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)-differen tiated PC12 cells but not in undifferentiated cells. Concomitantly, express ion of two other proteins of regulated secretory pathways, synaptophysin (S Y) and SNAP-25, was unaffected by lithium. To assess further the specificit y of this effect of lithium, we used cDNA arrays. Our data indicate that li thium ions increase the level of mRNA for proteins such as secretogranin II and vesicular monoamine transporter 1 that are preferentially associated w ith large dense-core secretory vesicles (LDCVs) without affecting mRNAs for proteins predominantly affiliated with small synaptic-like vesicles, inclu ding the vesicular acetylcholine transporter and SY. This action of lithium is detected in NGF-differentiated PC12 cells but not in undifferentiated c ells. These observations suggest that lithium ions modulate the turnover of LDCVs, and this may play a role in mediating the therapeutic action of lit hium in manic-depressive illness.