Cortical glutamatergic markers in schizophrenia.

Abstract

Post-mortem studies have yet to produce consistent findings on cortical glutamatergic markers in schizophrenia; therefore, it is not possible to fully understand the role of abnormal glutamatergic function in the pathology of the disorder. To better understand the changes in cortical glutamatergic markers in schizophrenia, we measured the binding of radioligands to the ionotropic glutamate receptors (N-methyl D-aspartate, [3H]CGP39653, [3H]MK-801), amino-3-hydroxy-5-methyl-4-isoxazole ([3H]AMPA), kainate ([3H]kainate), and the high-affinity glutamate uptake site ([3H]aspartate) using in situ radioligand binding with autoradiography and levels of mRNA for kainate receptors using in situ hybridization in the dorsolateral prefrontal cortex from 20 subjects with schizophrenia and 20 controls matched for age and sex. Levels of [3H]kainate binding were significantly decreased in cortical laminae I-II (p = 0.01), III-IV (p < 0.05), and V-VI (p < 0.01) from subjects with schizophrenia. By contrast, levels of [3H]MK-801, [3H]AMPA, [3H]aspartate, or [3H]CGP39653 binding did not differ between the diagnostic cohorts. Levels of mRNA for the GluR5 subunit were decreased overall (p < 0.05), with no changes in levels of mRNA for GluR6, GluR7, KA1, or KA2 in tissue from subjects with schizophrenia. These data indicate that the decreased number of kainate receptors in the dorsolateral prefrontal cortex in schizophrenia may result, in part, from reduced expression of the GluR5 receptor subunits.

• Authors: Elizabeth Scarr, Monica Beneyto, James H Meador-Woodruff, Brian Dean
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 30 Issue 8 Pg. 1521-31 (Aug 2005) ISSN: 0893-133X [Print] England
• PMID: 15886719 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Excitatory Amino Acid Agonists
• Excitatory Amino Acid Antagonists
• Receptors, Glutamate
• Tritium
• CGP 39653
• Glutamic Acid
• Dizocilpine Maleate
• 2-Amino-5-phosphonovalerate
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
• Kainic Acid

Topics

• 2-Amino-5-phosphonovalerate (analogs & derivatives, pharmacokinetics)
• Adult
• Aged
• Biomarkers (metabolism)
• Case-Control Studies
• Cerebral Cortex (drug effects, metabolism)
• Dizocilpine Maleate (pharmacokinetics)
• Excitatory Amino Acid Agonists (pharmacokinetics)
• Excitatory Amino Acid Antagonists (pharmacokinetics)
• Female
• Glutamic Acid (metabolism)
• Humans
• In Situ Hybridization (methods)
• Kainic Acid (pharmacokinetics)
• Male
• Middle Aged
• Postmortem Changes
• Radioligand Assay (methods)
• Receptors, Glutamate (genetics, metabolism)
• Schizophrenia (diagnosis, metabolism)
• Tritium (pharmacokinetics)
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (pharmacokinetics)