Dietary lithium induces regional increases of mRNA encoding cysteine string protein in rat brain

Lithium salts are used to treat manic-depressive disorders; however, the mechanism by which lithium produces its therapeutic benefit remains obscure. The action of lithium may involve alterations of proteins important for regulating synaptic function. In this context, we observed recently that lithium at therapeutically relevant concentrations enhanced expression of cysteine string protein (csp) at the level of both mRNA and protein, in cell culture and in rat brain. Several lines of evidence have shown that csps are vital components of the regulated secretory pathway. We were interested whether lithium modulates expression of csp in specific brain regions. To study this issue, we analyzed the effects of chronic lithium administration (21 days) on csp mRNA levels in rat brain using in situ hybridization. Densitometric analysis revealed that lithium upregulated csp mRNA in several brain areas that are important for mood and behavior. This effect may be germane to understanding the beneficial action of lithium in mood disorders.