title: Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of αCaMKII/NR2A synaptic complex and phosphorylated GluR1-containing AMPA receptor cascades.
abstract: 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 α isoform of calcium/calmodulin-dependent protein kinase II (αCaMKII) is fundamentally involved in the regulation of working memory. The aim of present study was to investigate the alterations of NMDA and AMPA receptors responsible for hippocampal synaptic dysfunction and selective neuronal cell death after chronic renal failure (CRF) which may be associated with impairment of working memory.
  
  
  METHODS
  Altered interactions between NMDA and AMPA receptors and PSD-95 and αCaMKII were analyzed in the cornu ammonis (CA) 1 and CA3/dentate gyrus (DG) subfields of the uremic rat hippocampi using the immunoblotting and immunoprecipitation methods.
  
  
  RESULTS
  Uremia induced by CRF produced necrotic cell death and decreased neuronal nucleoli protein levels in the hippocampal CA1 subfield, but not in the CA3/DG subfields. The CA1 subfields of CRF rats exhibited significant decreases and increases, respectively, in the expressions of PSD-95/NR2B and αCaMKII/NR2A synaptic complex. Moreover, increased phosphorylation of glutamate receptor type 1 (GluR1) AMPA receptor at ser831 was observed in the CA1 subfield after CRF.
  
  
  CONCLUSIONS
  These hippocampal CA1 neuronal vulnerability may be responsible for memory dysfunction after CRF as mediated by an increase in NR2A-containing NMDA receptors bound to αCaMKII and subsequent activation of GluR1-containing AMPA receptors caused by the phosphorylation of GluR1 at ser831.
authors.affiliation: Section of Neuroscience Research, Medical Institute of Dongguk University, Gyeongju, Korea; Department of Anatomy, College of Medicine, Dongguk University, Gyeongju, Korea.
authors.forename: Jong Wan
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Dongguk University, Gyeongju, Korea.
authors.forename: Gyoung Yim
authors.initials: GY
authors.lastname: Ha
authors.affiliation: Section of Neuroscience Research, Medical Institute of Dongguk University, Gyeongju, Korea; Department of Anatomy, College of Medicine, Dongguk University, Gyeongju, Korea.
authors.forename: Yong Wook
authors.initials: YW
authors.lastname: Jung
keywords: Alpha-amino-3-hydroxy-5-methylisoxazole-4-propinoic acid receptor; Chronic renal failure; Hippocampus; Isoform of calcium/calmodulin-dependent protein kinase II; N-methyl-D-aspartate receptor