Resetting central and peripheral circadian oscillators in transgenic rats
Abstract
In multicellular organisms, circadian oscillators are organized into multitissue systems which function as biological clocks that regulate the activities of the organism in relation to environmental cycles and provide an internal temporal framework. To investigate the organization of a mammalian circadian system, we constructed a transgenic rat line in which luciferase is rhythmically expressed under the control of the mouse Per1 promoter. Light emission from cultured suprachiasmatic nuclei (SCN) of these rats was invariably and robustly rhythmic and persisted for up to 32 days in vitro. Liver, lung, and skeletal muscle also expressed circadian rhythms, which damped after two to seven cycles in vitro. In response to advances and delays of the environmental light cycle, the circadian rhythm of light emission from the SCN shifted more rapidly than did the rhythm of locomotor behavior or the rhythms in peripheral tissues. We hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily lost following large, abrupt shifts in the environmental light cycle.
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There is evidence that peripheral clocks in metabolically relevant tissues shift at a slower rate than the central circadian pacemaker.
“In addition, there is evidence that peripheral clocks in metabolically relevant tissues shift at a slower rate than the central circadian pacemaker (30).”
From Circadian Misalignment Augments Markers of Insulin Resistance and Inflammation, Independently of Sleep Loss (2014) · cites this paper as [30]
The circadian rhythm exists even at the organ level in culture and at the cellular level.
“It has been shown that the circadian rhythm exists even at the organ level in the culture and the cellular level (48, 49).”
From Modeling the hypothalamus-pituitary-adrenal axis: A review and extension (2015) · cites this paper as [48]
Circadian oscillators are present in peripheral tissues such as liver, heart, lung, skeletal muscle, and adrenal glands.
“circadian oscillators have been found in a number of peripheral tissues, such as liver, heart, lung, skeletal muscle, and adrenal glands [2, 3].”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [3]
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Visualizing jet lag in the mouse suprachiasmatic nucleus and peripheral circadian timing system
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A time to remember: The role of circadian clocks in learning and memory.
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Physiological responses to food intake throughout the day
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Circadian rhythms – from genes to physiology and disease
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Bioinformatic Analysis of Circadian Gene Oscillation in Mouse Aorta
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Links between circadian rhythms and psychiatric disease
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- Authors
- Yamazaki, S., Numano, R., Abe, M., Hida, A., Takahashi, R.-I., Ueda, M., Block, G. D., Sakaki, Y., Menaker, M., & Tei, H.
- Affiliations
- University of Virginia (US)
- Institute of Medical Science, The University of Tokyo (JP)
- Y.S. New Technology Institute Inc., 519 Shimoishibashi, Ishibashi-machi, Tochigi, 329-0500, Japan.
- Corresponding author
- Yamazaki, Shin
- Numano, Rika
- Abe, Michikazu
- Menaker, Michael
- Tei, Hajime
- Venue
- Science
- Published
- 2000-04-28
- Volume
- 288
- Issue
- 5466
- Pages
- 682-685
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2035809873
- Cited by
- 1,907
- References
- 16
- Citations by year
- 2026: 34 · 2025: 51 · 2024: 71 · 2023: 53 · 2022: 81 · 2021: 65 · 2020: 81 · 2019: 65 · 2018: 70 · 2017: 62 · 2016: 76 · 2015: 60 · 2014: 82 · 2013: 97 · 2012: 79
- FWCI
- 30.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH056647, MH 56647)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Physical Sciences › Computer Science › Computer Networks and Communications › Nonlinear Dynamics and Pattern Formation
- Keywords
- circadian clock, suprachiasmatic nucleus, peripheral circadian oscillators, luciferase reporter, transgenic rats, circadian entrainment, phase resetting, locomotor rhythm, liver, lung, skeletal muscle, circadian pacemaker
- MeSH terms
- Animals, Biological Clocks, Circadian Rhythm, Darkness, Light, Liver, Luciferases, Lung, Male, Motor Activity, Nuclear Proteins, Promoter Regions, Genetic, Suprachiasmatic Nucleus, Genes, Reporter, Muscle, Skeletal, Cell Cycle Proteins, Animals, Genetically Modified, Culture Techniques, Mice, Rats, Period Circadian Proteins
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