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

S.M Ota,R.A Hut,S.J Riede,P Crosby,D Suchecki,P Meerlo

doi:10.1016/j.yhbeh.2020.104683

Abstract

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.

Highlights

Circadian (~24 h) rhythms in physiology and behavior are the result of interacting endogenous rhythms that reside in most, if not every cell in the body (Dibner et al, 2010; Leise et al, 2012, Saper, 2013; Yoo et al, 2004)
The aims of the present study were to determine whether chronic social stress would affect the suprachiasmatic nucleus (SCN) and/or the peripheral liver clock, and if that was the case, whether the glucocorticoid hormone corticosterone played a role on the stress effects
In agreement with the results for the activity rhythm was the finding that the rhythm of PER2 in the SCN collected after the stress period was unaffected by defeat

Summary

Introduction

Circadian (~24 h) rhythms in physiology and behavior are the result of interacting endogenous rhythms that reside in most, if not every cell in the body (Dibner et al, 2010; Leise et al, 2012, Saper, 2013; Yoo et al, 2004) These rhythms persist even in isolated tissues and in the absence of environmental cycles that could drive them, e.g. in liver, lung, kidney and pituitary (Yamazaki et al, 2000; Yoo et al, 2004). The circadian system provides a precise internal time-of-day-representation that aids optimal timing of physiological processes and behavior in rhythmic environments (Dibner et al, 2010)

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