Most cited article - PubMed ID 25828914
Acute morphine affects the rat circadian clock via rhythms of phosphorylated ERK1/2 and GSK3β kinases and Per1 expression in the rat suprachiasmatic nucleus
The circadian clock in the suprachiasmatic nucleus (SCN) regulates daily rhythms in physiology and behaviour and is an important part of the mammalian homeostatic system. Previously, we have shown that systemic inflammatory stimulation with lipopolysaccharide (LPS) induced the daytime-dependent phosphorylation of STAT3 in the SCN. Here, we demonstrate the LPS-induced Stat3 mRNA expression in the SCN and show also the circadian rhythm in Stat3 expression in the SCN, with high levels during the day. Moreover, we examined the effects of LPS (1mg/kg), applied either during the day or the night, on the rhythm in locomotor activity of male Wistar rats. We observed that recovery of normal locomotor activity patterns took longer when the animals were injected during the night. The clock genes Per1, Per2 and Nr1d1, and phosphorylation of kinases ERK1/2 and GSK3β are sensitive to external cues and function as the molecular entry for external signals into the circadian clockwork. We also studied the immediate changes in these clock genes expressions and the phosphorylation of ERK1/2 and GSK3β in the suprachiasmatic nucleus in response to daytime or night-time inflammatory stimulation. We revealed mild and transient changes with respect to the controls. Our data stress the role of STAT3 in the circadian clock response to the LPS and provide further evidence of the interaction between the circadian clock and immune system.
- MeSH
- Circadian Rhythm drug effects MeSH
- Rats MeSH
- Lipopolysaccharides toxicity MeSH
- Locomotion drug effects MeSH
- MAP Kinase Signaling System drug effects MeSH
- Mitogen-Activated Protein Kinase 3 metabolism MeSH
- Suprachiasmatic Nucleus metabolism pathology MeSH
- Rats, Wistar MeSH
- Gene Expression Regulation drug effects MeSH
- STAT3 Transcription Factor biosynthesis MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Lipopolysaccharides MeSH
- Mitogen-Activated Protein Kinase 3 MeSH
- Stat3 protein, rat MeSH Browser
- STAT3 Transcription Factor MeSH
The intrinsic period of circadian clock in the suprachiasmatic nucleus is entrained to a 24-h cycle by external cues, mainly light. Previous studies have shown that light applied at night induces robust phosphorylation of extracellular-signal-regulated kinase that is necessary to process the light pulse into the phase shift of the clock phase. In this study, we show the persistent downregulation of phosphorylated extracellular-signal-regulated kinase and transient downregulation of phosphorylated glycogen synthase kinase-3beta in the ventrolateral part of the suprachiasmatic nucleus to photic stimuli starting at 2 h after the beginning of the light pulse. As both kinases are involved in regulation of circadian clockwork, we hypothesize that these changes may contribute to the phase-shifting effect of light at night.
- MeSH
- Circadian Clocks * MeSH
- Glycogen Synthase Kinase 3 metabolism MeSH
- Glycogen Synthase Kinase 3 beta MeSH
- Rats MeSH
- MAP Kinase Signaling System MeSH
- Mitogen-Activated Protein Kinase 1 metabolism MeSH
- Mitogen-Activated Protein Kinase 3 metabolism MeSH
- Suprachiasmatic Nucleus metabolism physiology MeSH
- Rats, Wistar MeSH
- Reaction Time * MeSH
- Photic Stimulation MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Gsk3b protein, rat MeSH Browser
- Glycogen Synthase Kinase 3 MeSH
- Glycogen Synthase Kinase 3 beta MeSH
- Mitogen-Activated Protein Kinase 1 MeSH
- Mitogen-Activated Protein Kinase 3 MeSH