Social stress and glucocorticoids alter PERIOD2 rhythmicity in the liver, but not in the suprachiasmatic nucleus

• Published in: Hormones and behavior Vol. 120; p. 104683
• Main Authors: Ota, S.M., Hut, R.A., Riede, S.J., Crosby, P., Suchecki, D., Meerlo, P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2020; Academic Press
• Subjects: Adrenal Glands - metabolism; Animals; Brain - drug effects; Brain - metabolism; Circadian disruption; Circadian Rhythm - drug effects; Circadian Rhythm - genetics; Circadian Rhythm - physiology; Clock gene expression; Corticosterone - metabolism; Dominance-Subordination; Gene Knock-In Techniques; Glucocorticoids; Glucocorticoids - pharmacology; Liver - drug effects; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Period Circadian Proteins - genetics; Period Circadian Proteins - metabolism; Peripheral oscillator; Social Behavior; Social stress; Stress, Psychological - genetics; Stress, Psychological - metabolism; Stress, Psychological - physiopathology; Suprachiasmatic nucleus; Suprachiasmatic Nucleus - drug effects; Suprachiasmatic Nucleus - metabolism; Suprachiasmatic nucleus; Peripheral oscillator; Circadian disruption; Clock gene expression; Social stress; Glucocorticoids
• ISSN: 0018-506X; 1095-6867
• DOI: 10.1016/j.yhbeh.2020.104683

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.
•Chronic social defeat does not affect phase or period of the circadian rhythm.•Chronic social defeat does not alter PER2 expression in the suprachiasmatic nucleus.•Chronic social defeat phase shifts PER2 expression in the liver.•PER2 expression in the liver is altered by corticosterone in vitro.