Document Detail

Lithium increases tyrosine hydroxylase levels both in vivo and in vitro.
MedLine Citation:
PMID:  9523597     Owner:  NLM     Status:  MEDLINE    
Lithium, a simple monovalent cation, is the mainstay in the treatment of manic-depressive illness, but despite extensive research, its mechanism of action remains to be elucidated. Because lithium requires chronic administration for therapeutic efficacy and because its beneficial effects last well beyond its discontinuation, it has been postulated that lithium may exert major effects at the genomic level. We have previously shown that lithium, at therapeutically relevant concentrations, increases gene expression through the activator protein-1 (AP-1) transcription factor pathway in vitro. In the present study, we have sought to determine if lithium also increases the expression of endogenous genes known to be regulated by AP-1 and have therefore investigated the effects of lithium on tyrosine hydroxylase (TH) levels. Male Wistar rats were treated with LiCl for 9 days (subacute) or 4 weeks (chronic), and TH levels were measured in frontal cortex, hippocampus, and striatum using immunoblotting. Chronic (but not subacute) lithium treatment resulted in significant increases in TH levels in rat frontal cortex, hippocampus, and striatum. Lithium (1 mM) also increased TH levels in human SH-SY5Y neuroblastoma cells in vitro, indicating that lithium increases TH levels in both rodent and human tissues, likely via a direct cellular effect. These effects are compatible with (but likely not exclusively due to) an effect on the DNA binding of the 12-O-tetradecanoylphorbol 13-acetate response element to the AP-1 family of transcription factors.
G Chen; P X Yuan; Y M Jiang; L D Huang; H K Manji
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  70     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1998 Apr 
Date Detail:
Created Date:  1998-04-23     Completed Date:  1998-04-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1768-71     Citation Subset:  IM    
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
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MeSH Terms
Corpus Striatum / drug effects,  enzymology
Frontal Lobe / drug effects,  enzymology
Hippocampus / drug effects,  enzymology
Lithium / pharmacology*
Rats, Wistar
Tumor Cells, Cultured
Tyrosine 3-Monooxygenase / metabolism*
Reg. No./Substance:
7439-93-2/Lithium; EC 3-Monooxygenase

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