文献类型：期刊文献

英文题名：TBBPA exposure during a sensitive developmental window produces neurobehavioral changes in larval zebrafish

作者：Chen, Jiangfei[1,2];Tanguay, Robert L.[3,4];Xiao, Yanyan[2];Haggard, Derik E.[3,4];Ge, Xiaoqing[2];Jia, Yinhang[2];Zheng, Yi[2];Dong, Qiaoxiang[2];Huang, Changjiang[2];Lin, Kuangfei[1]

机构：[1]East China Univ Sci & Technol, Sch Resources & Environm Engn, State Environm Protect Key Lab Environm Risk Asse, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[2]Wenzhou Med Univ, Inst Environm Safety & Human Hlth, Wenzhou 325035, Peoples R China;[3]Oregon State Univ, Sinnhuber Aquat Res Lab, Environm & Mol Toxicol, Corvallis, OR 97333 USA;[4]Oregon State Univ, Environm Hlth Sci Ctr, Corvallis, OR 97333 USA

年份：2016

卷号：216

起止页码：53

外文期刊名：ENVIRONMENTAL POLLUTION

收录：;EI(收录号：20162202450053);WOS:【SCI-EXPANDED(收录号:WOS:000383930500007)】；

基金：We thank Dr. Chi-Bin Chien at the University of Utah for the transgenic NBT fish and Hitoshi Okamoto at RIKEN Brain Science Institute for the transgenic Islet fish. This work was supported in part by funding from the National Natural Science Foundation of China (No. 21307096), the National Environmental Protection Public Welfare Science and Technology Research Program of China (No. 201309047) and US EPA STAR grant #R835796.

语种：英文

外文关键词：Zebrafish; TBBPA; Sensitive window; Neurotoxicity; Motor behavior; ugt expression

摘要：Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame retardants (BFRs), is a ubiquitous contaminant in the environment and in the human body. This study demonstrated that zebrafish embryos exposed to TBBPA during a sensitive window of 8-48 h post-fertilization (hpf) displayed morphological malformations and mortality. Zebrafish exposed exclusively between 48 and 96 hpf were phenotypically normal. TBBPA was efficiently absorbed and accumulated in zebrafish embryos, but was eliminated quickly when the exposure solution was removed. Larval behavior assays conducted at 120 hpf indicated that exposure to 5 mu M TBBPA from 8 to 48 hpf produced larvae with significantly lower average activity and speed of movement in the normal condition than in those exposed from 48 to 96 hpf. Specifically, 8-48 hpf-exposed larvae spent significantly less time in both activity bursts and gross movements compared to control or 48-96 hpf exposed larvae. Consistent with the motor deficits, TBBPA induced apoptotic cell death, delayed cranial motor neuron development, inhibited, primary motor neuron development and loosed muscle fiber during the early developmental stages. To further explore TBBPA-induced developmental and neurobehavioral toxicity, RNA-Seq analysis was used to identify early transcriptional changes following TBBPA exposure. In total, 1969 transcripts were significantly differentially expressed (P < 0.05, FDR < 0.05, 1.5-FC) upon TBBPA exposure. Functional and pathway analysis of the TBBPA transcriptional profile identified biological processes involved in nerve development, muscle filament sliding and contraction, and extracellular matrix disassembly and organization changed significantly. In addition, TBBPA also led to an elevation in the expression of genes encoding uridine diphosphate glucuronyl transferases (ugt), which could affect thyroxine (T4) metabolism and subsequently lead to neurobehavioral changes. In summary, TBBPA exposure during a narrow, sensitive developmental window perturbs various molecular pathways and results in neurobehavioral deficits in zebrafish. (C) 2016 Published by Elsevier Ltd.