Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, NO. 44 West Culture Road, Ji'nan 250012, Shandong Province, PR China.
Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, PR China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, PR China.
Sci Total Environ. 2021 Jan 15;752:141878. doi: 10.1016/j.scitotenv.2020.141878. Epub 2020 Aug 21.
Larval zebrafish (Danio rerio) is not only an ideal vertebrate applied in Fish Embryos Toxicity (FET) test but also a well-accepted model in behavioral neurotoxicity research. By applying the commercial standard behavioral tracking system (Zebrabox), the locomotion profiles (neurobehavioral-phenomics) of larval zebrafish can be comprehensively monitored and systematically analyzed to probe ecotoxicological neurotoxicity of nano-pollutants at environmental relevant concentration level.
Herein, the potential toxicity of at environment relevant concentration level on embryonic zebrafish was evaluated by FET and neurobehavioral-phenomics (NBP). The embryos were exposed to the environmental relevant concentration (0.05, 0.1,1, 5, 10, 100 μg/L). The FET criteria were utilized to evaluate the ecotoxicological effect induced by silica NPs. Subsequently, behavioral neurotoxicity of silica NPs was further quantified via locomotion response (LMR). Specifically, the alteration of Light/Dark challenge (LDC) evoked by light/dark stimulation was detected and analyzed by commercially standard behavioral protocols using zebrabox. We revealed that the exposures of silica NPs at environmental relevant concentration (0.05, 0.1, 1, 5, 10,100 μg/L) significantly disturbed locomotion profiles of larval zebrafish. Additionally, it was obviously noted that low, environmentally relevant silica concentrations might result in altering the total behavioral profiles in developing zebrafish.
In sum, neurobehavior phenomics profiling based on LMR and LDC is a potent methodology for the evaluation of sub-lethal or sub-teratogenic toxicity. Compared with the FET tests characterized by the detection of embryonic teratogenicity, the neurobehavior phenomics based method can be more sensitive to determine sub-teratogenic toxicity of silica NPs at environmental concentrations. With the combination of multivariate data analysis, this approach would offer effective technical reference for environmental nano-toxicology research.
幼体斑马鱼（Danio rerio）不仅是鱼类胚胎毒性（FET）测试中理想的脊椎动物模型，也是行为神经毒性研究中广泛接受的模型。通过应用商业标准行为跟踪系统（Zebrabox），可以全面监测和系统分析幼体斑马鱼的运动特征（神经行为表型），以探究纳米污染物在环境相关浓度水平下的生态毒性神经毒性。
本文采用 FET 和神经行为表型（NBP）评价了环境相关浓度对胚胎斑马鱼的潜在毒性。将胚胎暴露于环境相关浓度（0.05、0.1、1、5、10、100μg/L）下。利用 FET 标准评价了硅纳米颗粒引起的生态毒性效应。随后，通过运动反应（LMR）进一步量化了硅纳米颗粒的行为神经毒性。具体来说，通过斑马鱼盒中的商业标准行为方案，检测和分析了光/暗刺激引起的光/暗挑战（LDC）的变化。结果表明，硅纳米颗粒在环境相关浓度（0.05、0.1、1、5、10、100μg/L）下暴露会显著干扰幼体斑马鱼的运动特征。此外，明显注意到低浓度的环境相关硅浓度可能导致发育中的斑马鱼的总行为特征发生改变。
总之，基于 LMR 和 LDC 的神经行为表型分析是评估亚致死或亚致畸毒性的有效方法。与以检测胚胎致畸性为特征的 FET 测试相比，基于神经行为表型的方法可以更灵敏地确定环境浓度下硅纳米颗粒的亚致畸毒性。结合多元数据分析，这种方法将为环境纳米毒理学研究提供有效的技术参考。
