Cited by 422Treatment of Major DepressionNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression

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Feyissa, Anteneh M., Chandran, Agata, Stockmeier, Craig A., Karolewicz, Beata·2009·Progress in Neuro-Psychopharmacology and Biological Psychiatry

DOI 10.1016/j.pnpbp.2008.10.005PMC PMC2655629

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Abstract

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.

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Authors: Feyissa, A. M., Chandran, A., Stockmeier, C. A., & Karolewicz, B.
Affiliations: University of Mississippi Medical Center (US)
Corresponding author: Karolewicz, Beata
ORCID: Feyissa, Anteneh M.
Stockmeier, Craig A.
Karolewicz, Beata
Venue: Progress in Neuro-Psychopharmacology and Biological Psychiatry
Publisher: Elsevier BV
Published: 2009-02
Volume: 33
Issue: 1
Pages: 70-75
ISSN: 0278-5846 (ISSN-L)
DOI: 10.1016/j.pnpbp.2008.10.005
PMC: PMC2655629
OpenAlex: W2054535395
Cited by: 421
References: 46
Citations by year: 2026: 19 · 2025: 21 · 2024: 29 · 2023: 28 · 2022: 31 · 2021: 34 · 2020: 34 · 2019: 25 · 2018: 25 · 2017: 14 · 2016: 27 · 2015: 28 · 2014: 24 · 2013: 21 · 2012: 15
FWCI: 10.75
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (5p20rr017701-10)
National Institute of Mental Health (R01MH067996, MH67996)
National Center for Research Resources (P20-RR-017701, RR 17701)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: major depressive disorder, NMDA receptor, NR2A, NR2B, NR1 subunit, PSD-95, prefrontal cortex, glutamatergic neurotransmission, postmortem brain, antidepressant targets, glutamatergic dysfunction
MeSH terms: Disks Large Homolog 4 Protein, Adult, Carrier Proteins, Major Depressive Disorder, Female, Humans, Male, Membrane Proteins, Middle Aged, Nerve Tissue Proteins, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Prefrontal Cortex, Intracellular Signaling Peptides and Proteins

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Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression

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