Altered distribution of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4) and the N-methyl-D-aspartate receptor subunit NMDAR1 in the hippocampus of patients with temporal lobe epilepsy

Ingmar Blümcke, Heinz Beck, Björn Scheffler, Patrick R. Hof, John Morrison, Helmut K. Wolf, Johannes Schramm, Christian E. Elger, Otmar D. Wiestler

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

In patients with therapy-refractory temporal lobe epilepsy (TLE), alterations of glutamate receptors have been proposed as a mechanism for enhanced excitability. Using commercially available monoclonal antibodies specific for the N-methyl-D-aspartate (NMDA) receptor subunit NMDAR1 and for the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4), we have examined the distribution of these polypeptides in human hippocampal tissue that was surgically removed from patients with intractable TLE. Surgical specimens were classified according to the presence of Ammon's horn sclerosis (AHS) or a focal lesion in the temporal lobe. Cell counts and a densitometric analysis of the immunoreactivity patterns were carried out for all hippocampal subfields. NMDAR1 and GluR2(4) levels were markedly reduced in patients with AHS, primarily in those subfields with substantial neuronal cell loss (in particular CA1, CA4 and CA3), compared to those seen in patients with focal lesions and in control specimens obtained at autopsy. In contrast, the molecular layer of the dentate gyrus (DG-ML) showed significantly higher levels of GluR2(4) immunoreactivity in AHS compared to control tissue, while NMDAR1 showed no significant up-regulation in this sublayer. When the receptor staining intensity was normalized for alterations in neuronal density, no significant alterations could be detected except for an increase in GluR2(4) in the DG-ML of patients with AHS. These changes may reflect synaptic reorganization observed in the DG-ML of specimens from patients with chronic intractable TLE.

Original languageEnglish (US)
Pages (from-to)576-587
Number of pages12
JournalActa Neuropathologica
Volume92
Issue number6
DOIs
StatePublished - Dec 1 1996
Externally publishedYes

Fingerprint

Isoxazoles
Temporal Lobe Epilepsy
Propionates
N-Methyl-D-Aspartate Receptors
Hippocampus
Sclerosis
Dentate Gyrus
Glutamate Receptors
Temporal Lobe
AMPA 2 glutamate receptor ionotropic
NMDA receptor A1
Autopsy
Up-Regulation
Cell Count
Monoclonal Antibodies
Staining and Labeling
Peptides

Keywords

  • Ammon's horn sclerosis
  • Excitatory amino acids
  • Quantitative image analysis
  • Therapy-refractory epilepsy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Altered distribution of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4) and the N-methyl-D-aspartate receptor subunit NMDAR1 in the hippocampus of patients with temporal lobe epilepsy. / Blümcke, Ingmar; Beck, Heinz; Scheffler, Björn; Hof, Patrick R.; Morrison, John; Wolf, Helmut K.; Schramm, Johannes; Elger, Christian E.; Wiestler, Otmar D.

In: Acta Neuropathologica, Vol. 92, No. 6, 01.12.1996, p. 576-587.

Research output: Contribution to journalArticle

Blümcke, Ingmar ; Beck, Heinz ; Scheffler, Björn ; Hof, Patrick R. ; Morrison, John ; Wolf, Helmut K. ; Schramm, Johannes ; Elger, Christian E. ; Wiestler, Otmar D. / Altered distribution of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4) and the N-methyl-D-aspartate receptor subunit NMDAR1 in the hippocampus of patients with temporal lobe epilepsy. In: Acta Neuropathologica. 1996 ; Vol. 92, No. 6. pp. 576-587.
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abstract = "In patients with therapy-refractory temporal lobe epilepsy (TLE), alterations of glutamate receptors have been proposed as a mechanism for enhanced excitability. Using commercially available monoclonal antibodies specific for the N-methyl-D-aspartate (NMDA) receptor subunit NMDAR1 and for the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4), we have examined the distribution of these polypeptides in human hippocampal tissue that was surgically removed from patients with intractable TLE. Surgical specimens were classified according to the presence of Ammon's horn sclerosis (AHS) or a focal lesion in the temporal lobe. Cell counts and a densitometric analysis of the immunoreactivity patterns were carried out for all hippocampal subfields. NMDAR1 and GluR2(4) levels were markedly reduced in patients with AHS, primarily in those subfields with substantial neuronal cell loss (in particular CA1, CA4 and CA3), compared to those seen in patients with focal lesions and in control specimens obtained at autopsy. In contrast, the molecular layer of the dentate gyrus (DG-ML) showed significantly higher levels of GluR2(4) immunoreactivity in AHS compared to control tissue, while NMDAR1 showed no significant up-regulation in this sublayer. When the receptor staining intensity was normalized for alterations in neuronal density, no significant alterations could be detected except for an increase in GluR2(4) in the DG-ML of patients with AHS. These changes may reflect synaptic reorganization observed in the DG-ML of specimens from patients with chronic intractable TLE.",
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AU - Blümcke, Ingmar

AU - Beck, Heinz

AU - Scheffler, Björn

AU - Hof, Patrick R.

AU - Morrison, John

AU - Wolf, Helmut K.

AU - Schramm, Johannes

AU - Elger, Christian E.

AU - Wiestler, Otmar D.

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