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Resetting central and peripheral circadian oscillators in transgenic rats
1NSF Center for Biological Timing and Department of Biology, University of Virginia, Charlottesville, VA 22903-2477, USA.
Science (New York, N.Y.)
|April 28, 2000
Summary
This study reveals how the mammalian biological clock in the suprachiasmatic nucleus (SCN) synchronizes peripheral tissues. The SCN clock adjusts faster to light changes than clocks in organs like the liver, ensuring coordinated daily rhythms.
Area of Science:
- Chronobiology
- Mammalian Physiology
- Molecular Biology
Background:
- Multicellular organisms possess integrated circadian systems functioning as biological clocks.
- These clocks regulate organismal activities in response to environmental cycles, providing temporal organization.
- The organization and entrainment mechanisms of mammalian circadian systems remain incompletely understood.
Purpose of the Study:
- To investigate the organizational principles of the mammalian circadian system.
- To characterize the dynamic relationship between the central circadian pacemaker and peripheral oscillators.
- To examine the adaptive capacity of the circadian system to environmental light cycle shifts.
Main Methods:
- Construction of a transgenic rat line expressing luciferase under the Per1 promoter for real-time monitoring of circadian rhythmicity.
- In vitro culture of suprachiasmatic nuclei (SCN) and peripheral tissues (liver, lung, skeletal muscle) to assess rhythm persistence.
- Analysis of circadian rhythm shifts in response to simulated advances and delays in the environmental light cycle.
Main Results:
- Cultured rat SCN exhibited robust, persistent circadian rhythmicity of light emission for up to 32 days.
- Peripheral tissues (liver, lung, skeletal muscle) also showed circadian rhythms, but these damped within 2-7 cycles in vitro.
- The SCN circadian rhythm demonstrated faster phase adjustment to light cycle shifts compared to locomotor behavior and peripheral tissue rhythms.
Conclusions:
- The suprachiasmatic nucleus (SCN) acts as a self-sustained circadian pacemaker, entraining peripheral oscillators.
- Peripheral circadian rhythms are less robust and slower to adapt to environmental changes than the central SCN clock.
- Abrupt, large shifts in the light-dark cycle can temporarily disrupt the SCN's ability to maintain adaptive phase control in peripheral tissues.
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