Fluoride activates microglia, secretes inflammatory factors and influences synaptic neuron plasticity in the hippocampus of rats

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.