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.

流行病学研究报告说，高氟化饮用水可能会显着降低接触儿童的智商（IQ）。据认为，突触可塑性是发展儿童的学习和记忆技能的基础。但是，激活的小胶质细胞经氟化物处理对突触可塑性的影响尚不清楚。我们以前的研究表明，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，在亚慢性饮水的大鼠模型中评估了海马依赖性记忆状态。使用免疫荧光染色检查海马中的小胶质细胞活化，并检测突触素（SYP）和突触后密度蛋白95（PSD-95）的表达，暴露大鼠的d-天冬氨酸（NMDA）受体亚单位NMDAR2β。我们发现氟化物暴露激活了小胶质细胞并增加了DAP12和TREM2的表达，并通过ERK / MAPK和P38 / MAPK信号途径促进了促炎性细胞因子的分泌。此外，氟化物抑制LTP并降低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。