Single and mixture per- and polyfluoroalkyl substances accumulate in developing Northern leopard frog brains and produce complex neurotransmission alterations
Single and mixture per- and polyfluoroalkyl substances accumulate in developing Northern leopard frog brains and produce complex neurotransmission alterations
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DOI：
10.1016/j.ntt.2020.106907
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发表时间：
2020-09-01
影响因子：
2.9
通讯作者：
Cannon, J. R.
中科院分区：
文献类型：
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作者：
Foguth, R. M.;Hoskins, T. D.;Cannon, J. R.
全氟烷基和多氟烷基物质(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，人们对它们对发育中的大脑的影响知之甚少。为了确定全氟辛烷磺酸对大脑和心脏神经支配的影响，我们进行了一项室外中膜实验，北方豹蛙幼虫暴露在对照组、10 ppb全氟辛烷磺酸(PFOS)或总计10 ppb的PFAS混合物中，这些混合物模仿形成受泡沫影响的地表水的水膜(4 ppb全氟辛烷磺酸、3 ppb全氟己烷磺酸、1.25 ppb全氟辛酸盐、1.25 ppb全氟己酸盐和0.5 ppb全氟辛酸酯)。在水中加入PFAS和25条幼虫(Gosner期(GS)25)，每个处理(n=4个)。30天后，每个中胚层收获8个大脑，剩余的幼虫发育到GS 46(即变态)，然后收集大脑和心脏。记录体重、长度、GS和变态时间。用LC/MS/MS法定量5种PFA的脑内浓度，用高效液相色谱-电化学检测法测定5-羟色胺及其代谢物去甲肾上腺素、γ-氨基丁酸和谷氨酸的含量，用Invitgen Amplex Red乙酰胆碱法测定乙酰胆碱和乙酰胆碱酯酶的活性。全氟辛烷磺酸在大脑中以时间和剂量依赖的方式积累。30天后，混合物降低了5-羟色胺，而两种PFAS处理都降低了谷氨酸。有趣的是，在GS 46的PFAS治疗中，乙酰胆碱增加。这项研究表明，与发育环境相关的PFAS暴露会改变神经递质，特别是乙酰胆碱。
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-npentanoate). 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, y-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 neuro-transmitters, especially acetylcholine.