Lee Hyojin, Tran Cong M, Jeong Soomin, Kim Seong Soon, Bae Myung Ae, Kim Ki-Tae
Department of Environmental Engineering, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea; Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
Department of Environmental Energy Engineering, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea.
Neurotoxicology. 2022 Dec;93:257-264. doi: 10.1016/j.neuro.2022.10.007. Epub 2022 Oct 13.
While the developmental neurotoxicity of perfluorooctane sulfonate (PFOS) has been reported, its seizurogenic potential has not been investigated. Behavior assessment was conducted in zebrafish larvae exposed to PFOS at concentrations of 0, 0.1, 1, 5, 10, and 20 μM. Changes in electrophysiological signals and in the concentration of 20 neurochemicals were measured. Behavior assessment revealed that PFOS altered larval behaviors and significantly increased the counts and duration of bursting (an irregular high-speed movement). Electrophysiological analysis showed that the number of seizure-like events and duration of seizure-like signals were significantly increased, corresponding to results observed using pentylenetetrazol as a positive seizurogenic agent. The outbreak of seizures detected via abnormal electrophysiological signals was confirmed by the increased expression of c-fos and bdnf, which are typical seizure-related genes. Analysis of neurochemicals indicated that PFOS dysregulated overall neurotransmission systems, and aberrant endogenous concentrations of various neurochemicals in the amino acid, cholinergic, dopaminergic, serotonergic and kynurenergic, and GABAergic systems were associated with seizure-like behavior and signals. This study, the first to demonstrate that exposure to PFOS provokes a seizurogenic effect in developing zebrafish larvae, should stimulate further research on the association between PFOS exposure and neurodevelopmental toxicity or neurological disorders.
虽然全氟辛烷磺酸（PFOS）的发育神经毒性已有报道，但其致癫痫潜力尚未得到研究。对暴露于浓度为0、0.1、1、5、10和20 μM的PFOS的斑马鱼幼体进行了行为评估。测量了电生理信号和20种神经化学物质浓度的变化。行为评估显示，PFOS改变了幼体行为，并显著增加了爆发（一种不规则的高速运动）的次数和持续时间。电生理分析表明，癫痫样事件的数量和癫痫样信号的持续时间显著增加，这与使用戊四氮作为阳性致癫痫剂所观察到的结果一致。通过异常电生理信号检测到的癫痫发作通过典型的癫痫相关基因c-fos和bdnf表达的增加得到证实。神经化学物质分析表明PFOS使整体神经传递系统失调，氨基酸、胆碱能、多巴胺能、5-羟色胺能、犬尿氨酸能和γ-氨基丁酸能系统中各种神经化学物质异常的内源性浓度与癫痫样行为和信号有关。本研究首次证明暴露于PFOS会在发育中的斑马鱼幼体中引发致癫痫作用，并应激发对PFOS暴露与神经发育毒性或神经疾病之间关联的进一步研究。
