Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks

被引:102
作者
Lenox, RH [1 ]
Wang, L [1 ]
机构
[1] Univ Penn, Sch Med, Dept Psychiat, Mol Neuropsychopharmacol Program, Philadelphia, PA 19104 USA
关键词
lithium; gene; protein kinase C (PKC); glycogen synthase-3 (GSK-3); myristoylated alanine-rich C-kinase sustrate (MARCKS);
D O I
10.1038/sj.mp.4001306
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The clinical efficacy of lithium in the prophylaxis of recurrent affective episodes in bipolar disorder is characterized by a lag in onset and remains for weeks to months after discontinuation. Thus, the long-term therapeutic effect of lithium likely requires reprogramming of gene expression. Protein kinase C and glycogen synthase kinase-3 signal transduction pathways are perturbed by chronic lithium at therapeutically relevant concentrations and have been implicated in modulating synaptic function in nerve terminals. These signaling pathways offer an opportunity to model critical signals for altering gene expression programs that underlie adaptive responses of neurons to long-term lithium exposure. While the precise physiological events critical for the clinical efficacy of lithium remain unknown, we propose that linking lithium-responsive genes as a regulatory network will provide a strategy to identify signature gene expression patterns that distinguish between therapeutic and nontherapeutic actions of lithium.
引用
收藏
页码:135 / 144
页数:10
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