Neuroprotective Effects of Lithium Relevant to Its Therapeutic Actions

Objective:Lithium has been used as a mood stabilizer for more than 50 years since its first use in the treatment of bipolar disorder. However, the mechanisms of its therapeutic actions remain unclear. Previous studies have shown neuroprotective and stress-attenuating effects of lithium which are thought to be related to its therapeutic actions. This article reviewed neuroprotective and stress-attenuating effects of lithium by searching data from previous studies. Methods:The literature on neuroprotective and stress-attenuating effects of lithium was searched using PubMed. Results:Lithium has the ability to protect neurons against a variety of insults. Lithium has been shown to prevent or attenuate the altered neural plasticity induced by stress at the molecular, structural, and behavioral levels, at least in animal studies. Neuroprotective effects of lithium have also been demonstrated in patients with bipolar disorder. The neuroprotective mechanisms of lithium include up-regulation of cytoprotective proteins, such as bcl-2, direct and indirect inhibition of glycogen synthase kinase 3-β, down-regulation of pro-apoptotic proteins, such as p38 and Bax, and activation of cAMP response element binding protein, with the resulting up-regulation of neurotrophic factors, such as brain-derived neurotrophic factor. Conclusion:These neuroprotective and stress-attenuating effects may contribute to the therapeutic actions of lithium.