Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia

H. M. Ibrahim, Jr Hogg A.J., D. J. Healy, V. Haroutunian, K. L. Davis, J. H. Meador-Woodruff

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Objective: Both thalamic and glutamatergic dysfunction have been implicated in the pathophysiology of schizophrenia. The authors examined ionotropic glutamate receptor expression in postmortem samples from patients with schizophrenia and comparison subjects, using the hypothesis that glutamate receptor expression differs in limbic nuclei of the thalamus in schizophrenia. Method: N-Methyl-D-aspartate (NMDA), AMPA, and kainate receptor expression was determined in six thalamic nuclei from 12 subjects with DSM-III-R diagnoses of schizophrenia and eight psychiatrically normal individuals. The authors used in situ hybridization to determine NMDAR1, NMDAR2A-NMDAR2D, gluR1-gluR7, KA1, and KA2 subunit mRNA levels and receptor autoradiography to determine binding to glutamate binding sites of the three receptor subtypes and to the glycine, polyamine, and ion channel binding sites of the NMDA receptor. Results: Glutamate receptor expression was lower at both transcriptional (NMDAR1, NMDAR2B, NMDAR2C, gluR1, gluR3, and KA2 subunit mRNAs) and posttranscriptional ([3H]ifenprodil and [3H]MDL105,519 binding to polyamine and glycine sites of the NMDA receptor) levels in the thalamus in patients with schizophrenia than in comparison subjects, but differences were most prominent in nuclei with reciprocal projections to limbic regions. Conclusions: Abnormalities in NMDA, AMPA, and kainate receptor expression in limbic thalamus are suggestive of the NMDA receptor hypoactivity hypothesis of schizophrenia and are consistent with diminished glutamatergic activity in the thalamus in schizophrenia. Alternatively, these results could suggest abnormal glutamatergic innervation in afferent and/or efferent regions, which are limbic structures that have been implicated in this illness. These results may provide a neurochemical anatomical substrate for antipsychotic therapies targeting ionotropic glutamate receptors.

Original languageEnglish (US)
Pages (from-to)1811-1823
Number of pages13
JournalAmerican Journal of Psychiatry
Volume157
Issue number11
DOIs
StatePublished - 2000

Fingerprint

Ionotropic Glutamate Receptors
Thalamic Nuclei
Schizophrenia
N-Methyl-D-Aspartate Receptors
Messenger RNA
Thalamus
Kainic Acid Receptors
AMPA Receptors
Glutamate Receptors
Polyamines
Glycine
Binding Sites
Autoradiography
Ion Channels
Diagnostic and Statistical Manual of Mental Disorders
Antipsychotic Agents
In Situ Hybridization
Glutamic Acid

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia. / Ibrahim, H. M.; Hogg A.J., Jr; Healy, D. J.; Haroutunian, V.; Davis, K. L.; Meador-Woodruff, J. H.

In: American Journal of Psychiatry, Vol. 157, No. 11, 2000, p. 1811-1823.

Research output: Contribution to journalArticle

Ibrahim, H. M. ; Hogg A.J., Jr ; Healy, D. J. ; Haroutunian, V. ; Davis, K. L. ; Meador-Woodruff, J. H. / Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia. In: American Journal of Psychiatry. 2000 ; Vol. 157, No. 11. pp. 1811-1823.
@article{5db79280aa04467389da7abfd7946713,
title = "Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia",
abstract = "Objective: Both thalamic and glutamatergic dysfunction have been implicated in the pathophysiology of schizophrenia. The authors examined ionotropic glutamate receptor expression in postmortem samples from patients with schizophrenia and comparison subjects, using the hypothesis that glutamate receptor expression differs in limbic nuclei of the thalamus in schizophrenia. Method: N-Methyl-D-aspartate (NMDA), AMPA, and kainate receptor expression was determined in six thalamic nuclei from 12 subjects with DSM-III-R diagnoses of schizophrenia and eight psychiatrically normal individuals. The authors used in situ hybridization to determine NMDAR1, NMDAR2A-NMDAR2D, gluR1-gluR7, KA1, and KA2 subunit mRNA levels and receptor autoradiography to determine binding to glutamate binding sites of the three receptor subtypes and to the glycine, polyamine, and ion channel binding sites of the NMDA receptor. Results: Glutamate receptor expression was lower at both transcriptional (NMDAR1, NMDAR2B, NMDAR2C, gluR1, gluR3, and KA2 subunit mRNAs) and posttranscriptional ([3H]ifenprodil and [3H]MDL105,519 binding to polyamine and glycine sites of the NMDA receptor) levels in the thalamus in patients with schizophrenia than in comparison subjects, but differences were most prominent in nuclei with reciprocal projections to limbic regions. Conclusions: Abnormalities in NMDA, AMPA, and kainate receptor expression in limbic thalamus are suggestive of the NMDA receptor hypoactivity hypothesis of schizophrenia and are consistent with diminished glutamatergic activity in the thalamus in schizophrenia. Alternatively, these results could suggest abnormal glutamatergic innervation in afferent and/or efferent regions, which are limbic structures that have been implicated in this illness. These results may provide a neurochemical anatomical substrate for antipsychotic therapies targeting ionotropic glutamate receptors.",
author = "Ibrahim, {H. M.} and {Hogg A.J.}, Jr and Healy, {D. J.} and V. Haroutunian and Davis, {K. L.} and Meador-Woodruff, {J. H.}",
year = "2000",
doi = "10.1176/appi.ajp.157.11.1811",
language = "English (US)",
volume = "157",
pages = "1811--1823",
journal = "American Journal of Psychiatry",
issn = "0002-953X",
publisher = "American Psychiatric Association",
number = "11",

}

TY - JOUR

T1 - Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia

AU - Ibrahim, H. M.

AU - Hogg A.J., Jr

AU - Healy, D. J.

AU - Haroutunian, V.

AU - Davis, K. L.

AU - Meador-Woodruff, J. H.

PY - 2000

Y1 - 2000

N2 - Objective: Both thalamic and glutamatergic dysfunction have been implicated in the pathophysiology of schizophrenia. The authors examined ionotropic glutamate receptor expression in postmortem samples from patients with schizophrenia and comparison subjects, using the hypothesis that glutamate receptor expression differs in limbic nuclei of the thalamus in schizophrenia. Method: N-Methyl-D-aspartate (NMDA), AMPA, and kainate receptor expression was determined in six thalamic nuclei from 12 subjects with DSM-III-R diagnoses of schizophrenia and eight psychiatrically normal individuals. The authors used in situ hybridization to determine NMDAR1, NMDAR2A-NMDAR2D, gluR1-gluR7, KA1, and KA2 subunit mRNA levels and receptor autoradiography to determine binding to glutamate binding sites of the three receptor subtypes and to the glycine, polyamine, and ion channel binding sites of the NMDA receptor. Results: Glutamate receptor expression was lower at both transcriptional (NMDAR1, NMDAR2B, NMDAR2C, gluR1, gluR3, and KA2 subunit mRNAs) and posttranscriptional ([3H]ifenprodil and [3H]MDL105,519 binding to polyamine and glycine sites of the NMDA receptor) levels in the thalamus in patients with schizophrenia than in comparison subjects, but differences were most prominent in nuclei with reciprocal projections to limbic regions. Conclusions: Abnormalities in NMDA, AMPA, and kainate receptor expression in limbic thalamus are suggestive of the NMDA receptor hypoactivity hypothesis of schizophrenia and are consistent with diminished glutamatergic activity in the thalamus in schizophrenia. Alternatively, these results could suggest abnormal glutamatergic innervation in afferent and/or efferent regions, which are limbic structures that have been implicated in this illness. These results may provide a neurochemical anatomical substrate for antipsychotic therapies targeting ionotropic glutamate receptors.

AB - Objective: Both thalamic and glutamatergic dysfunction have been implicated in the pathophysiology of schizophrenia. The authors examined ionotropic glutamate receptor expression in postmortem samples from patients with schizophrenia and comparison subjects, using the hypothesis that glutamate receptor expression differs in limbic nuclei of the thalamus in schizophrenia. Method: N-Methyl-D-aspartate (NMDA), AMPA, and kainate receptor expression was determined in six thalamic nuclei from 12 subjects with DSM-III-R diagnoses of schizophrenia and eight psychiatrically normal individuals. The authors used in situ hybridization to determine NMDAR1, NMDAR2A-NMDAR2D, gluR1-gluR7, KA1, and KA2 subunit mRNA levels and receptor autoradiography to determine binding to glutamate binding sites of the three receptor subtypes and to the glycine, polyamine, and ion channel binding sites of the NMDA receptor. Results: Glutamate receptor expression was lower at both transcriptional (NMDAR1, NMDAR2B, NMDAR2C, gluR1, gluR3, and KA2 subunit mRNAs) and posttranscriptional ([3H]ifenprodil and [3H]MDL105,519 binding to polyamine and glycine sites of the NMDA receptor) levels in the thalamus in patients with schizophrenia than in comparison subjects, but differences were most prominent in nuclei with reciprocal projections to limbic regions. Conclusions: Abnormalities in NMDA, AMPA, and kainate receptor expression in limbic thalamus are suggestive of the NMDA receptor hypoactivity hypothesis of schizophrenia and are consistent with diminished glutamatergic activity in the thalamus in schizophrenia. Alternatively, these results could suggest abnormal glutamatergic innervation in afferent and/or efferent regions, which are limbic structures that have been implicated in this illness. These results may provide a neurochemical anatomical substrate for antipsychotic therapies targeting ionotropic glutamate receptors.

UR - http://www.scopus.com/inward/record.url?scp=0033761169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033761169&partnerID=8YFLogxK

U2 - 10.1176/appi.ajp.157.11.1811

DO - 10.1176/appi.ajp.157.11.1811

M3 - Article

C2 - 11058479

AN - SCOPUS:0033761169

VL - 157

SP - 1811

EP - 1823

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

SN - 0002-953X

IS - 11

ER -