Liao Chun-Yang, Li Xiang-Yao, Wu Bei, Duan Shumin, Jiang Gui-Bin
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Environ Sci Technol. 2008 Jul 15;42(14):5335-41. doi: 10.1021/es800018k.
Perfluorooctane sulfonate (PFOS) is a persistent and bioaccumulative pollutant ubiquitous in wildlife and humans. Although the distribution and fate of PFOS have been widely studied, its potential neurotoxicity remains largely unknown. In the present study, the acute and chronic effects of PFOS on the development and synaptic transmission of hippocampal neurons was examined. Perfusion with PFOS markedly increased the frequency of miniature postsynaptic currents (mPSCs) and slightly elevated the amplitude of mPSCs in cultured hippocampal neurons. Perfusion with PFOS also increased the amplitude of field excitatory postsynaptic potentials (fEPSPs) recorded in the CA1 region of hippocampal slices. Both of these effects were largely blocked by the L-type Ca2+ channel antagonist nifedipine. Further studies showed that PFOS enhanced inward Ca2+ currents and increased intracellular Ca2+ in cultured neurons; these effects were also substantially inhibited by nifedipine. Moreover, prolonged treatment with PFOS moderately inhibited neurite growth and dramatically suppressed synaptogenesis in cultured neurons in a nifedipine-sensitive manner. Thus, through enhancement of Ca2+ channels, PFOS may exhibit both acute excitotoxic effects on synaptic function and chronically inhibit synaptogenesis in the brain.
全氟辛烷磺酸（PFOS）是一种在野生动物和人类中普遍存在的持久性生物累积性污染物。尽管对PFOS的分布和归宿已进行了广泛研究，但其潜在的神经毒性在很大程度上仍不清楚。在本研究中，检测了PFOS对海马神经元发育和突触传递的急性和慢性影响。用PFOS灌注可显著增加培养的海马神经元中微小突触后电流（mPSCs）的频率，并轻微提高mPSCs的幅度。用PFOS灌注还可增加海马脑片CA1区记录的场兴奋性突触后电位（fEPSPs）的幅度。这两种效应在很大程度上均被L型Ca2+通道拮抗剂硝苯地平所阻断。进一步研究表明，PFOS增强了培养神经元中的内向Ca2+电流并增加了细胞内Ca2+；这些效应也被硝苯地平显著抑制。此外，PFOS的长期处理以硝苯地平敏感的方式适度抑制了培养神经元中的神经突生长并显著抑制了突触形成。因此，通过增强Ca2+通道，PFOS可能对突触功能表现出急性兴奋毒性作用，并长期抑制大脑中的突触形成。
