Irie Tomohiko, Kawakami Tsuyoshi, Sato Kaoru, Usami Makoto
Division of Pharmacology, National Institute of Health Sciences.
Division of Environmental Chemistry, National Institute of Health Sciences.
J Toxicol Sci. 2017;42(6):723-729. doi: 10.2131/jts.42.723.
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-TiO 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-TiO 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-TiO 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 to 1.0 × 10 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-TiO (1.0 × 10 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-TiO.
纳米材料在我们的日常生活中已被广泛使用，并且也可能引发健康影响和毒性。纳米材料能够从外部转移至包括大脑在内的内部器官。例如，纳米氧化锌和纳米二氧化钛均可通过啮齿动物的嗅觉途径转移至大脑，这可能会对大脑产生毒性作用。尽管已经对纳米氧化锌和纳米二氧化钛对神经元活力或神经元兴奋性的影响进行了研究，但尚无研究聚焦于这些纳米材料如何影响神经元分化和发育。在本研究中，我们调查了纳米氧化锌和纳米二氧化钛对PC12细胞神经突生长的影响，PC12细胞是用于神经元分化的一个有用的模型系统。令人惊讶的是，在细胞活力未受影响的情况下，经7天暴露于纳米氧化锌（浓度范围为1.0×10至1.0×10μg/mL）后，分化的PC12神经突的数量、长度和分支均受到显著抑制。经7天暴露于纳米二氧化钛（1.0×10至1.0μg/mL）后，神经突的数量和长度也受到显著抑制，而纳米二氧化钛并无细胞毒性作用。这些结果表明，亚细胞毒性浓度的纳米氧化锌或纳米二氧化钛可抑制分化的PC12细胞中的神经突生长。
