Document Detail


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:  2014-09-19    
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.
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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/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/MH/NIMH NIH HHS; P50 MH084053-03/MH/NIMH NIH HHS; P50 MH084053-04/MH/NIMH NIH HHS; R01 MH077159/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
Chemical
Reg. No./Substance:
0/Protein Precursors; 51110-01-1/Somatostatin
Comments/Corrections

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