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Author Notes:

Corresponding author. Medical Center Boulevard, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States. Tel.: +1 336 716 8620; fax: +1 336 716 8501. shemby@wfubmc.edu

Dr. Hemby conceptualized the scientific question, provided the scientific infrastructure for the study, worked in conjunction with Dr. O’Connor in the design of the study, data analysis and writing of the manuscript.

Dr. O’Connor worked in conjunction with Dr. Hemby in the design of the study, data analysis and writing of the manuscript. Dr. O’Connor conducted the sample preparation and qPCR analysis.

The authors acknowledge and appreciate the technical assistance of Brian Horman in the preparation of the photomicrographs.

Postmortem brain tissue was donated by the Stanley Medical Research Institute’s Neuropathology Consortium.

We are indebted to the altruism and support of the individuals and families for the donation of tissue for research.

Dr. Hemby has served as a consultant for Ortho-McNeil Janssen Scientific Affairs, Johnson and Johnson Pharmaceuticals and Amgen, Inc. None of these consultancies have influence this research.

Dr. O’Connor does not have conflicts of interest.

Subjects:

Research Funding:

The research was funded in part by grants from the NIHMH074313 (SEH) and the Stanley Medical Research Institute (SEH).

Keywords:

  • AMPA
  • NMDA
  • Pyramidal cell
  • Schizophrenia
  • Dorsolateral prefrontal cortex
  • Laser capture microdissection
  • Quantitative PCR

Elevated GRIA1 mRNA expression in Layer II/III and V pyramidal cells of the DLPFC in schizophrenia

Tools:

Journal Title:

Schizophrenia Research

Volume:

Volume 97, Number 1-3

Publisher:

, Pages 277-288

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The functional integrity of the dorsolateral prefrontal cortex (DLPFC) is altered in schizophrenia leading to profound deficits in working memory and cognition. Growing evidence indicates that dysregulation of glutamate signaling may be a significant contributor to the pathophysiology mediating these effects; however, the contribution of NMDA and AMPA receptors in the mediation of this deficit remains unclear. The equivocality of data regarding ionotropic glutamate receptor alterations of subunit expression in the DLPFC of schizophrenics is likely reflective of subtle alterations in the cellular and molecular composition of specific neuronal populations within the region. Given previous evidence of Layer II/III and V pyramidal cell alterations in schizophrenia and the significant influence of subunit composition on NMDA and AMPA receptor function, laser capture microdissection combined with quantitative PCR was used to examine the expression of AMPA (GRIA1-4) and NMDA (GRIN1, 2A and 2B) subunit mRNA levels in Layer II/III and Layer V pyramidal cells in the DLPFC. Comparisons were made between individuals diagnosed with schizophrenia, bipolar disorder, major depressive disorder and controls (n=15/group). All subunits were expressed at detectable levels in both cell populations for all diseases as well as for the control group. Interestingly, GRIA1 mRNA was significantly increased in both cell types in the schizophrenia group compare to controls, while similar trends were observed in major depressive disorder (Layers II/III and V) and bipolar disorder (Layer V). These data suggest that increased GRIA1 subunit expression may contribute to schizophrenia pathology.

Copyright information:

© 2007 Published by Elsevier B.V.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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