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

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 recepto...

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Vydáno v:	Progress in neuro-psychopharmacology & biological psychiatry Ročník 33; číslo 1; s. 70 - 75
Hlavní autoři:	Feyissa, Anteneh M., Chandran, Agata, Stockmeier, Craig A., Karolewicz, Beata
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Amsterdam Elsevier Inc 01.02.2009 Elsevier
Témata:	Adult Adult and adolescent clinical studies Anterior prefrontal cortex Biological and medical sciences Carrier Proteins - metabolism Depression Depressive Disorder, Major - metabolism Depressive Disorder, Major - pathology Disks Large Homolog 4 Protein Female Glutamate receptors Humans Intracellular Signaling Peptides and Proteins - metabolism Major depressive disorder Male Medical sciences Membrane Proteins - metabolism Middle Aged Mood disorders Nerve Tissue Proteins - metabolism Neuropharmacology Pharmacology. Drug treatments Postmortem Postsynaptic density protein Prefrontal Cortex - metabolism Prefrontal Cortex - pathology Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Receptors, N-Methyl-D-Aspartate - metabolism Signal Transduction Glutamate receptors AMPA NR Anterior prefrontal cortex Postsynaptic density protein Postmortem NMDA MDD PFC PSD-95 Major depressive disorder Mood disorder Central nervous system Depression Glutamate receptor Prefrontal cortex Protein Encephalon Postsynaptic density NMDA receptor
ISSN:	0278-5846, 1878-4216
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0278-5846 1878-4216
DOI:	10.1016/j.pnpbp.2008.10.005