Chronic stress affects PERIOD2 expression through glycogen synthase kinase-3β phosphorylation in the central clock

Neuroreport. 2012 Jan 25;23(2):98-102. doi: 10.1097/WNR.0b013e32834e7ec2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Brain / drug effects
  • Brain / metabolism*
  • Circadian Clocks / physiology*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Lithium Compounds / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Period Circadian Proteins / biosynthesis*
  • Phosphorylation
  • Stress, Psychological / metabolism*

Substances

  • Antidepressive Agents
  • Lithium Compounds
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3