Kidney Res Clin Pract.  2014 Sep;33(3):132-138. 10.1016/j.krcp.2014.07.003.

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

• Kim JW
• Ha GY
• Jung YW

• KMID: 2028687
• DOI: http://doi.org/10.1016/j.krcp.2014.07.003

Abstract

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 alpha isoform of calcium/calmodulin-dependent protein kinase II (alphaCaMKII) 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 alphaCaMKII 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 alphaCaMKII/NR2A synaptic complex. Moreover, increased phosphorylation of glutamate receptor type 1 (GluR1) AMPA receptor at ser831 was observed in the CA1 subfield 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 alphaCaMKII and subsequent activation of GluR1-containing AMPA receptors caused by the phosphorylation of GluR1 at ser831.

Keyword

Alpha-amino-3-hydroxy-5-methylisoxazole-4-propinoic acid receptor; Chronic renalfailure; Hippocampus; Isoform ofcalcium/calmodulin-dependent proteinkinaseII; N-methyl-D-aspartatereceptor

MeSH Terms

Animals
Cell Death*
Hippocampus
Immunoblotting
Immunoprecipitation
Kidney Failure, Chronic*
Memory
Memory, Short-Term
N-Methylaspartate
Neurons
Phosphorylation
Protein Kinases
Rats*
Receptors, AMPA*
Receptors, Glutamate
Receptors, N-Methyl-D-Aspartate
Up-Regulation*
Uremia
N-Methylaspartate
Protein Kinases
Receptors, AMPA
Receptors, Glutamate
Receptors, N-Methyl-D-Aspartate