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The developmental neurotoxicity of polybrominated diphenyl ethers: Effect of DE-71 on dopamine in zebrafish larvae.
Environmental Toxicology and Chemistry ( IF 4.1 ) Pub Date : 2015 May , DOI: 10.1002/etc.2906
Xianfeng Wang 1, 2 , Lihua Yang 1 , Yuanyuan Wu 3 , Changjiang Huang 3 , Qiangwei Wang 1, 2 , Jian Han 1, 2 , Yongyong Guo 1 , Xiongjie Shi 1 , Bingsheng Zhou 1
Affiliation  

The potential neurotoxicity of polybrominated diphenyl ethers (PBDEs) is still a great concern. In the present study, the authors investigated whether exposure to PBDEs could affect the neurotransmitter system and cause developmental neurotoxicity in zebrafish. Zebrafish embryos (2 h postfertilization) were exposed to different concentrations of the PBDE mixture DE-71 (0-100 mug/L). The larvae were harvested at 120 h postfertilization, and the impact on dopaminergic signaling was investigated. The results revealed significant reductions in content of whole-body dopamine and its metabolite, dihydroxyphenylacetic acid, in DE-71-exposed larvae. The transcription of genes involved in the development of dopaminergic neurons (e.g., manf, bdnf, and nr4a2b) was significantly downregulated upon exposure to DE-71. Also, DE-71 resulted in a significant decrease of tyrosine hydroxylase and dopamine transporter protein levels in dopaminergic neurons. The expression level of tyrosine hydroxylase in forebrain neurons was assessed by whole-mount immunofluorescence, and the results further demonstrated that the tyrosine hydroxylase protein expression level was reduced in dopaminergic neurons. In addition to these molecular changes, the authors observed reduced locomotor activity in DE-71-exposed larvae. Taken together, the results of the present study demonstrate that acute exposure to PBDEs can affect dopaminergic signaling by disrupting the synthesis and transportation of dopamine in zebrafish, thereby disrupting normal neurodevelopment. In accord with its experimental findings, the present study extends knowledge of the mechanisms governing PBDE-induced developmental neurotoxicity.

中文翻译:

多溴联苯醚的发育性神经毒性:DE-71对斑马鱼幼虫中多巴胺的影响。

多溴二苯醚(PBDEs)的潜在神经毒性仍然是一个令人关注的问题。在本研究中,作者调查了多溴二苯醚的暴露是否会影响神经递质系统并引起斑马鱼的发育性神经毒性。将斑马鱼的胚胎(受精后2小时)暴露于不同浓度的PBDE混合物DE-71(0-100杯/升)中。受精后120小时收获幼虫,并研究其对多巴胺能信号传导的影响。结果表明,暴露于DE-71的幼虫体内多巴胺及其代谢产物二羟基苯乙酸的含量显着降低。暴露于DE-71后,涉及多巴胺能神经元发育的基因(例如manf,bdnf和nr4a2b)的转录显着下调。还,DE-71导致多巴胺能神经元中的酪氨酸羟化酶和多巴胺转运蛋白水平显着降低。整装免疫荧光法检测前脑神经元中酪氨酸羟化酶的表达水平,结果进一步证明酪氨酸羟化酶蛋白在多巴胺能神经元中的表达水平降低。除了这些分子变化外,作者还观察到暴露于DE-71的幼虫的运动活性降低。两者合计,本研究的结果表明,急性暴露于多溴二苯醚会破坏斑马鱼中多巴胺的合成和运输,从而破坏正常的神经发育,从而影响多巴胺能信号传导。根据实验结果,
更新日期:2017-01-31
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