RHYTHMSChronic stress affects PERIOD2 expression through glycogen synthase kinase-3β phosphorylation in the central clockKinoshita, Chisatoa,c; Miyazaki, Koyomib; Ishida, Norioc,dAuthor Information aDepartment of Pharmacology, Teikyo University School of Medicine, Itabashi-ku, Tokyo bBiological Clock Research Group, Biomedical Research Institute cIshida Group of Clock Gene, Department of Biomedical Research, National Institute of Advanced Industrial Science and Technology (AIST) dGraduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.neuroreport.com). Correspondence to Dr Norio Ishida, MD, Ishida Group of Clock Gene, Department of Biomedical Research, National Institute of Advanced Industrial Science and Technology, Central 6-5, 1-1-1, Higashi, Tsukuba, Ibaraki 305-8566, Japan Tel: +81 298 616 131; fax: +81 298 619 499; e-mail: [email protected] Received October 20, 2011 Accepted October 23, 2011 NeuroReport: January 25, 2012 - Volume 23 - Issue 2 - p 98-102 doi: 10.1097/WNR.0b013e32834e7ec2 Buy SDC Metrics 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. © 2012 Lippincott Williams & Wilkins, Inc.