title: Chronic stress affects PERIOD2 expression through glycogen synthase kinase-3β phosphorylation in the central clock.
abstract: Mood disorders are considered to be associated with altered circadian rhythms, but the correlation between them has remained obscure. The mood stabilizer, lithium, is an inhibitor of glycogen synthase kinase-3β (GSK-3β), which is a modulator of the circadian clock system. Here, we show that chronic restraint (CR) stress diminishes behavioral activity and rhythmicity in mice. CR stress elevated GSK-3β phosphorylation and blunted the rhythmic expression of PERIOD2 (PER2) in the brain. Moreover, lithium, when administered to the stress-imposed mice, reduced GSK-3β phosphorylation and restored PER2 expression in the suprachiasmatic nucleus in a nighttime-specific manner. These data suggest that CR stress altered the circadian behavioral rhythm through a change in circadian gene expression of PER2 and GSK-3β phosphorylation in the suprachiasmatic nucleus.
authors.affiliation: Department of Pharmacology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Kinoshita
authors.forename: Koyomi
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Norio
authors.initials: N
authors.lastname: Ishida
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D057906:Circadian Clocks / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D018020:Lithium Compounds / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D056950:Period Circadian Proteins / Q000096:biosynthesis*; D010766:Phosphorylation; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D018020:Lithium Compounds; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3