Effect of chronic F- exposure on ionotropic glutamate AMPA and NMDA receptors in rat hippocampus

Abstract

Our previous study has shown that long-term consumption of excessive fluoride (F−) impaired spatial learning and formation of long-term memory of Wistar rats. The present study examined alterations in expression of a few subunits composing glutamate AMPA and NMDA receptors in hippocampal cells in response to F− poisoning at transcriptional and translational levels, as well as their subcellular distribution and phosphorylation state. The rats were given water with background 0.4 (control), 5, 20 and 50 ppm F− (as NaF) for 12 months. The expression of Gria1, Gria2 and Gria3 genes remained stable in the hippocampal tissues of F−-exposed animals. However, long-term F− intake resulted in translocation of GluA2 subunits of AMPA receptors from membranes to cytosol and opposite trafficking of GluA3 subunits, whereas subcellular distribution of GluA1 subunits was unaltered. These changes were accompanied by increased phosphorylation of GluA1 and GluA2 subunits in cytosol and/or membranes. The expression of Grin1 gene and GluN1 subunits of NMDARs were comparable in hippocampal cells of rats from all groups. In contrast, F− poisoning was accompanied by a rise in both Grin2a and Grin2b mRNA content and enhanced levels of total and phosphorylated forms of GluN2A and GluN2B subunits in/or cytosol and membranes. Such changes indicate the predominance of Ca2+-permeable AMPARs and altered ratio between different types of NMDARs subunits at membranes of hippocampal cells of F−-exposed rats, which may underly the disturbances in cognitive capacities of animals.