Nanosized TiO2 exposure resulted in neurotoxicity via impairing NMDA receptor-mediated postsynaptic signaling cascade in mice

Abstract

The central nervous system (CNS) toxicity induced by exposure to nano-sized particles is of great concern, but the mechanism of how this toxicity may be incurred has yet to be elucidated. Here, we examined how N-methyl-D-aspartate (NMDA) receptor-mediated postsynaptic signaling cascade may be affected by titanium dioxide particles (TiO2 NPs) exposure for six consecutive months to contribute to the observed neurotoxicity. The results suggest that long-term exposure to TiO2 NPs led to titanium accumulation and iron reduction in the blood and hippocampus tissues, and significant hippocampal injury as well as reduction of learning and memory in mice. The CNS injuries following long-term TiO2 NP exposure were closely associated with significant reductions in NR1, NR2A, NR2B, calcium/calmodulin-dependent protein kinase II, postsynaptic density protein 95, nuclear activated extracellular-signal regulated kinase (ERK1/2), Dexras1, CAPON, peripheral benzodiazepine receptor-associated protein, and divalent metal transporter as well as elevation of synaptic Ras GTPase- activating protein and neural nitric oxide synthase in the hippocampus. It implies that long-term exposure to TiO2 NPs may induce neurotoxic effects via impairing NMDA receptor-mediated postsynaptic signaling cascade in animals. © 2014 Sheng L, et al.