The effects of fluoride on neuronal function occurs via cytoskeleton damage and decreased signal transmission
The effects of fluoride on neuronal function occurs via cytoskeleton damage and decreased signal transmission
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氟化物对神经元功能的影响是通过细胞骨架损伤和信号传输减少而发生的。
DOI：
10.1016/j.chemosphere.2017.06.128
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发表时间：
2017-10-01
期刊：
影响因子：
8.8
通讯作者：
Wang, Wenkui
中科院分区：
文献类型：
--
作者：
Chen, Lingli;Ning, Hongmei;Wang, Wenkui
据报道，氟化物暴露可能导致严重的公共卫生问题，特别是神经毒性。然而，其潜在机制仍不清楚。本研究以神经细胞Neuro-2A为研究对象，探讨氟对神经细胞骨架的影响。将Neuro-2A细胞暴露于0、1、2、4和6 mM氟化钠（NaF）24 h。检测细胞活力和乳酸脱氢酶（LDH）释放。观察到暴露于NaF降低了细胞活力，破坏了细胞膜完整性，并释放了高水平的LDH。观察到的变化以剂量反应方式发生。形态学观察显示，细胞变圆，并松散粘附暴露于氟化钠。高剂量氟化钠治疗后轴突棘和正常特征消失。MAP 2和突触素的表达降低，特别是在4 mM和6 mM的MAP 2（P < 0.05）。这些结果证实了形态学观察结果。采用ELISA和Western-blot方法检测谷氨酸和谷氨酸受体（NMDAR）蛋白的含量，以帮助了解突触与神经递质释放之间的关系。与对照组相比，4 mM和6 mM组谷氨酸和NMDAR表达显著下降（P < 0.05）。最后，观察到的超微结构的变化与剂量的氟化钠：突触消失，线粒体凝集，空泡形成，和细胞水肿。两者合计，氟化钠暴露破坏细胞的完整性和抑制神经递质的释放，从而影响神经元功能。这些发现提供了更深入的了解氟化钠在神经元损伤中的作用，这可能有助于更好地理解氟化物诱导的神经毒性。(C)2017爱思唯尔有限公司版权所有。
It has been reported that fluoride exposure may cause serious public health problems, particularly neurotoxicity. However, the underlying mechanisms remain unclear. This study used Neuro-2A cells to investigate the effects of fluoride on the cytoskeleton. The Neuro-2A cells were exposed to 0, 1, 2, 4 and 6 mM sodium fluoride (NaF) for 24 h. Cell viability and lactate dehydrogenase (LDH) release were examined. It was observed that exposure to NaF reduced cell viability, disrupted cellular membrane integrity, and high levels of LDH were released. The observed changes occurred in a dose response manner. Morphologic observations showed that cell became rounded and were loosely adherent following exposure to NaF. Axon spines and normal features disappeared with high dose NaF treatment. The expression of MAP2 and synaptophysin decreased, particularly at 4 mM and 6 mM (P < 0.05) for MAP2. These results corroborate the morphologic observations. The content of glutamate and NMDAR (glutamate receptor) protein were assessed to help understand the relationship between synapses and neurotransmitter release using ELISA and Western-blot. Compared with the control, glutamate and NMDAR expression declined significantly at 4 mM and 6 mM (P < 0.05) group. Finally, the ultrastructural changes observed with increasing doses of NaF were: disappearance of synapses, mitochondrial agglutination, vacuole formation, and cellular edema. Taken together, NaF exposure disrupted cellular integrity and suppressed the release of neurotransmitters, thus effecting neuronal function. These findings provide deeper insights into roles of NaF in neuron damage, which could contribute to a better understanding of fluoride-induced neurotoxicity. (C) 2017 Elsevier Ltd. All rights reserved.