TY - JOUR
T1 - Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression
AU - Feyissa, Anteneh M.
AU - Chandran, Agata
AU - Stockmeier, Craig A.
AU - Karolewicz, Beata
N1 - Funding Information:
The authors thank Drs. Grazyna Rajkowska, Dorota Maciag, and Jose-Javier Miguel-Hidalgo for assistance in anatomical positioning of measurements and tissue dissection. We thank Dr. John P. Kelly for editing the manuscript. We gratefully acknowledge the work of Drs. James C. Overholser, Herbert Y. Meltzer, Bryan L. Roth, George Jurjus, Ginny Dilley, Lisa Konick, Nicole Herbst and Lesa Dieter in the retrospective psychiatric diagnoses. The excellent assistance of the Cuyahoga County Coroner's Office, Cleveland, OH is greatly appreciated. This publication was supported by RR17701; American Foundation for Suicide Prevention (Young Investigator Award to BK); NARSAD (Young Investigator Award to BK), and MH67996.
PY - 2009/2/1
Y1 - 2009/2/1
N2 - Recent neuroimaging and postmortem studies have demonstrated abnormalities in glutamatergic transmission in major depression. Glutamate NMDA (N-methyl-d-aspartate) receptors are one of the major mediators of excitatory neurotransmission in the central nervous system. At synaptic sites, NMDA receptors are linked with postsynaptic density protein-95 (PSD-95) that plays a key role in mediating trafficking, clustering, and downstream signaling events, following receptor activation. In this study, we examined the expression of NMDA receptor subunits NR1, NR2A, and NR2B as well as PSD-95 in the anterior prefrontal cortex (PFC) using Western blot method. Cortical samples were obtained from age, gender and postmortem interval matched depressed and psychiatrically healthy controls. The results revealed that there was a reduced expression of the NMDA receptor subunits NR2A (- 54%) and NR2B (- 48%), and PSD-95 protein level (- 40%) in the PFC of depressed subjects relative to controls, with no change in the NR1 subunit. The alterations in NMDA receptor subunits, especially the NR2A and NR2B, as well as PSD-95 suggest an abnormality in the NMDA receptor signaling in the PFC in major depression. Our findings in conjunction with recent clinical, cellular, and neuroimaging studies further implicate the involvement of glutamate neurotransmission in the pathophysiology of depression. This study provides additional evidence that NMDA receptor complex is a target for discovery of novel antidepressants.
AB - Recent neuroimaging and postmortem studies have demonstrated abnormalities in glutamatergic transmission in major depression. Glutamate NMDA (N-methyl-d-aspartate) receptors are one of the major mediators of excitatory neurotransmission in the central nervous system. At synaptic sites, NMDA receptors are linked with postsynaptic density protein-95 (PSD-95) that plays a key role in mediating trafficking, clustering, and downstream signaling events, following receptor activation. In this study, we examined the expression of NMDA receptor subunits NR1, NR2A, and NR2B as well as PSD-95 in the anterior prefrontal cortex (PFC) using Western blot method. Cortical samples were obtained from age, gender and postmortem interval matched depressed and psychiatrically healthy controls. The results revealed that there was a reduced expression of the NMDA receptor subunits NR2A (- 54%) and NR2B (- 48%), and PSD-95 protein level (- 40%) in the PFC of depressed subjects relative to controls, with no change in the NR1 subunit. The alterations in NMDA receptor subunits, especially the NR2A and NR2B, as well as PSD-95 suggest an abnormality in the NMDA receptor signaling in the PFC in major depression. Our findings in conjunction with recent clinical, cellular, and neuroimaging studies further implicate the involvement of glutamate neurotransmission in the pathophysiology of depression. This study provides additional evidence that NMDA receptor complex is a target for discovery of novel antidepressants.
KW - Anterior prefrontal cortex
KW - Glutamate receptors
KW - Major depressive disorder
KW - Postmortem
KW - Postsynaptic density protein
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U2 - 10.1016/j.pnpbp.2008.10.005
DO - 10.1016/j.pnpbp.2008.10.005
M3 - Article
C2 - 18992785
AN - SCOPUS:58149357209
VL - 33
SP - 70
EP - 75
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
SN - 0278-5846
IS - 1
ER -