Morphological alterations induced by the exposure to TiO(2) nanoparticles in primary cortical neuron cultures and in the brain of rats

Nowadays, nanoparticles (NPs) of titanium dioxide (TiO(2)) are abundantly produced. TiO(2) NPs are present in various food products, in paints, cosmetics, sunscreens and toothpastes. However, the toxicity of TiO(2) NPs on the central nervous system has been poorly investigated until now. The aim of this study was to evaluate the toxicity of TiO(2) NPs on the central nervous system in vitro and in vivo. In cell cultures derived from embryonic cortical brain of rats, a significant decrease in neuroblasts was observed after 24 to 96 h of incubation with TiO(2) NPs (5 to 20 μg/ml). This phenomenon resulted from an inhibition of neuroblast proliferation and a concomitant increase in apoptosis. In the same time, a gliosis, characterized by an increase in proliferation of astrocytes and the hypertrophy of microglial cells, occurred. The phagocytosis of TiO(2) NPs by microgliocytes was also observed. In vivo, after intraperitoneal injection, the TiO(2) NPs reached the brain through the blood brain barrier and the nanoparticles promoted various histological injuries such as cellular lysis, neuronal apoptosis, and inflammation. A reduction of astrocyte population was observed in some brain area such as plexiform zone, cerebellum and subependymal area. An oxidative stress was also detected by immunohistochemistry in neurons of hippocampus, cerebellum and in subependymal area. In conclusion, our study demonstrated clearly the toxic impact of TiO(2) NPs on rat brain and neuronal cells and pointed about not yet referenced toxicity impacts of TiO2 such as the reduction of neuroblast proliferation both in vitro and in vivo.