB-1, CREB-2), and FosB/DFosB in mouse hippocampal tissues. Therefore, our findings suggest that the application of TiO_2 NPs in the various areas should be paid more attention.