Document Detail


FLUOXETINE modifies the expression of serotonergic markers in a differentiation-dependent fashion in the mesencephalic neural cell line A1 mes c-myc.
MedLine Citation:
PMID:  17321503     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Serotonin (5-HT) is a neurotransmitter involved in a variety of CNS functions during development and in adulthood. 5-HT neurons are also involved in the pathogenesis of a number of psychiatric disorders. FLUOXETINE (FLX), a prototypic antidepressant, is a selective 5-HT uptake inhibitor (SSRI) with a demonstrated clinical efficacy in these disorders. SSRI, in a short-term period, binds 5-HT transporter (SERT) raising 5-HT levels at the synapse. Nevertheless, clinical improvement is observed only after 3-4 weeks of treatment. Recently, it has been shown that antidepressants, besides interfering with neurotransmission, can also display an effect on neural cells' proliferation and differentiation. Therefore it has been proposed that antidepressant may exert their clinical effects also acting on cellular functions other then neurotransmission. Here we show that a mesencephalic neural cell line, mes-c-myc A1 (A1) produces 5-HT and expresses SERT and both peripheral (TPH1) and CNS-specific (TPH2) form of tryptophan hydroxylase, the limiting enzyme in 5-HT biosynthesis. Cyclic AMP-dependent neuronal differentiation of A1 cells modulates the expression of TPHs. FLX, as well as citalopram (CIT), another SSRI inhibitor, modulates expression of serotonergic markers depending on the differentiation status of the cells. Interestingly, long-term but not short-term FLX treatment selectively modulates mRNA levels of TPH2, only in differentiated A1 cells. Finally, FLX and citalopram selectively decrease the proliferation rate of undifferentiated A1 cells, whereas have no effects on NIH-3T3 fibroblasts proliferation. In conclusion, neuronal differentiation of A1 cells not only modulates the expression of serotonergic markers, but appears to affect the response to FLX.
Authors:
Antonio Di Lieto; Damiana Leo; Floriana Volpicelli; Umberto di Porzio; Luca Colucci-D'Amato
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-28
Journal Detail:
Title:  Brain research     Volume:  1143     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-26     Completed Date:  2007-06-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1-10     Citation Subset:  IM    
Affiliation:
Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, Naples, Italy.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Cell Count
Cell Differentiation / drug effects*
Cell Line
Citalopram / pharmacology
Dose-Response Relationship, Drug
Embryo, Mammalian
Fluoxetine / pharmacology*
Gene Expression / drug effects
Mesencephalon / cytology*
Mice
Neurons / drug effects*
RNA, Messenger / biosynthesis
Reverse Transcriptase Polymerase Chain Reaction / methods
Serotonin / metabolism*
Serotonin Plasma Membrane Transport Proteins / genetics,  metabolism
Serotonin Uptake Inhibitors / pharmacology*
Time Factors
Tryptophan Hydroxylase / genetics,  metabolism
Vesicular Monoamine Transport Proteins / genetics,  metabolism
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Serotonin Plasma Membrane Transport Proteins; 0/Serotonin Uptake Inhibitors; 0/Slc18a2 protein, mouse; 0/Slc6a4 protein, mouse; 0/Vesicular Monoamine Transport Proteins; 50-67-9/Serotonin; 54910-89-3/Fluoxetine; 59729-33-8/Citalopram; EC 1.14.16.4/Tph1 protein, mouse; EC 1.14.16.4/Tph2 protein, mouse; EC 1.14.16.4/Tryptophan Hydroxylase

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