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

Kathrin Scheuch, Markus Höltje, Holger Budde, Marion Lautenschlager, Andreas Heinz, Gudrun Ahnert-Hilger, Josef Priller

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalBrain Research
Volume1307
DOIs
StatePublished - 11 Jan 2010
Externally publishedYes

Keywords

  • Cell culture
  • Lithium
  • Serotonergic raphe neurons
  • Serotonin release
  • Serotonin uptake
  • Tryptophan hydroxylase 2

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