Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China; Aquacultural Engineering R&D Center, School of Marine Technology and Environment Institute, Dalian Ocean University, Dalian, 116023, Liaoning, China.
Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China.
Toxicology. 2019 Jan 15;412:55-62. doi: 10.1016/j.tox.2018.11.015. Epub 2018 Nov 30.
Both animal study and epidemiological survey revealed the associations between defects of cognitive function and the developmental exposure to perfluorooctane sulfonate (PFOS), while the mechanism is not well known. The SD rats were exposed PFOS at 1.7, 5 and 15 mg/L by drinking water from gestation to the adulthood of the pups for evaluating the effects of PFOS exposure on long-term potentiation (LTP) and the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors trafficking. Whole-life exposure of PFOS beginning in utero to adulthood significantly inhibited the induction and expression of LTP, and the input/output curve (I/O) and paired-pulse facilitation (PPF) were moderately suppressed, suggesting that PFOS might affect the synaptic transmission and plasticity both in pre- and post-synaptic cells. Meanwhile, PFOS decreased the mRNA levels of AMPA receptor subunits GluA1 and GluA2, and the protein amounts in the membrane, with the total GluA1 and GluA2 protein amounts increased, indicating the internalization of AMPA receptors. Furthermore, tests in the primary hippocampal neurons also support the decreased mRNA levels of GluA1 and GluA2 induced by PFOS. After the pretreatment of AMPA antagonist (NBQX), PFOS decreased the expression of GluA1 and GluA2 and increased internal cellular calcium at much lower levels than that in the neurons without NBQX treatment. The results provide electrophysiological evidence for the impaired cognitive function induced by PFOS exposure and revealed the critical role of AMPA receptor involved.
动物研究和流行病学调查都揭示了认知功能缺陷与全氟辛烷磺酸（PFOS）发育暴露之间的关联，而其机制尚不清楚。通过饮用含 1.7、5 和 15mg/L PFOS 的水，SD 大鼠从妊娠期到幼仔成年期持续暴露于 PFOS 中，以评估 PFOS 暴露对长时程增强（LTP）的影响，以及α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体运输的作用。从胚胎期到成年期的全生命周期 PFOS 暴露显著抑制了 LTP 的诱导和表达，输入/输出曲线（I/O）和成对脉冲易化（PPF）也受到中度抑制，这表明 PFOS 可能影响突触传递和可塑性。同时，PFOS 降低了 AMPA 受体亚基 GluA1 和 GluA2 的 mRNA 水平，以及膜中的蛋白含量，总 GluA1 和 GluA2 蛋白含量增加，表明 AMPA 受体内化。此外，原代海马神经元的测试也支持 PFOS 引起的 GluA1 和 GluA2 mRNA 水平降低。在 AMPA 拮抗剂（NBQX）预处理后，PFOS 在比没有 NBQX 处理的神经元低得多的水平下降低了 GluA1 和 GluA2 的表达，并增加了细胞内钙。这些结果为 PFOS 暴露引起的认知功能障碍提供了电生理学证据，并揭示了 AMPA 受体参与的关键作用。
