| Reduced somatostatin in subgenual anterior cingulate cortex in major depression. | |
| | |
MedLine Citation:
|
PMID: 21232602 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Converging evidence suggests a central role for dysfunction of the subgenual anterior cingulate cortex (sgACC) in the pathophysiology of major depressive disorder (MDD). Underlying mechanisms may include altered GABAergic function. Expression of somatostatin (SST), an inhibitory neuropeptide localized to a subset of GABA neurons, has been shown to be lower in the dorsolateral prefrontal cortex of male MDD subjects. Here, to investigate whether alterations in SST may contribute to sgACC dysfunction in MDD, and whether the alterations display sex-specificity, we measured sgACC SST at the mRNA and precursor peptide levels in a large cohort of subjects with MDD. SST mRNA levels were analyzed by quantitative PCR (qPCR) in the postmortem sgACC from male (n=26) and female (n=25) subjects with MDD and sex-matched subjects with no psychiatric diagnosis (n=51). Prepro-SST protein levels were assessed in a subset of subjects (n=42 pairs) by semi-quantitative Western blot. The mRNA expression of SST was significantly reduced by 38% in female subjects and by 27% in male subjects with MDD. The characteristic age-related decline in SST expression was observed in control (Pearson R=-0.357, p=0.005) but not MDD (R=-0.104, p=0.234) subjects, as low expression was detected across ages in MDD subjects. Protein expression was similarly reduced by 19% in both MDD groups, and findings were more robust in female (p=0.0056) than in males (p=0.0373) compared to respective controls. In conclusion, low SST represents a robust pathological finding in MDD. Specifically, alterations in SST signaling and/or SST-bearing GABA neurons may represent a critical pathophysiological entity that contributes to sgACC dysfunction and that matches to the high female vulnerability to develop MDD. |
| | |
Authors:
|
Adam Tripp; Rama S Kota; David A Lewis; Etienne Sibille |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-01-11 |
Journal Detail:
|
Title: Neurobiology of disease Volume: 42 ISSN: 1095-953X ISO Abbreviation: Neurobiol. Dis. Publication Date: 2011 Apr |
Date Detail:
|
Created Date: 2011-02-14 Completed Date: 2011-12-23 Revised Date: 2012-11-21 |
Medline Journal Info:
|
Nlm Unique ID: 9500169 Medline TA: Neurobiol Dis Country: United States |
Other Details:
|
Languages: eng Pagination: 116-24 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Psychiatry, University of Pittsburgh, PA 15312, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adolescent Adult Aged Cohort Studies Depressive Disorder, Major / metabolism*, physiopathology Down-Regulation* Female Gyrus Cinguli / metabolism*, pathology, physiopathology Humans Male Middle Aged Neural Pathways / metabolism, physiology, physiopathology Protein Precursors / antagonists & inhibitors, biosynthesis, physiology Somatostatin / antagonists & inhibitors*, biosynthesis, physiology Young Adult |
| Grant Support | |
ID/Acronym/Agency:
|
K02 MH084060/MH/NIMH NIH HHS; K02 MH084060-03/MH/NIMH NIH HHS; K02 MH084060-04/MH/NIMH NIH HHS; MH077159/MH/NIMH NIH HHS; MH084053/MH/NIMH NIH HHS; MH084060/MH/NIMH NIH HHS; MH45156/MH/NIMH NIH HHS; P50 MH045156-10/MH/NIMH NIH HHS; P50 MH045156-11/MH/NIMH NIH HHS; P50 MH045156-12/MH/NIMH NIH HHS; P50 MH084053-03/MH/NIMH NIH HHS; P50 MH084053-04/MH/NIMH NIH HHS; R01 MH077159-01A1/MH/NIMH NIH HHS; R01 MH077159-02/MH/NIMH NIH HHS; R01 MH077159-03/MH/NIMH NIH HHS; R01 MH077159-04/MH/NIMH NIH HHS; R01 MH077159-06/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Protein Precursors; 51110-01-1/Somatostatin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A prolonged pharmacological blockade of type-5 metabotropic glutamate receptors protects cultured sp...
Next Document: Assays for studying nucleated aggregation of polyglutamine proteins.