Lithium ions Up-regulate mRNAs encoding dense-core vesicle proteins in nerve growth factor-differentiated PC12 cells

We recently reported that lithium ions induced an up-regulation of cysteine string protein (CSP) gene expression in nerve growth factor (NGF)-differentiated PC12 cells but not in undifferentiated cells. Concomitantly, expression of two other proteins of regulated secretory pathways, synaptophysin (SY) and SNAP-25, was unaffected by lithium. To assess further the specificity of this effect of lithium, we used cDNA arrays. Our data indicate that lithium ions increase the level of mRNA for proteins such as secretogranin II and vesicular monoamine transporter 1 that are preferentially associated with large densecore secretory vesicles (LDCVs) without affecting mRNAs for proteins predominantly affiliated with small synaptic-like vesicles, including the vesicular acetylcholine transporter and SY. This action of lithium is detected in NGF-differentiated PC12 cells but not in undifferentiated cells. These observations suggest that lithium ions modulate the turnover of LDCVs, and this may play a role in mediating the therapeutic action of lithium in manic-depressive illness.