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Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics

S Akbarian, NJ Sucher, D Bradley, A Tafazzoli, D Trinh, WP Hetrick, SG Potkin, CA Sandman, WE Bunney Jr and EG Jones
Journal of Neuroscience 1 January 1996, 16 (1) 19-30; DOI: https://doi.org/10.1523/JNEUROSCI.16-01-00019.1996
S Akbarian
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
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NJ Sucher
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
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D Bradley
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
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A Tafazzoli
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
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D Trinh
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
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WP Hetrick
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
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SG Potkin
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
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CA Sandman
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
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WE Bunney Jr
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
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EG Jones
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
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Abstract

NMDA receptor antagonists can induce a schizophrenia-like psychosis, but the role of NMDA receptors in the pathophysiology of schizophrenia remains unclear. Expression patterns of mRNAs for five NMDA receptor subunits (NR1/NR2A-D) were determined by in situ hybridization in prefrontal, parieto-temporal, and cerebellar cortex of brains from schizophrenics and from neuroleptic-treated and nonmedicated controls. In the cerebral cortex of both schizophrenics and controls, mRNAs for NR1, NR2A, NR2B, and NR2D subunits were preferentially expressed in layers II/III, Va, and VIa, with much higher levels in the prefrontal than in the parieto-temporal cortex. Levels of mRNA for the NR2C subunit were very low overall. By contrast, the cerebellar cortex of both schizophrenics and controls contained very high levels of NR2C subunit mRNA, whereas levels for the other subunit mRNAs were very low, except NR1, for which levels were moderate. Significant alterations in the schizophrenic cohort were confined to the prefrontal cortex. Here there was a shift in the relative proportions of mRNAs for the NR2 subunit family, with a 53% relative increase in expression of the NR2D subunit mRNA. No comparable changes were found in neuroleptic-treated or untreated controls. These findings indicate regional heterogeneity of NMDA receptor subunit expression in human cerebral and cerebellar cortex. In schizophrenics, the alterations in expression of NR2 subunit mRNA in prefrontal cortex are potential indicators of deficits in NMDA receptor-mediated neurotransmission accompanying functional hypoactivity of the frontal lobes.

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The Journal of Neuroscience: 16 (1)
Journal of Neuroscience
Vol. 16, Issue 1
1 Jan 1996
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Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics
S Akbarian, NJ Sucher, D Bradley, A Tafazzoli, D Trinh, WP Hetrick, SG Potkin, CA Sandman, WE Bunney Jr, EG Jones
Journal of Neuroscience 1 January 1996, 16 (1) 19-30; DOI: 10.1523/JNEUROSCI.16-01-00019.1996

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Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics
S Akbarian, NJ Sucher, D Bradley, A Tafazzoli, D Trinh, WP Hetrick, SG Potkin, CA Sandman, WE Bunney Jr, EG Jones
Journal of Neuroscience 1 January 1996, 16 (1) 19-30; DOI: 10.1523/JNEUROSCI.16-01-00019.1996
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