Sub-toxic concentrations of nano-ZnO and nano-TiO₂ suppress neurite outgrowth in differentiated PC12 cells

Abstract

Nanomaterials have been extensively used in our daily life, and may also induce health effects and toxicity. Nanomaterials can translocate from the outside to internal organs, including the brain. For example, both nano-ZnO and nano-TiO₂ translocate into the brain via the olfactory pathway in rodents, possibly leading to toxic effects on the brain. Although the effects of nano-ZnO and nano-TiO₂ on neuronal viability or neuronal excitability have been studied, no work has focused on how these nanomaterials affect neuronal differentiation and development. In this study, we investigated the effects of nano-ZnO and nano-TiO₂ on neurite outgrowth of PC12 cells, a useful model system for neuronal differentiation. Surprisingly, the number, length, and branching of differentiated PC12 neurites were significantly suppressed by the 7-day exposure to nano-ZnO (in the range of 1.0 × 10^-4 to 1.0 × 10^-1 µg/mL), at which the cell viability was not affected. The number and length were also significantly inhibited by the 7-day exposure to nano-TiO₂ (1.0 × 10^-3 to 1.0 µg/mL), which did not have cytotoxic effects. These results demonstrate that the neurite outgrowth in differentiated PC12 cells was suppressed by sub-cytotoxic concentrations of nano-ZnO or nano-TiO₂.