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

J Toxicol Sci. 2017;42(6):723-729. doi: 10.2131/jts.42.723.

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.

Keywords: Nano-TiO2; Nano-ZnO; Neurite outgrowth; PC12.

MeSH terms

  • Amino Acid Metabolism, Inborn Errors
  • Animals
  • Brain / metabolism
  • Cell Differentiation / drug effects*
  • Cell Survival / drug effects
  • Dental Enamel Hypoplasia
  • Depression, Chemical
  • Diabetes Mellitus
  • Dose-Response Relationship, Drug
  • Dwarfism
  • Intellectual Disability
  • Microcephaly
  • Nanostructures / toxicity*
  • Neuronal Outgrowth / drug effects*
  • Neurons / cytology
  • Olfactory Pathways / metabolism
  • PC12 Cells
  • Rats
  • Titanium / metabolism
  • Titanium / toxicity*
  • Zinc Oxide / metabolism
  • Zinc Oxide / toxicity*

Substances

  • titanium dioxide
  • Titanium
  • Zinc Oxide

Supplementary concepts

  • Alaninuria with Microcephaly, Dwarfism, Enamel Hypoplasia, and Diabetes Mellitus