杨丽华¹,
史奇朋^1,2,
周炳升¹
1. 中国科学院水生生物研究所淡水生态与生物技术国家重点实验室, 武汉 430072;
2. 中国科学院大学, 北京 100049

作者简介: 杨丽华(1984-),女,博士,副研究员,研究方向为环境毒理学,E-mail:lhyang@ihb.ac.cn.

基金项目: 中国科学院战略性先导科技专项(XDB140401)；中国科学院水生生物研究所特色研究所服务项目(Y55Z05)


中图分类号: X171.5

The Effects of BPA on Neurobehavior and Neurotransmitters of Larval Zebrafish (Danio rerio)

Yang Lihua¹,
Shi Qipeng^1,2,
Zhou Bingsheng¹
1. State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;
2. University of Chinese Academy of Sciences, Beijing 100049, China

CLC number: X171.5

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摘要:环境浓度水平下双酚A(BPA)暴露对生物体的毒性效应受到广泛关注。以早期发育阶段斑马鱼为模型,评价了环境浓度下BPA暴露对斑马鱼幼鱼运动行为的影响,并探讨了可能的作用机制。将斑马鱼胚胎暴露于不同浓度BPA(0、1、3、10 和30 mg·L^-1)后,斑马鱼幼鱼的整体平均运动速率显著降低。低浓度组幼鱼在持续光照条件下的运动行为显著降低,同时5-羟色胺受体(htr1a)的转录水平增加十分显著,表明BPA可能通过5-羟色胺受体对斑马鱼的运动行为产生影响。而高浓度组幼鱼在第2个黑暗刺激周期的活动过度受到抑制,同时多巴胺受体(d1r)的转录水平显著降低,表明BPA可能通过多巴胺受体影响斑马鱼对外界刺激的响应。HPLC分析结果表明,5-羟色胺和多巴胺神经递质含量在所有浓度组均显著升高。进一步分析与早期神经发育(wnt1, shha)、单胺类递质神经元分化(lmx1a, nr4a2 和syn2a)以及递质合成(tph1b, th)相关的基因和蛋白水平,发现神经递质含量的升高可能是由于BPA促进了斑马鱼胚胎早期神经发育和单胺类递质神经元的分化。综上,环境浓度下BPA暴露即可对斑马鱼的运行行为产生影响,提示BPA污染很可能对生态环境及人体健康产生潜在的危害。
关键词: 双酚A/
斑马鱼/
神经行为/
神经递质

Abstract:Toxic effects of bisphenol A (BPA) on organisms after exposure to environmentally relevant concentrations have received great concerns. In this study, embryos of zebrafish were exposed to series of concentrations (0, 1, 3, 10 and 30 mg·L^-1) of BPA, and changes in behavior and the underlying mechanisms were studied. Our results indicated that embryonic exposure to BPA caused a significant decrease in average swimming speed of larval zebrafish. Specifically, larval activity was significantly decreased in a continuous light period in groups of lower concentrations and in the next dark stimulating period in groups of higher concentrations after exposure to BPA. Transcriptional changes of htr1a and d1r indicated these receptors might be responsible for the effects observed above. HPLC analysis showed exposure to BPA increased the contents of dopamine and 5-HT at all treatments examined. Further results of expression of genes and proteins related to neurodevelopment of monoamine neurons (wnt1, lmx1a, lmx1a, nr4a2, syn2a) and rate limiting enzymes for synthesis of dopamine and 5-HT (th, tph1b) provided evidences for our hypothesis that BPA could accelerate neurogenesis and neural differentiation thus resulting in increased number of monoamine neurons. Generally, exposure to environmental relevant levels of BPA could affect neurodevelopment and result in behavioral changes in zebrafish larvae, indicating potential risks for wild animals and human due to BPA pollution.
Key words:bisphenol A/
zebrafish/
neurobehavior/
neurotransmitter.