LITHIUM ATTENUATES NERVE GROWTH FACTOR-INDUCED ACTIVATION OF AP-1 DNA-BINDING ACTIVITY IN PC12 CELLS

This investigation tested if lithium, the primary therapeutic agent fo r bipolar mood disorder, modulated activation of the AP-1 transcriptio n factor in PC12 cells treated with nerve growth factor (NGF), which i nduces robust responses in these cells. NGF induced large, time-depend ent increases in AP-2 DNA binding activity. Pretreatment with 5 mmol/L lithium for 24 h reduced AP-1 induction by NGF by 42%; shorter treatm ents and lower concentrations of lithium had smaller inhibitory effect s on AP-1. This effect of lithium tons not limited to AP-1, as if also inhibited NGF-induced cyclic AMP responsive element (CRE) DNA binding activity. In contrast, activation of AP-1 and CRE by forskolin was un affected by lithium. AP-1 constituent proteins were differentially sus ceptible to lithium, as cJun was reduced by 55%, cFos was unaffected b y lithium, and an intermediate effect was observed with Jun B, These r esults reveal that lithium modulates the activation of transcription f actors in a neuronal cell model, indicating that selective regulation of gene expression may contribute to the long term in vivo effect of l ithium. (C) 1997 American College of Neuropsychopharmacology.