Document Detail

Progesterone pretreatment enhances serotonin-stimulated BDNF gene expression in rat c6 glioma cells through production of 5alpha-reduced neurosteroids.
MedLine Citation:
PMID:  18219447     Owner:  NLM     Status:  MEDLINE    
Tricyclic antidepressants and selective serotonin reuptake inhibitors are considered in theory to induce the outflow of neurotransmitters, norepinephrine, and serotonin from the synapses as a consequence of inhibiting their reuptake into the nerve terminals, resulting in the stimulation of glial cells surrounding the synapses in the brain. Then, we have investigated the direct actions of neurotransmitters on glial cell metabolism and function using rat C6 glioma cells as an in vitro model system and suggested that these neurotransmitters induce their differentiation probably through the production of 5alpha-reduced neurosteroids. On the other hand, the stimulation of the glioma cells with serotonin has been reported to enhance brain-derived neurotrophic factor (BDNF) gene expression, which may be closely related to the beneficial effects of antidepressant drugs. In the present study, to evaluate BDNF expression in differentiated glial cells, the glioma cells were pretreated with progesterone, and the effect of serotonin on BDNF messenger RNA levels in these cells was examined. Progesterone pretreatment enhanced the stimulatory action of serotonin on BDNF gene expression, and the enhancement of serotonin action observed in the cells pretreated with progesterone was almost completely abolished by finasteride, an inhibitor of the enzyme involved in the production of 5alpha-reduced neurosteroids. These findings propose the possibility that neurosteroid-mediated glial cell differentiation may result in the enhancement of serotonin-stimulated BDNF gene expression, which is considered to contribute to the survival, regeneration, and plasticity of neuronal cells in the brain, and hence, leading to the improvement of mood disorders and other symptoms in depressive patients.
Kyoji Morita; Song Her
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-01-25
Journal Detail:
Title:  Journal of molecular neuroscience : MN     Volume:  34     ISSN:  0895-8696     ISO Abbreviation:  J. Mol. Neurosci.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-28     Completed Date:  2008-06-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9002991     Medline TA:  J Mol Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  193-200     Citation Subset:  IM    
Department of Pharmacology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
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MeSH Terms
Antidepressive Agents, Tricyclic / pharmacology
Brain / drug effects*,  metabolism
Brain-Derived Neurotrophic Factor / genetics*
Cell Differentiation / drug effects,  genetics
Cell Line, Tumor
Drug Synergism
Enzyme Inhibitors / pharmacology
Finasteride / pharmacology
Gene Expression Regulation / drug effects*,  genetics
Neuroglia / drug effects*,  metabolism
Neuronal Plasticity / drug effects,  genetics
Presynaptic Terminals / drug effects,  metabolism
Progesterone / pharmacology*
RNA, Messenger / drug effects,  metabolism
Serotonin / pharmacology*
Serotonin Uptake Inhibitors / pharmacology
Testosterone 5-alpha-Reductase / drug effects,  metabolism
Up-Regulation / drug effects,  genetics
Reg. No./Substance:
0/Antidepressive Agents, Tricyclic; 0/Brain-Derived Neurotrophic Factor; 0/Enzyme Inhibitors; 0/RNA, Messenger; 0/Serotonin Uptake Inhibitors; 50-67-9/Serotonin; 57-83-0/Progesterone; 98319-26-7/Finasteride; EC 5-alpha-Reductase

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

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