四溴双酚A对斑马鱼胚胎发育和神经行为毒性效应研究

项目名称： 四溴双酚A对斑马鱼胚胎发育和神经行为毒性效应研究

项目编号： No.21307096

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 环境科学、安全科学

项目作者： 陈将飞

作者单位： 温州医科大学

项目金额： 25万元

中文摘要： 四溴双酚A（TBBPA）是被广泛应用的溴代阻燃剂，已在生物体和人体中普遍检出。申请人前期研究发现，TBBPA对斑马鱼胚胎发育具有显著毒性，尤其是对神经行为的影响。由于它的结构与双酚A类似，而后者又与雌激素相关受体ERRγ具有很高的结合力，所以申请人认为TBBPA也可能是通过与ERRγ受体的结合而产生神经毒性的。针对这一科学假设，本项目拟以斑马鱼为模式动物，采用传统毒理学和现代分子生物学研究手段，通过TBBPA急慢性暴露：1）确定TBBPA暴露对斑马鱼神经发育和行为运动的毒性表型；2）RNA-Seq分析TBBPA毒性的分子机制，高通量筛选TBBPA响应的敏感基因和可能的信号通路与靶蛋白；3）确认ERRγ受体在TBBPA神经毒性过程中的作用，探索是否对斑马鱼具有长期的发育神经毒性？研究结果不仅可诠释TBBPA的神经毒性作用机制，而且可为人类健康风险评价提供科学依据。

中文关键词： 斑马鱼；TBBPA；行为表型；神经毒性机制；环境安全风险

英文摘要： Tetrabromobisphenol A (TBBPA), a wildly used bromination flame retardant, has been detected in biota and human tissue. Our previous study found that TBBPA has obviously developmental, and significantly neurobehavioral toxicity in zebrafish embryo. The structure similar compound bisphenol A (BPA), whose toxic target is through strong binding affinity for estrogen related receptor gamma (ERRγ). Therefore, we propose a hypothesis that TBBPA induced toxicity by combining with ERR γ receptor. This proposal will use zebrafish as the model animal and take the advantage of the modern molecular and epigenetic techniques in combination with variety toxicology methods to reveal the underlying mechanism for TBBPA-induced developmental and neurobehavioral toxicity. Using the acute or chronic TBBPA exposure, we will achieve the following objectives: 1) determine the developmental and neurobehavioral phenotypes, and the sensitive exposure window and dose effect; 2) use RNA-Seq analysis to study TBBPA toxic molecular mechanism, high throughput screening the effect genes, possible signal pathways and target proteins; 3) confirm the role of ERR γ receptor in TBBPA induced neurobehavioral toxicity, exploring whether ERR γ down-regulation and TBBPA exposure in embryonic period has the long-term developmental and neurobehavioral tox

英文关键词： Zebrafish；TBBPA；Behavioral phenotypes；Neurotoxicity mechanism；Environmental safety risk