Daily cycles of active GSK3 proteins influence the timing of clock genes in the brain's master clock

Significant circadian rhythmicity of phosphorylated GSK3 (α and β) was observed in the suprachiasmatic nucleus of mice.

• Chronic activation of GSK3 isoforms impaired the rhythmic expression of the target protein BMAL1.
• Pharmacological inhibition of GSK3 with 20 µM CHIR-99021 enhanced the amplitude and shortened the period of PER2::luciferase rhythms in tissue cultures.
• GSK3 activity may be regulated by the circadian clock, suggesting a feedback mechanism that influences the molecular clock in the suprachiasmatic nucleus.

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