Comparative study of neurologic effects of nano-TiO2 versus SiO2 after direct intracerebral exposure in mice

Abstract

Titanium and silicon dioxide nanoparticles (TiO2 and SiO2 NPs) are now in daily use in many commercial products of which food, sunscreens, toothpastes or cosmetics. However, their effects on human body, especially on the central nervous system, are still unclear. The aim of this study was to determine whether direct exposition of the brain to TiO2 and SiO2 NPs results in alternations in nervous system function. C57Bl6 mice were exposed to 5 and 10 μg doses of TiO2 and SiO2 NPs through intracerebroventricular administration using a stereotaxic approach. Then the neurologic effects were investigated using motor performance parameters, measured on a rotarod at 20 rpm or at an accelerating rod (from 4 to 40 rpm). Before and after injection, motor activity is registered individually for each mouse exposed, once a week, for 8 weeks. Besides, a group of 3 mice is culled at 1, 2, 3, 4 and 8 weeks after exposure in order to study the time dependant effect on the histopathology of the brain (gliosis, inflammatory process...). Both rotarod tests (accelerating and at 20 rpm) showed that TiO2 and SiO2 NPs exposure could significantly impair the motor performances, even several weeks after initial acute exposure. The first examination of the brain histopathology revealed microglial activation. As it appeared to grow throughout the brain in a time dependant manner this suggests the induction of a long lasting neuroinflammation. These primary findings indicated that exposure to TiO2 and SiO2 NPs could possibly impair the locomotor ability and this deficit may be possibly attributed at least to an inflammatory process maintained till 8 weeks after exposure in the mouse brain. To fully investigate the neurotoxicological consequences of TiO2 and SiO2 NPs exposure, brain contents in these NPs will be also investigated as well as other alterations like neurotransmitter levels. These preliminary data already underline the necessity of more in vivo studies to better characterize TiO2 and SiO2 NPs exposure effects especially on human brain for long-term and low-dose treatment.