Primary cultures of cerebellar granule neurons (CGNs) derived from chicken embryos were used to explore the effects on developmental neurotoxicity by a complex defined mixture of persistent organic pollutants (POPs). Its chemical composition and concentrations were based on blood levels in the Norwegian/Scandinavian population. Perfluorooctane sulfonic acid (PFOS) alone, its most abundant compound was also evaluated. Different stages of CGNs maturation, between day in vitro (DIV) 1, 3, and 5 were exposed to the POP mixture, or PFOS alone. Their combination with glutamate, an excitatory endogenous neurotransmitter important in neurodevelopment, also known to cause excitotoxicity was evaluated. Outcomes with the mixture at 500x blood levels were compared to PFOS at its corresponding concentration of 20 μM. The POP mixture reduced tetrazolium salt (MTT) conversion at earlier stages of maturation, compared to PFOS alone. Glutamate-induced excitotoxicity was enhanced above the level of that induced by glutamate alone, especially in mature CGNs at DIV5. Glutathione (GSH) concentrations seemed to set the level of sensitivity for the toxic insults from exposures to the pollutants. The role of N-methyl-D-aspartate receptor (NMDA-R) mediated calcium influx in pollutant exposures was investigated using the non-competitive and competitive receptor antagonists MK-801 and CGP 39551. Observations indicate a calcium-independent, but still NMDA-R dependent mechanism in the absence of glutamate, and a calcium- and NMDA-R dependent one in the presence of glutamate. The outcomes for the POP mixture cannot be explained by PFOS alone, indicating that other chemicals in the mixture contribute its overall effect.

来自鸡胚胎的小脑颗粒神经元 (CGN) 的原代培养物用于探索持久性有机污染物 (POPs) 的复杂定义混合物对发育神经毒性的影响。其化学成分和浓度基于挪威/斯堪的纳维亚人口的血液水平。还评估了单独的全氟辛烷磺酸 (PFOS)，其含量最高的化合物。CGNs 成熟的不同阶段，在体外一天之间(DIV) 1、3 和 5 暴露于持久性有机污染物混合物或单独的全氟辛烷磺酸中。评估了它们与谷氨酸盐的组合，谷氨酸盐是一种在神经发育中很重要的兴奋性内源性神经递质，也已知会引起兴奋性毒性。将 500 倍血液浓度的混合物的结果与其相应浓度 20 μM 的 PFOS 进行比较。与单独的全氟辛烷磺酸相比，持久性有机污染物混合物在成熟的早期阶段降低了四唑盐 (MTT) 的转化率。谷氨酸诱导的兴奋性毒性增强高于单独谷氨酸诱导的水平，尤其是在 DIV5 的成熟 CGN 中。谷胱甘肽 (GSH) 浓度似乎决定了对暴露于污染物的毒性损害的敏感度水平。使用非竞争性和竞争性受体拮抗剂 MK-801 和 CGP 39551 研究了 N-甲基-D-天冬氨酸受体 (NMDA-R) 介导的钙流入在污染物暴露中的作用。观察表明钙独立，但仍然是 NMDA -R 依赖机制在不存在谷氨酸的情况下，以及钙和 NMDA-R 依赖机制在谷氨酸存在的情况下。持久性有机污染物混合物的结果不能仅用全氟辛烷磺酸来解释，这表明混合物中的其他化学物质对其整体影响有贡献。