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KMID : 0359920140330030132
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Korean Journal of Nephrology
2014 Volume.33 No. 3 p.132 ~ p.138
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Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of aCaMKII/NR2A synaptic complex and phosphorylated GluR1-containing AMPA receptor cascades
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Kim Jong-Wan
Ha Gyoung-Yim
Jung Yong-Wook
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Abstract
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Background: N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxazole-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. 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 aCaMKII were analyzed in the cornu ammonis (CA) 1 and CA3/dentate gyrus (DG) sub?elds 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 sub?eld, but not in the CA3/DG sub?elds. The CA1 sub?elds of CRF rats exhibited signi?cant decreases and increases, respectively, in the expressions of PSD-95/NR2B and aCaMKII/ NR2A synaptic complex. Moreover, increased phosphorylation of glutamate receptor type 1 (GluR1) AMPA receptor at ser831 was observed in the CA1 sub?eld after CRF.
Conclusion: 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 aCaMKII and subsequent activation of GluR1-containing AMPA receptors caused by the phosphorylation of GluR1 at ser831.
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KEYWORD
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Alpha-amino-3-hydroxy-5-methylisoxazole-4-propinoic acid receptor Chronic renal failure Hippocampus
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