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Molecular mechanisms of the effect of the mood stabilizer lithium
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Lithium salts are used to treat bipolar disorder, but§ the mechanisms accounting for the clinical efficacy are not§ completely understood. Chronic treatment with lithium is§ required to establish mood stabilization, suggesting the§ involvement of processes of neural plasticity. CREB (cAMP§ response element binding protein) is a transcription factor§ known to mediate neuronal adaptation. Recently, the§ CREB-coactivator TORC (transducer of regulated CREB) has been§ identified as a novel target of lithium. In the present§ study, several different methods were used to examine the§ molecular mechanism by which lithium stimulates cAMP-induced§ CRE/CREB-mediated gene transcription through TORC. The§ acquired data support the notion that lithium directly§ facilitates the interaction between CREB and TORC, thereby§ enhancing CREB-directed transcription. Thus the study§ suggests a novel mechanism of lithium action that may§ contribute to the therapeutic effect of lithium in the§ treatment of bipolar disorder.
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