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Lithium modulates tryptophan hydroxylase 2 gene expression and serotonin release in primary cultures of serotonergic raphe neurons.

Authors: Scheuch, K  Holtje, M  Budde, H  Lautenschlager, M  Heinz, A  Ahnert-Hilger, G  Priller, J 
Citation: Scheuch K, etal., Brain Res. 2010 Jan 11;1307:14-21. Epub 2009 Oct 17.
Pubmed: (View Article at PubMed) PMID:19840776
DOI: Full-text: DOI:10.1016/j.brainres.2009.10.027

Lithium salts are mood-stabilizing agents with acute antimanic properties and proven efficacy in the long-term prevention of manic and depressive episodes. Furthermore, lithium augmentation is a well-established strategy to treat depressed patients, which do not respond to antidepressants alone. There is evidence to suggest that these effects of lithium are due to a synergism with central serotonin (5-HT) neurotransmission. In this study, we investigated the effects of lithium chloride (LiCl, 1 mM) on 5-HT uptake and release in primary serotonergic neurons from rat raphe nuclei. Short-term (8 h) and long-term (14 days) treatment with LiCl resulted in a 20% and 23% increase in 5-HT release, but neither influenced 5-HT uptake across the plasma membrane nor vesicular 5-HT uptake. In lithium-treated raphe neurons, the inhibition of 5-HT uptake by fluoxetine was unchanged. Using real-time reverse transcriptase polymerase chain reaction and Western blotting, we examined the effect of lithium on tryptophan hydroxylase 2 (TPH2) expression, the rate-limiting enzyme in brain 5-HT biosynthesis. Short-term lithium treatment resulted in a 45% decrease in tph2 mRNA expression and a 31% reduction of TPH2 protein levels, which was completely compensated after long-term treatment. Our results suggest that lithium can modify tph2 gene expression and 5-HT release in raphe neurons, providing new insight into the serotonergic mechanisms of action of lithium.


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CRRD Object Information
CRRD ID: 2317083
Created: 2010-03-12
Species: All species
Last Modified: 2010-03-12
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.