Department of Environmental and Occupational Health, Liaoning Provincial Key Laboratory of Arsenic Biological Effect and Poisoning, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, PR China.
Neurotoxicology. 2018 Dec;69:108-120. doi: 10.1016/j.neuro.2018.09.006. Epub 2018 Sep 28.
Epidemiological studies have reported that highly fluoridated drinking water may significantly decrease the Intelligence Quotient (IQ) of exposed children. It is thought that synaptic plasticity is the basis of learning and memory skills in developing children. However, the effect on synaptic plasticity by activated microglia induced via fluoride treatment is less clear. Our previous research showed that fluoride ions activated microglia which then released pro-inflammatory cytokines. In this study, hippocampal-dependent memory status was evaluated in rat models sub-chronically exposed to fluoride in their drinking water. Microglial activation in the hippocampus was examined using immunofluorescence staining and the expression of synaptophysin (SYP) and postsynaptic density protein 95 (PSD-95), Long-term potentiation (LTP) and the expression of Amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) receptor subunit GluR2 as well as N-methyl-d-aspartate (NMDA) receptor subunit NMDAR2β of exposed rats. We found that fluoride exposure activated microglia and increased the expression of DAP12 and TREM2, as well as promoted pro-inflammatory cytokines secretion via ERK/MAPK and P38/MAPK signal pathways. Furthermore fluoride depressed LTP and decreased PSD-95 protein levels as well as expression of ionotropic glutamate receptors GluR2 and NMDAR2β. We concluded that the role of fluoride on synaptic plasticity may be associated with neuroinflammation induced by microglia.
流行病学研究报告称，高氟饮用水可能会显著降低暴露于水中的儿童的智商。人们认为，突触可塑性是发育中儿童学习和记忆技能的基础。然而，氟化物处理激活小胶质细胞对突触可塑性的影响尚不清楚。我们之前的研究表明，氟离子激活小胶质细胞，然后释放促炎细胞因子。在这项研究中，我们通过评估在饮用水中接受亚慢性氟暴露的大鼠模型中海马依赖型记忆状态，来研究氟化物对突触可塑性的影响。通过免疫荧光染色检查海马中的小胶质细胞激活情况，以及突触小体相关蛋白（SYP）和突触后密度蛋白 95（PSD-95）的表达、长时程增强（LTP）以及 Amino-3-hydroxy-5-methy-4-isoxazole propionate（AMPA）受体亚基 GluR2 和 N-甲基-D-天冬氨酸（NMDA）受体亚基 NMDAR2β的表达。我们发现，氟化物暴露激活了小胶质细胞，增加了 DAP12 和 TREM2 的表达，并通过 ERK/MAPK 和 P38/MAPK 信号通路促进了促炎细胞因子的分泌。此外，氟化物还抑制了 LTP，降低了 PSD-95 蛋白水平以及离子型谷氨酸受体 GluR2 和 NMDAR2β的表达。我们得出结论，氟化物对突触可塑性的作用可能与小胶质细胞引起的神经炎症有关。
