title: Glycogen synthase kinase-3β haploinsufficiency lengthens the circadian locomotor activity period in mice.
abstract: 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.
authors.affiliation: Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec, Behavioral Platform, Quebec City, Quebec, Canada.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Lavoie
authors.forename: Marc
authors.initials: M
authors.lastname: Hébert
authors.forename: Jean-Martin
authors.initials: JM
authors.lastname: Beaulieu
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D057895:Haploinsufficiency / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics* / Q000502:physiology; D013493:Suprachiasmatic Nucleus
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3
keywords: Circadian rhythms; Free-running; Glycogen synthase kinase-3β; Locomotor activity; Period