Lithium ions enhance cysteine string protein gene expression in vivo and in vitro

Lithium is a well established pharmacotherapy for the treatment of recurrent manic-depressive illness. However, the mechanism by which lithium exerts its therapeutic action remains elusive. Here we report that lithium at 1 mM significantly increased the expression of cysteine string proteins (CSPs) in a pheochromocytoma cell line (PC12 cells) differentiated by nerve growth factor. These cells concomitantly exhibited increased expression of CSPs in their cell bodies and boutons. Enhanced CSP expression was also observed in the brain of rats fed a lithium-containing diet, which elevated serum lithium to a therapeutically relevant concentration of approximately 1.0 mM. However, both in vitro and in vivo, the expression of another synaptic vesicle protein, synaptophysin, and the t-SNARE, synaptosomal-associated protein of 25 kDa (SNAP-25), was not significantly altered by lithium. These observations indicate that lithium-induced changes of CSP gene expression may contribute to the therapeutic efficacy of this monovalent cation.