Glycogen synthase kinase 3, circadian rhythms, and bipolar disorder
Subtitle: a molecular link in the therapeutic action of lithium.
Published: 2005
Language: eng
Number of pages: 85
Description: Bipolar disorder (BPD) is characterized by recurring states of mania and depression. In addition to mood imbalances, subjects often suffer from circadian disturbances. Glycogen synthase kinase 3 (GSK3), an essential kinase with widespread roles in development, cell survival, and metabolism has been demonstrated to be an essential component of the Drosophila  circadian clock. These results demonstrate that genetic depletion of GSK3 in synchronized mouse embryonic fibroblasts results in a significant delay in the cycling period of mPer2. Furthermore, pharmacological inhibition of GSK3 activity by Kenpaullone, a known antagonist of GSK3 activity, as well as by lithium, a direct inhibitor of GSK3 and the most common treatment for BPD, induces a phase delay in clock gene transcriptional profiles that phenocopies GSK3 knockdown. These results confirm GSK3 as a plausible target of lithium action in BPD therapeutics, and suggest the circadian clock mechanism as a significant modulator of lithium's clinical benefits.
Notes: Source: Masters Abstracts International, Volume: 44-02, page: 0763.

Thesis (M.Sc.)--University of Toronto, 2005.

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