Chen Jiangfei, Lei Lei, Mo Wen, Dong Haojia, Li Jiani, Bai Chenglian, Huang Kaiyu, Truong Lisa, Tanguay Robyn L, Dong Qiaoxiang, Huang Changjiang
Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, China.
Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, China.
Aquat Toxicol. 2021 Nov;240:105990. doi: 10.1016/j.aquatox.2021.105990. Epub 2021 Oct 8.
The widespread commercial application of titanium dioxide nanoparticles (TiO NPs) leads to ubiquitous presence of TiO NPs in the aquatic environment, which highlights the necessity to determine their potential adverse effects on aquatic organisms. The developing nerve system is particularly susceptible to environment perturbation. However, few studies have explored the developmental neurobehavioral toxicity of TiO NPs, especially at smaller particle size ranges (≤20 nm) that have relatively longer retention time in the water column. In this study, zebrafish embryos were exposed to non-teratogenic concentrations of 0.1 and 1 mg/L TiO NPs (average size of 14-20 nm) from 8 to 108 h post-fertilization (hpf) followed by various assessments at different time points up to 12 days post-fertilization (dpf). Our findings revealed that 1 mg/L TiO NPs perturbed the motor and social behaviors in larval zebrafish. These behavioral changes were characterized by decreased swimming speed in a locomotor response test at 5 dpf, increased travel distance in a flash stimulus test at 5 dpf, increased preference to the light zone in a light/dark preference test at 10 dpf, and increased mirror attack and percent time spent in the mirror zone in a mirror stimulus response assay at 12 dpf. Mechanistic examinations at 5 dpf revealed elevated cell apoptosis and oxidative stress. Cell apoptosis was characterized by increased acridine orange (AO) positive cells in the olfactory region and neuromasts of the lateral line system. Oxidative stress was characterized by increased lipid peroxidation, increased ROS production, and upregulated catalase (cat) gene expression. In addition, TiO NP exposure also upregulated genes associated with the developmental nervous system such as the growth associated protein 43 (gap43) and proliferating cell nuclear antigen (pcna). Our results suggest that the neurobehavioral changes in larvae exposed to 1 mg/L TiO NPs during early development may result from cell apoptosis and oxidative stress induced neuronal damages.
二氧化钛纳米颗粒（TiO NPs）的广泛商业应用导致其在水生环境中普遍存在，这凸显了确定其对水生生物潜在不利影响的必要性。发育中的神经系统对环境扰动尤为敏感。然而，很少有研究探讨TiO NPs的发育神经行为毒性，特别是在水柱中保留时间相对较长的较小粒径范围（≤20 nm）。在本研究中，斑马鱼胚胎在受精后8至108小时（hpf）暴露于非致畸浓度的0.1和1 mg/L TiO NPs（平均粒径14 - 20 nm），随后在受精后12天（dpf）的不同时间点进行各种评估。我们的研究结果表明，1 mg/L TiO NPs扰乱了斑马鱼幼体的运动和社交行为。这些行为变化的特征包括：在5 dpf的运动反应测试中游泳速度降低、在5 dpf的闪光刺激测试中行进距离增加、在10 dpf的明暗偏好测试中对亮区的偏好增加以及在12 dpf的镜像刺激反应试验中镜像攻击增加和在镜像区停留的时间百分比增加。在5 dpf进行的机制研究表明细胞凋亡和氧化应激增加。细胞凋亡的特征是嗅觉区域和侧线系统神经丘中吖啶橙（AO）阳性细胞增加。氧化应激的特征是脂质过氧化增加、活性氧生成增加以及过氧化氢酶（cat）基因表达上调。此外，TiO NP暴露还上调了与发育神经系统相关的基因，如生长相关蛋白43（gap43）和增殖细胞核抗原（pcna）。我们的结果表明，在早期发育过程中暴露于1 mg/L TiO NPs的幼体的神经行为变化可能是由细胞凋亡和氧化应激诱导的神经元损伤所致。
