Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of αCaMKII/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 α isoform of calcium/calmodulin-dependent protein kinase II (αCaMKII) is fundamentally involved in the regulation of working memory. The...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
The Korean Society of Nephrology
2014-09-01
|
Series: | Kidney Research and Clinical Practice |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211913214000837 |
id |
doaj-4b1d086741614094898f4fa79adcb88f |
---|---|
record_format |
Article |
spelling |
doaj-4b1d086741614094898f4fa79adcb88f2020-11-25T01:54:24ZengThe Korean Society of NephrologyKidney Research and Clinical Practice2211-91322014-09-0133313213810.1016/j.krcp.2014.07.003Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of αCaMKII/NR2A synaptic complex and phosphorylated GluR1-containing AMPA receptor cascadesJong Wan Kim0Gyoung Yim Ha1Yong Wook Jung2Section of Neuroscience Research, Medical Institute of Dongguk University, Gyeongju, KoreaDepartment of Laboratory Medicine, College of Medicine, Dongguk University, Gyeongju, KoreaSection of Neuroscience Research, Medical Institute of Dongguk University, Gyeongju, KoreaBackground: 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. 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 αCaMKII and subsequent activation of GluR1-containing AMPA receptors caused by the phosphorylation of GluR1 at ser831.http://www.sciencedirect.com/science/article/pii/S2211913214000837Alpha-amino-3-hydroxy-5-methylisoxazole-4-propinoic acid receptorChronic renal failureHippocampusIsoform of calcium/calmodulin-dependent protein kinase IIN-methyl-D-aspartate receptor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jong Wan Kim Gyoung Yim Ha Yong Wook Jung |
spellingShingle |
Jong Wan Kim Gyoung Yim Ha Yong Wook Jung Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of αCaMKII/NR2A synaptic complex and phosphorylated GluR1-containing AMPA receptor cascades Kidney Research and Clinical Practice 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 |
author_facet |
Jong Wan Kim Gyoung Yim Ha Yong Wook Jung |
author_sort |
Jong Wan Kim |
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 |
title_short |
Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of αCaMKII/NR2A synaptic complex and phosphorylated GluR1-containing AMPA receptor cascades |
title_full |
Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of αCaMKII/NR2A synaptic complex and phosphorylated GluR1-containing AMPA receptor cascades |
title_fullStr |
Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of αCaMKII/NR2A synaptic complex and phosphorylated GluR1-containing AMPA receptor cascades |
title_full_unstemmed |
Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of αCaMKII/NR2A synaptic complex and phosphorylated GluR1-containing AMPA receptor cascades |
title_sort |
chronic renal failure induces cell death in rat hippocampal ca1 via upregulation of αcamkii/nr2a synaptic complex and phosphorylated glur1-containing ampa receptor cascades |
publisher |
The Korean Society of Nephrology |
series |
Kidney Research and Clinical Practice |
issn |
2211-9132 |
publishDate |
2014-09-01 |
description |
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.
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 αCaMKII and subsequent activation of GluR1-containing AMPA receptors caused by the phosphorylation of GluR1 at ser831. |
topic |
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 |
url |
http://www.sciencedirect.com/science/article/pii/S2211913214000837 |
work_keys_str_mv |
AT jongwankim chronicrenalfailureinducescelldeathinrathippocampalca1viaupregulationofacamkiinr2asynapticcomplexandphosphorylatedglur1containingampareceptorcascades AT gyoungyimha chronicrenalfailureinducescelldeathinrathippocampalca1viaupregulationofacamkiinr2asynapticcomplexandphosphorylatedglur1containingampareceptorcascades AT yongwookjung chronicrenalfailureinducescelldeathinrathippocampalca1viaupregulationofacamkiinr2asynapticcomplexandphosphorylatedglur1containingampareceptorcascades |
_version_ |
1724987721599942656 |