Lithium and Signal Transduction
Numerous clinical studies have demonstrated that lithium is widely prescribed as a mood stabilizer in the treatment of bipolar mood disorder. An accumulation of evidences, resulted from the pharmacological studies of lithium, postulates several putative actions of this drug.10 These proposed actions include the inhibition of inositol monophosphatase, the modulation of GTP-binding proteins, and the inhibition of glycogen synthase kinase 3ß. These proposed actions are induced in response to an acute administration of lithium. However, since a long-term administration of lithium is required to obtain optimal therapeutic effects, changes in neuronal gene expression that are induced by an activation of transcription factors may be involved in the clinical efficacy of this drug. Numerous molecular pharmacological studies have demonstrated that several signal transduction pathways, such as the β-adrenoceptor-cAMP-protein kinase A or 5-HT2A-calcium (Ca2+)-Ca2+/calmodulin dependent protein kinase II, IV cascade regulate neuronal gene expression through the phosphorylation (activation) of a cAMP response element binding protein (CREB), a major transcription factor in the brain. In this context, the regulation of the expression and phosphorylation of CREB is thought to be an important molecular target of lithium action.
KeywordscAMP Response Element Binding BDNF mRNA cAMP Response Element Binding Protein PP2A Activity Major Transcription Factor
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- 6.T. Fukumoto, S. Morinobu, Y. Okamoto, A. Kagaya, and S. Yamawaki, Chronic lithium treatment increases the expression of brain-derived neurotrophic factor (BDNF) in the rat brain, Psychopharmacol. (in press).Google Scholar