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Single and mixture per- and polyfluoroalkyl substances accumulate in developing Northern leopard frog brains and produce complex neurotransmission alterations.
Neurotoxicology and Teratology ( IF 2.6 ) Pub Date : 2020-06-17 , DOI: 10.1016/j.ntt.2020.106907
R M Foguth 1 , T D Hoskins 2 , G C Clark 3 , M Nelson 4 , R W Flynn 2 , C de Perre 5 , J T Hoverman 2 , L S Lee 5 , M S Sepúlveda 2 , J R Cannon 1
Affiliation  

Per- and polyfluoroalkyl substances (PFAS) are present in water and >99% of human serum. They are found in brains of wildlife; however, little is known about effects on the developing brain. To determine the effects of PFAS on brain and cardiac innervation, we conducted an outdoor mesocosm experiment with Northern leopard frog larvae (Rana pipiens) exposed to control, 10 ppb perfluorooctane sulfonate (PFOS), or a PFAS mixture totaling 10 ppb that mimicked aqueous film forming foam-impacted surface water (4 ppb PFOS, 3 ppb perfluorohexane sulfonate, 1.25 ppb perfluorooctanoate, 1.25 ppb perfluorohexanoate, and 0.5 ppb perfluoro-n-pentanoate). Water was spiked with PFAS and 25 larvae (Gosner stage (GS) 25) added to each mesocosm (n = 4 mesocosms per treatment). After 30 days, we harvested eight brains per mesocosm and remaining larvae developed to GS 46 (i.e. metamorphosis) before brains and hearts were collected. Weight, length, GS, and time to metamorphosis were recorded. Brain concentrations of all five PFAS were quantified using LC/MS/MS. Dopamine and metabolites, serotonin and its metabolite, norepinephrine, γ-aminobutyric acid, and glutamate were quantified using High Performance Liquid Chromatography with electrochemical detection while acetylcholine and acetylcholinesterase activity were quantified with the Invitrogen Amplex Red Acetylcholine Assay. PFOS accumulated in the brain time- and dose-dependently. After 30 days, the mixture decreased serotonin while both PFAS treatments decreased glutamate. Interestingly, acetylcholine increased in PFAS treatments at GS 46. This research shows that developmental environmentally relevant exposure to PFAS changes neurotransmitters, especially acetylcholine.



中文翻译:

单一和混合的全氟和多氟烷基物质在发育中的北豹蛙大脑中积累,并产生复杂的神经传递改变。

全氟和多氟烷基物质 (PFAS) 存在于水和 > 99% 的人血清中。它们存在于野生动物的大脑中;然而,对发育中的大脑的影响知之甚少。为了确定 PFAS 对大脑和心脏神经支配的影响,我们对暴露于对照、10 ppb 全氟辛烷磺酸 (PFOS) 或总计 10 ppb 模拟水膜的 PFAS 混合物的北豹蛙幼虫 ( Rana pipiens )进行了户外中胚层实验形成受泡沫影响的地表水(4 ppb PFOS、3 ppb 全氟己烷磺酸盐、1.25 ppb 全氟辛酸盐、1.25 ppb 全氟己酸盐和 0.5 ppb 全氟正戊酸盐)。水中掺入 PFAS 和 25 只幼虫(Gosner 阶段 (GS) 25)添加到每个中层(n = 每次治疗 4 个中胚层)。30 天后,我们在每个中胚层收获了 8 个大脑,在收集大脑和心脏之前,剩余的幼虫发育到 GS 46(即变态)。记录体重、身长、GS 和变态时间。使用 LC/MS/MS 对所有五种 PFAS 的脑浓度进行量化。多巴胺和代谢物、5-羟色胺及其代谢物、去甲肾上腺素、γ-氨基丁酸和谷氨酸盐使用高效液相色谱和电化学检测进行定量,而乙酰胆碱和乙酰胆碱酯酶活性使用 Invitrogen Amplex 红色乙酰胆碱检测进行定量。全氟辛烷磺酸以时间和剂量依赖性方式在大脑中积累。30 天后,混合物降低了血清素,而两种 PFAS 处理都降低了谷氨酸盐。有趣的是,在 GS 46 的 PFAS 治疗中乙酰胆碱增加。

更新日期:2020-07-02
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