Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of aCaMKII/NR2A synaptic complex and phosphorylated GluR1-containing AMPA receptor cascades

Background: N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propinoic acid (AMPA) receptors bound to postsynaptic density-95(PSD-95) and a isoform of calcium/calmodulin-dependent protein kinase II(aCaMKII) is fundamentally involved in the regulation of working memory. Theaim of present study was to investigate the alterations of NMDA and AMPAreceptors responsible for hippocampal synaptic dysfunction and selective neuronalcell death after chronic renal failure (CRF) which may be associated with impairmentof working memory. Methods: Altered interactions between NMDA and AMPA receptors and PSD-95and aCaMKII were analyzed in the cornu ammonis (CA) 1 and CA3/dentate gyrus(DG) subfields of the uremic rat hippocampi using the immunoblotting andimmunoprecipitation methods. Results: Uremia induced by CRF produced necrotic cell death and decreasedneuronal nucleoli protein levels in the hippocampal CA1 subfield, but not in theCA3/DG subfields. The CA1 subfields of CRF rats exhibited significant decreasesand increases, respectively, in the expressions of PSD-95/NR2B and aCaMKII/NR2A synaptic complex. Moreover, increased phosphorylation of glutamatereceptor type 1 (GluR1) AMPA receptor at ser831 was observed in the CA1subfield after CRF. Conclusion: These hippocampal CA1 neuronal vulnerability may be responsiblefor memory dysfunction after CRF as mediated by an increase in NR2AcontainingNMDA receptors bound to aCaMKII and subsequent activation ofGluR1-containing AMPA receptors caused by the phosphorylation of GluR1 atser831.