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Glycogen synthase kinase-3β haploinsufficiency lengthens the circadian locomotor activity period in mice.

Publication Type:

Journal Article

Source:

Behav Brain Res, Volume 253, p.262-5 (2013)

Keywords:

Animals, Circadian Rhythm, Glycogen Synthase Kinase 3, Haploinsufficiency, Male, Mice, Mice, Knockout, Motor Activity, Suprachiasmatic Nucleus

Abstract:

<p>The mood stabiliser drug lithium has been reported to impact circadian rhythms in vertebrates. Among several putative therapeutic molecular targets, direct inhibition of glycogen synthase kinase-3 beta (GSK3β) by lithium has been proposed to underlie its effects on circadian physiology. Here we study the effect of GSK3β haploinsufficiency on the circadian locomotor activity in mice during a free-running period in comparison to wildtype littermates (WT). Mice were housed individually to record their circadian wheel running activity and were entrained to a 12h light/12h dark cycle for 14 days and then placed under constant darkness for 14 days to allow free-running. During the free-running phase, the circadian locomotor activity period of GSK3β(+/-) was significantly lengthened (23.83±0.05h) when compared to the WT mice (23.54±0.10h; p=0.0374). No significant difference in locomotor activity was observed. Knowing that GSK3β interacts with most of the core clock components, these data suggest that GSK3β acts as a critical intrinsic regulator of the circadian clock and plays an important role in regulating its period in response to lithium treatment.</p>

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