Document Detail

Repeated unpredictable stress and antidepressants differentially regulate expression of the bcl-2 family of apoptotic genes in rat cortical, hippocampal, and limbic brain structures.
MedLine Citation:
PMID:  17700647     Owner:  NLM     Status:  MEDLINE    
Apoptosis has been proposed as a contributing cellular mechanism to the structural alterations that have been observed in stress-related mood disorders. Antidepressants, on the other hand, are hypothesized to exert trophic and/or neuroprotective actions. The present study examined the regulation of the major antiapoptotic (Bcl-2, Bcl-xl) and proapoptotic (Bax) genes by repeated unpredictable stress (an animal model of depression) and antidepressant treatments (ADT). In adult rats, exposure to unpredictable stress reduced Bcl-2 mRNA levels in the central nucleus of the amygdala (CeA), cingulate (Cg), and frontal (Fr) cortices. Bcl-xl mRNA was significantly decreased in hippocampal subfields. In contrast, chronic administration of clinically effective antidepressants from four different classes, ie fluoxetine, reboxetine, tranylcypromine, and electroconvulsive seizures (ECS) upregulated Bcl-2 mRNA expression in the Cg, Fr, and CeA. Reboxetine, tranylcypromine, and ECS selectively increased Bcl-xl, but not Bcl-2 mRNA expression in the hippocampus. Chemical ADT but not ECS, robustly enhanced Bcl-2 expression in the medial amygdaloid nucleus and ventromedial hypothalamus. Fluoxetine did not influence Bcl-xl expression in the hippocampus, but it was the only ADT that decreased Bax expression in this region. In the CeA, again in direct contrast to the stress effects, exposure to all classes of ADTs significantly increased Bcl-2 mRNA. The selective regulation of Bcl-xl and Bax in hippocampal subfields and of Bcl-2 in the Cg cortex, amygdala, and hypothalamus suggests that these cellular adaptations contribute to the long-term neural plastic adaptations to stress and ADTs in cortical, hypothalamic, and limbic brain structures.
Therese A Kosten; Matthew P Galloway; Ronald S Duman; David S Russell; Carrol D'Sa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-08-15
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  33     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-14     Completed Date:  2008-09-24     Revised Date:  2011-05-18    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1545-58     Citation Subset:  IM    
Department of Psychiatry, Menninger Department of Psychiatry, Baylor College of Medicine and Michael E DeBakey Veterans Affairs, Houston, TX, USA.
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MeSH Terms
Antidepressive Agents / pharmacology,  therapeutic use*
Behavior, Animal
Brain* / drug effects,  metabolism,  pathology
Cerebral Cortex / drug effects,  metabolism
Disease Models, Animal
Gene Expression Regulation / drug effects*
Hippocampus / drug effects,  metabolism
Limbic System / drug effects,  metabolism
Proto-Oncogene Proteins c-bcl-2 / genetics,  metabolism*
Rats, Sprague-Dawley
Ribonucleases / pharmacology
Stress, Psychological* / drug therapy,  metabolism,  pathology
bcl-X Protein / genetics,  metabolism
Reg. No./Substance:
0/Antidepressive Agents; 0/Bcl2l1 protein, rat; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-X Protein; EC 3.1.-/Ribonucleases

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