West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.
College of Life Sciences, Northwest A&F University, Yangling 712100, China.
Sci Total Environ. 2022 Nov 1;845:157047. doi: 10.1016/j.scitotenv.2022.157047. Epub 2022 Jun 30.
Silver nanoparticles (AgNPs) are used in various research fields. Although the neurotoxicity of AgNPs has been explored in animal models and 2D cell-culture models, including human stem cells, these models cannot accurately mimic the development of the human brain. Therefore, the potential mechanisms of AgNPs-induced developmental neurotoxicity in humans are still largely unclear. In this study, cerebral organoids derived from induced pluripotent stem cells were treated with 0.1 μg/mL or 0.5 μg/mL AgNPs for 7 days. At the low concentration (0.1 μg/mL), AgNPs increased the cell proliferation and inhibited the neural apoptosis in the organoids, but impaired the cilium assembly and elongation, which may perturb the cell cycle and induce abnormal cerebral-organoid growth. Conversely, at the high concentration (0.5 μg/mL), AgNPs significantly inhibited cell proliferation and induced apoptosis in cerebral organoids. High-concentration AgNPs reduced the expression and co-localization of the cytoskeleton proteins F-actin, myosin, and tubulin, thereby perturbing neurite growth. In conclusion, AgNPs exposure induces developmental neurotoxic effects in cerebral organoids and is thus a potential congenital risk factor.
银纳米粒子（AgNPs）被广泛应用于各个研究领域。虽然 AgNPs 的神经毒性已在动物模型和 2D 细胞培养模型（包括人类干细胞）中得到了研究，但这些模型并不能准确模拟人类大脑的发育。因此，AgNPs 诱导的发育神经毒性的潜在机制在很大程度上仍不清楚。在这项研究中，用 0.1μg/mL 或 0.5μg/mL 的 AgNPs 处理诱导多能干细胞衍生的脑类器官 7 天。在低浓度（0.1μg/mL）时，AgNPs 增加了类器官中的细胞增殖并抑制了神经细胞凋亡，但破坏了纤毛的组装和伸长，这可能会扰乱细胞周期并导致异常的脑类器官生长。相反，在高浓度（0.5μg/mL）时，AgNPs 显著抑制了脑类器官中的细胞增殖并诱导了细胞凋亡。高浓度 AgNPs 降低了细胞骨架蛋白 F-肌动蛋白、肌球蛋白和微管蛋白的表达和共定位，从而扰乱了神经突的生长。总之，AgNPs 暴露会在脑类器官中引起发育神经毒性作用，因此是一种潜在的先天性风险因素。
