N-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophrenia.
OBJECTIVE
The N-methyl-D-aspartic acid (NMDA) class of glutamate receptors has received attention in the pathophysiology of schizophrenia because of the similarity between some schizophrenic symptoms and symptoms caused by NMDA antagonists. To determine if NMDA receptor abnormalities were present at the mRNA level, expression of NMDA receptor (NR) subunits NR(1), NR(2A), and NR(2B) was measured in specimens from the dorsolateral prefrontal cortex and the occipital cortex of elderly patients with schizophrenia and normal elderly subjects.


METHODS
Postmortem specimens from antemortem assessed and diagnosed elderly patients with schizophrenia (N=26) were compared with those from a neuropathologically and neuropsychiatrically normal elderly comparison group (N=13) and from patients with Alzheimer's disease (N=10). The mRNA expression of the NR(1), NR(2A), and NR(2B) subunits and of postsynaptic density 95 (PSD-95), a protein associated with postsynaptic NMDA receptors, was studied with quantitative real-time reverse transcriptase polymerase chain reaction.


RESULTS
Expression of NR(1) and NR(2A) but not NR(2B) subunits was higher in the dorsolateral prefrontal cortex and the occipital cortex of patients with schizophrenia than in the normal and Alzheimer's disease groups. In contrast, NR(1) expression was significantly lower in the Alzheimer's disease group. Occipital cortex expression of PSD-95 was higher in the schizophrenic subjects and correlated strongly with the expression of NR(2A) and NR(2B) in both cortical regions and with expression of NR(1) in the occipital cortex. These results were not influenced by neuroleptic exposure history, postmortem interval, or age of the subject.


CONCLUSIONS
NMDA receptor subunits are abnormally expressed in elderly patients with schizophrenia. The disproportionate expression of the NR(1) and NR(2A) subunits relative to NR(2B) expression may have implications for the pathophysiology of schizophrenia and the sensitivity of schizophrenic patients to glutamate and glutamatergic drugs.
Dracheva
S
S
Department of Psychiatry, Mount Sinai School of Medicine, Bronx Veterans Affairs Medical Center, NY 10468, USA.
Marras
S A
SA
Elhakem
S L
SL
Kramer
F R
FR
Davis
K L
KL
Haroutunian
V
V
D000199:Actins / Q000032:analysis / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D009778:Occipital Lobe / Q000737:chemistry / Q000378:metabolism; D017397:Prefrontal Cortex / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
D000199:Actins; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C501449:Dlg4 protein, rat; C409466:NR1 NMDA receptor; C033652:postsynaptic density proteins