Developmental exposure to low concentrations of two brominated flame retardants, BDE-47 and BDE-99, causes life-long behavioral alterations in zebrafish.

Developmental exposure to low concentrations of two brominated flame retardants, BDE-47 and BDE-99, causes life-long behavioral alterations in zebrafish.
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DOI:
10.1016/j.neuro.2017.09.007
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发表时间:
2018-05
期刊:
影响因子:
3.4
通讯作者:
Levin ED
Levin ED
中科院分区:
医学3区
文献类型:
--
作者:
Glazer L;Wells CN;Drastal M;Odamah KA;Galat RE;Behl M;Levin ED

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直到2000年代初,多溴联苯醚(PBDE)还被广泛用作阻燃剂,主要用于家居用品和电子产品中。多溴联苯醚在环境中的持久性导致人们继续普遍接触低水平的多溴联苯醚,婴儿和儿童的接触量高于成人。越来越多的证据表明,生命早期阶段的低水平暴露会影响大脑发育,并导致长期行为障碍。我们研究了斑马鱼在胚胎发育过程中暴露于低剂量的两种主要多溴二苯醚(2,2 ',4,4',5,-五溴二苯醚(BDE-99)和2,2 ',4,4',-四溴二苯醚(BDE-47))对短期和长期行为终点的影响。我们包括有机磷农药毒死蜱(CPF),因为它在从斑马鱼到人类的物种中具有良好的神经毒性。斑马鱼胚胎在受精后5至120小时(hpf)暴露于以下单独处理:0.1% DMSO(溶剂对照); 0.3 µM CPF; 0.01、0.03、0.1、0.3 µM BDE-47; 0.003、0.03、0.3、1、3、10、20 µM BDE-99。低接触水平被确定为不会引起直接明显毒性的水平,并在低水平范围内进行行为测定。在144 hpf下,测试幼虫的运动活性。在大约6个月大时,成年斑马鱼在行为电池中进行测试,包括焦虑相关行为、感觉运动反应和习惯化、社会互动和捕食者回避的测定。在短期内,用0.3 µM CPF和0.1 µM BDE-47处理的幼虫的运动活动减少。BDE-99处理引起非单调的剂量效应,0.3 μM引起活动过度,1 μM或更高引起活动减退。从长期来看,在所有治疗中,成人焦虑相关行为都有所减少,这在新的坦克潜水试验和自来水试验中都有体现。我们发现,斑马鱼胚胎暴露于低浓度的溴化阻燃剂BDE-47和BDE-99,以及有机磷农药CPF,导致短期和长期的行为障碍。有趣的是,我们还发现,在非常低的暴露浓度下,对幼虫的活动没有明显的影响,成虫的行为仍然受到强烈的影响。
Polybrominated diphenyl ethers (PBDEs) were widely used as flame retardants until the early 2000s, mainly in home furnishings and electronics. The persistence of PBDEs in the environment leads to continued ubiquitous exposure to low levels, with infants and children experiencing higher exposures than adults. Accumulating evidence suggest that low-level exposures during early life stages can affect brain development and lead to long-term behavioral impairments. We investigated the effects of zebrafish exposure to low doses of the two prominent PBDEs; 2,2',4,4',5,-Pentabromodiphenyl ether (BDE-99) and 2,2',4,4',-Tetrabromodiphenyl ether (BDE-47), during embryo-development on short- and long-term behavioral endpoints. We included the organophosphate pesticide chlorpyrifos (CPF) due to its well documented neurotoxicity across species from zebrafish to humans. Zebrafish embryos were exposed to the following individual treatments; 0.1% DMSO (vehicle control); 0.3 µM CPF; 0.01, 0.03, 0.1, 0.3 µM BDE-47; 0.003, 0.03, 0.3, 1, 3, 10, 20 µM BDE-99 from 5 until 120 hours post fertilization (hpf). Low exposure levels were determined as those not causing immediate overt toxicity, and behavior assays were conducted in the low-level range. At 144 hpf the larvae were tested for locomotor activity. At approximately 6 months of age adult zebrafish were tested in a behavioral battery including assays for anxiety-related behavior, sensorimotor response and habituation, social interaction, and predator avoidance. In the short-term, larval locomotor activity was reduced in larvae treated with 0.3 µM CPF and 0.1 µM BDE-47. BDE-99 treatment caused non-monotonic dose effects, with 0.3 µM causing hyperactivity and 1 µM or higher causing hypoactivity. In the long-term, adult anxiety-related behavior was reduced in all treatments as measured in both the novel tank dive test and tap test. We show that exposure of zebrafish embryos to low concentrations of the brominated flame retardants BDE-47 and BDE-99, and the organophosphate pesticide CPF, caused both short- and long-term behavioral impairments. Interestingly, we also found that at very low exposure concentrations, where there were no visible effects on larval activity, adult behavior was still strongly affected.
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