Molecular mechanism of hippocampal apoptosis of mice following exposure to titanium dioxide nanoparticles

摘要

Previous studies demonstrate that the exposure to titanium dioxide nanoparticles (TiO_2 NPs) damages the central nervous system of mice; however, very little is known about the effects of TiO_2 NPs on hippocampal apoptosis or its molecular mechanism. The present study investigated the molecular mechanism associated with hippocampal apoptosis in mice induced by intragastric administration of TiO_2 NPs for consecutive 60 days. Our findings indicate that TiO_2 NPs accumulate in the mouse hippocampus, and this accumulation, in turn, led to hippocampal apoptosis and impairment in spatial recognition memory in mice. In addition, TiO_2 NPs significantly activated caspase-3 and -9, inhibited Bcl-2, and promoted the levels of Bax and cytochrome c. Furthermore, TiO_2 NPs induced accumulation of reactive oxygen species in the mouse hippocampus. These findings suggest that TiO_2 NP-induced apoptosis in the mouse hippocampus may result from an intrinsic pathway, and workers and consumers should take great caution when handling nanomaterials.