Social stress and glucocorticoids alter PERIOD2 rhythmicity in the liver, but not in the suprachiasmatic nucleus
Open accessAbstract
Circadian (~24 h) rhythms in behavior and physiological functions are under control of an endogenous circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN directly drives some of these rhythms or serves as a coordinator of peripheral oscillators residing in other tissues and organs. Disruption of the circadian organization may contribute to disease, including stress-related disorders. Previous research indicates that the master clock in the SCN is resistant to stress, although it is unclear whether stress affects rhythmicity in other tissues, possibly mediated by glucocorticoids, released in stressful situations. In the present study, we examined the effect of uncontrollable social defeat stress and glucocorticoid hormones on the central and peripheral clocks, respectively in the SCN and liver. Transgenic PERIOD2::LUCIFERASE knock-in mice were used to assess the rhythm of the clock protein PERIOD2 (PER2) in SCN slices and liver tissue collected after 10 consecutive days of social defeat stress. The rhythmicity of PER2 expression in the SCN was not affected by stress exposure, whereas in the liver the expression showed a delayed phase in defeated compared to non-defeated control mice. In a second experiment, brain slices and liver samples were collected from transgenic mice and exposed to different doses of corticosterone. Corticosterone did not affect PER2 rhythm of the SCN samples, but caused a phase shift in PER2 expression in liver samples. This study confirms earlier findings that the SCN is resistant to stress and shows that clocks in the liver are affected by social stress, which might be due to the direct influence of glucocorticoids released from the adrenal gland.
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Mounting evidence suggests that circadian clock genes within the brain, skeletal muscle, adipose tissue, gut, liver and pancreas may play a major role in regulating insulin sensitivity, possibly cooperating with glucocorticoids in controlling circadian variability.
“Similarly, mounting evidence suggests that circadian clock genes within the brain, skeletal muscle, adipose tissue, gut, liver and pancreas (to name a few) may play a major role in regulating insulin sensitivity, possibly cooperating with glucocorticoids in controlling circadian variability ( 2, 73, 74 ).”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [73]
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- Authors
- Ota, S. M., Hut, R. A., Riede, S. J., Crosby, P., Suchecki, D., & Meerlo, P.
- Affiliations
- University of Groningen (NL)
- MRC Laboratory of Molecular Biology (GB)
- Universidade Federal de São Paulo (BR)
- Corresponding author
- Suchecki, D.
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 120
- Pages
- 104683
- ISSN
- 0018-506X (ISSN-L)
- PMC
- PMC7332991
- OpenAlex
- W3000355910
- Cited by
- 27
- References
- 37
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 3
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Hormones and Behavior (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (303449/2015-2)
- Rijksuniversiteit Groningen
- Science and Engineering Faculty, Queensland University of Technology
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- social defeat stress, glucocorticoids, corticosterone, Period2, circadian rhythm, suprachiasmatic nucleus, liver clock, peripheral oscillators, phase shift, stress tolerance, clock gene expression
- MeSH terms
- Adrenal Glands, Animals, Brain, Circadian Rhythm, Corticosterone, Dominance-Subordination, Glucocorticoids, Liver, Male, Mice, Inbred C57BL, Mice, Transgenic, Social Behavior, Stress, Psychological, Suprachiasmatic Nucleus, Mice, Gene Knock-In Techniques, Period Circadian Proteins
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