Bipolar disorder: leads from the molecular and
cellular mechanisms of action of mood stabilizers

Manji HK, Moore GJ, Chen G.
Laboratory of Molecular Pathophysiology,
Wayne State University School of Medicine,
Detroit, Michigan, USA.
Br J Psychiatry Suppl 2001 Jun;41:s107-19


BACKGROUND: New research is dramatically altering our understanding of the molecular mechanisms underlying neuronal communication. AIM: To elucidate the molecular mechanisms underlying the therapeutic effects of mood stabilizers. METHOD: Results from integrated clinical and laboratory studies are reviewed. RESULTS: Chronic administration of lithium and valproate produced a striking reduction in protein kinase C (PKC) isozymes in rat frontal cortex and hippocampus. In a small study, tamoxifen (also a PKC inhibitor) had marked antimanic efficacy. Both lithium and valproate regulate the DNA binding activity of the activator protein I family of transcription factors. Using mRNA differential display, it was also shown that chronic administration of lithium and valproate modulates expression of several genes. An exciting finding is that of a robust elevation in the levels of the cytoprotective protein, bcl-2. CONCLUSIONS: The results suggest that regulation of signalling pathways may play a major part in the long-term actions of mood stabilizers. Additionally, mood stabilizers may exert underappreciated neuroprotective effects.
Unipolar mania
Protein kinases
Protein kinase C
Bipolar disorders
Drugs for bipolars
Lithium prophylaxis
The manic spectrum
Bipolar polypharmacy
The many faces of mania
The ERK signaling cascade
The protein kinase C cascade
Mania: lithium versus divaplroex

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