RT Journal Article
SR Electronic
T1 Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 19
OP 30
DO 10.1523/JNEUROSCI.16-01-00019.1996
VO 16
IS 1
A1 S Akbarian
A1 NJ Sucher
A1 D Bradley
A1 A Tafazzoli
A1 D Trinh
A1 WP Hetrick
A1 SG Potkin
A1 CA Sandman
A1 WE Bunney, Jr
A1 EG Jones
YR 1996
UL http://www.jneurosci.org/content/16/1/19.abstract
AB 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.