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斑马鱼行为表型学在表型分析环境相关水平的铅污染物引起的水生神经毒性中的应用。

Zebrafish behavioral phenomics applied for phenotyping aquatic neurotoxicity induced by lead contaminants of environmentally relevant level.

机构信息

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, NO. 44 West Culture Road, 250012, Ji'nan, 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; Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China.

出版信息

Chemosphere. 2019 Jun;224:445-454. doi: 10.1016/j.chemosphere.2019.02.174. Epub 2019 Feb 25.

Abstract

Environmental lead (Pb) exposure is a worldwide threat due to the ubiquitous contamination. Although the adverse effects of Pb on human health have previously been extensively explored, the eco-toxicological effects on aquatic vertebrates still need further investigation. In addition, there is a paucity in the knowledge of behavioral and physiological effects of Pb within the range of environmental relevant concentration (under 100 μg/L) on aquatic organisms such as zebrafish. Herein, we demonstrated that adult male zebrafish (Danio rerio) exposed to Pb at environmental concentration level (1 μg/L, 10 μg/L and 100 μg/L) for 14 days, exhibited obvious neuro-behavioral alteration including disturbed light dark preference, impaired exploratory behaviors and inhibited spatial working memory. The alteration of entire behavioral profiles was further associated with the disturbed expression patterns of mRNA level of key genes involved in neurodevelopment (gap43, syn2a, th, dat, and drd1b), neurotoxic effects (c-fos and gfap), and stress responses (tap, mt1, hsp70, and hsp90). To determine the comprehensively effect of aquatic contaminants on the entire behavioral profiles, behavioral phenomic data were obtained by hierarchical clustering analysis. Overall, we employed behavioral phenomics methods to find that Pb within standard chronic Pb toxic criteria, significantly altered behavioral phenotype and brain physiology, which would exert profound ecological consequences and offer the reference for adjustment of aquatic toxic criteria.

摘要

环境铅(Pb)暴露是一个全球性的威胁,因为它无处不在。尽管 Pb 对人类健康的不良影响以前已经被广泛研究,但它对水生脊椎动物的生态毒理学影响仍需要进一步研究。此外,对于环境相关浓度(低于 100μg/L)范围内 Pb 对水生生物(如斑马鱼)的行为和生理影响的知识还很匮乏。在这里,我们证明了暴露于环境浓度水平(1μg/L、10μg/L 和 100μg/L)下的成年雄性斑马鱼(Danio rerio)在 14 天内表现出明显的神经行为改变,包括光暗偏好紊乱、探索行为受损和空间工作记忆抑制。整个行为特征的改变与参与神经发育(gap43、syn2a、th、dat 和 drd1b)、神经毒性(c-fos 和 gfap)和应激反应(tap、mt1、hsp70 和 hsp90)的关键基因的 mRNA 水平表达模式的紊乱有关。为了确定水生污染物对整个行为特征的综合影响,我们通过层次聚类分析获得了行为表型数据。总的来说,我们采用行为表型学方法发现,在标准慢性 Pb 毒性标准范围内的 Pb 显著改变了行为表型和大脑生理学,这将产生深远的生态后果,并为调整水生毒性标准提供参考。

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