Document Detail


Neuronal tryptophan hydroxylase mRNA expression in the human dorsal and median raphe nuclei: major depression and suicide.
MedLine Citation:
PMID:  16192985     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Major depressive disorder (MDD) and suicide are associated with deficient serotonergic neurotransmission. Tryptophan hydroxylase (TPH) is the rate-limiting biosynthetic enzyme for serotonin. Previously, we reported elevated levels of TPH protein in the dorsal raphe nucleus (DRN) of depressed suicides and now examine expression of neuronal TPH2 mRNA in a cohort of matched controls and depressed suicides (n = 11 pairs). DRN TPH2 mRNA was measured by densitometric analysis of autoradiograms from in situ hybridization histochemistry experiments. TPH2 mRNA is confirmed as the raphe-specific isoform of TPH in human brain, and is expressed in neurons throughout the anteroposterior extent of the DRN and median raphe nucleus (MRN). TPH2 mRNA expression correlates with TPH protein distribution in the DRN, and has a negative correlation with age. In drug-free suicides, TPH2 expression is 33% higher in the DRN and 17% higher in the MRN as compared to matched nonpsychiatric controls. Higher levels of TPH2 mRNA were found throughout the entire extent of the rostrocaudal axis of the DRN, and were not specific to any single subnucleus. Higher TPH2 mRNA expression may explain more TPH protein observed in depressed suicides and reflect a homeostatic response to deficient brain serotonergic transmission.
Authors:
Helene Bach-Mizrachi; Mark D Underwood; Suham A Kassir; Mihran J Bakalian; Etienne Sibille; Hadassah Tamir; J John Mann; Victoria Arango
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  31     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-17     Completed Date:  2006-05-25     Revised Date:  2013-09-23    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  814-24     Citation Subset:  IM    
Affiliation:
Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Age Factors
Aged
Aged, 80 and over
Analysis of Variance
Autoradiography / methods
Depressive Disorder, Major / genetics,  metabolism*
Female
Gene Expression / physiology*
Humans
In Situ Hybridization / methods
Male
Middle Aged
RNA, Messenger / metabolism
Raphe Nuclei / metabolism*
Suicide*
Tryptophan Hydroxylase / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
MH40210/MH/NIMH NIH HHS; MH62185/MH/NIMH NIH HHS; MH64168/MH/NIMH NIH HHS; T32 MH015144/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; EC 1.14.16.4/TPH2 protein, human; EC 1.14.16.4/Tryptophan Hydroxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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