BACKGROUND 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. METHODS Zebrafish embryos were exposed to the following individual treatments; 0.1% DMSO (vehicle control); 0.3μM CPF; 0.01, 0.03, 0.1, 0.3μM BDE-47; 0.003, 0.03, 0.3, 1, 3, 10, 20μM BDE-99 from 5 until 120h 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. RESULTS In the short-term, larval locomotor activity was reduced in larvae treated with 0.3μM CPF and 0.1μM BDE-47. BDE-99 treatment caused non-monotonic dose effects, with 0.3μM causing hyperactivity and 1μM 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. DISCUSSION 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.

中文翻译：

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发育中暴露于低浓度的两种溴化阻燃剂BDE-47和BDE-99，会导致斑马鱼的终生行为改变。

背景技术直到2000年代初，多溴二苯醚（PBDEs）被广泛用作阻燃剂，主要用于家具和电子产品中。多溴二苯醚在环境中的持续存在导致普遍存在的低水平暴露，婴儿和儿童的暴露量高于成人。越来越多的证据表明，生命早期的低水平接触会影响大脑发育并导致长期的行为障碍。我们研究了斑马鱼暴露于低剂量的两种主要多溴二苯醚中的影响。2,2'，4,4'，5，-五溴二苯醚（BDE-99）和2,2'，4,4'，-四溴二苯醚（BDE-47），在短时和长时胚胎发育过程中术语行为终点。我们包括了有机磷酸盐农药毒死rif（CPF），因为它对从斑马鱼到人类的各种物种具有良好的神经毒性。方法将斑马鱼的胚胎进行以下单独处理；0.1％DMSO（车辆控制）; 0.3μMCPF; 0.01、0.03、0.1、0.3μM BDE-47；受精后5至120h（hpf）为0.003、0.03、0.3、1、3、10、20μM BDE-99。确定低暴露水平为不会立即引起明显毒性的暴露水平，并在低水平范围内进行行为分析。在144hpf下测试幼虫的运动活性。在大约6个月大的时候，成年斑马鱼在行为电池组中进行了测试，包括与焦虑相关的行为，感觉运动反应和习惯，社交互动以及避免捕食动物的测定。结果在短期内，用0.3μMCPF和0.1μMBDE-47处理的幼虫幼虫运动能力降低。BDE-99治疗引起非单调剂量效应，其中0.3μM引起机能亢进，而1μM或更高则引起机能减退。从长期来看，在所有治疗中，与成人焦虑相关的行为均在新颖的油箱潜水测试和轻击测试中得到了降低。讨论我们显示，斑马鱼胚胎暴露于低浓度的溴化阻燃剂BDE-47和BDE-99以及有机磷酸盐农药CPF中，会造成短期和长期的行为损害。有趣的是，我们还发现，在极低的暴露浓度下，对幼虫活动没有可见的影响，成年行为仍然受到严重影响。3μM引起机能亢进，1μM或更高引起机能减退。从长期来看，通过新型油罐潜水试验和轻击试验均可以降低成人焦虑相关行为。讨论我们表明，斑马鱼胚胎暴露于低浓度的溴化阻燃剂BDE-47和BDE-99以及有机磷酸盐农药CPF中，会造成短期和长期的行为损害。有趣的是，我们还发现，在极低的暴露浓度下，对幼虫活动没有可见的影响，成年行为仍然受到严重影响。3μM引起机能亢进，1μM或更高引起机能减退。从长期来看，通过新型的油箱潜水测试和轻击测试均可以降低所有治疗中成人焦虑相关的行为。讨论我们显示，斑马鱼胚胎暴露于低浓度的溴化阻燃剂BDE-47和BDE-99以及有机磷酸盐农药CPF中，会造成短期和长期的行为损害。有趣的是，我们还发现，在极低的暴露浓度下，对幼虫活动没有可见的影响，成年行为仍然受到严重影响。讨论我们显示，斑马鱼胚胎暴露于低浓度的溴化阻燃剂BDE-47和BDE-99以及有机磷酸盐农药CPF中，会造成短期和长期的行为损害。有趣的是，我们还发现，在极低的暴露浓度下，对幼虫活动没有可见的影响，成年行为仍然受到严重影响。讨论我们显示，斑马鱼胚胎暴露于低浓度的溴化阻燃剂BDE-47和BDE-99以及有机磷酸盐农药CPF中，会造成短期和长期的行为损害。有趣的是，我们还发现，在极低的暴露浓度下，对幼虫活动没有可见的影响，成年行为仍然受到严重影响。