The circadian clock regulates bodily rhythms by time cues that result from the integration of genetically encoded endogenous rhythms with external cycles, most potently with the light/dark cycle. Chronic exposure to constant light in adulthood disrupts circadian system function and can induce behavioral and physiological arrhythmicity with potential clinical consequences. Since the developing nervous system is particularly vulnerable to experiences during the critical period, we hypothesized that early-life circadian disruption would negatively impact the development of the circadian clock and its adult function. Newborn rats were subjected to a constant light of 16 lux from the day of birth through until postnatal day 20, and then they were housed in conditions of L12 h (16 lux): D12 h (darkness). The circadian period was measured by locomotor activity rhythm at postnatal day 60, and the rhythmic expressions of clock genes and tissue-specific genes were detected in the suprachiasmatic nuclei, retinas, and pineal glands at postnatal days 30 and 90. Our data show that early postnatal exposure to constant light leads to a prolonged endogenous period of locomotor activity rhythm and affects the rhythmic gene expression in all studied brain structures later in life.

• Keywords
• circadian clock, light at night, pineal gland, rat, retina, suprachiasmatic nucleus,
• Publication type
• Journal Article MeSH

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