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      Steven A. Brown and the synchronization of circadian rhythms by body temperature cycles

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      European Journal of Neuroscience
      Wiley

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          Abstract

          The mammalian circadian timing system has a hierarchical architecture, with a central pacemaker located in the brain's suprachiasmatic nucleus orchestrating rhythms in behaviour and physiology. In cooperation with environmental cycles, it synchronizes the phases of peripheral oscillators operating in most cells of the body. Even cells kept in tissue culture harbour self‐sustained and cell‐autonomous circadian clocks that keep ticking throughout their lifespan. The master pacemaker in the suprachiasmatic nucleus is synchronized primarily by light–dark cycles, whereas peripheral oscillators are phase entrained by a multitude of systemic signalling pathways. These include pathways depending on feeding–fasting cycles, cellular actin polymerization dynamics, endocrine rhythms and, surprisingly, body temperature oscillations. Using tissue culture and murine models, Steve Brown was the first one to demonstrate that shallow rhythms of mammalian body temperature are timing cues ( zeitgebers) for peripheral circadian clocks.

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          Most cited references41

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          Resetting of circadian time in peripheral tissues by glucocorticoid signaling.

          In mammals, circadian oscillators reside not only in the suprachiasmatic nucleus of the brain, which harbors the central pacemaker, but also in most peripheral tissues. Here, we show that the glucocorticoid hormone analog dexamethasone induces circadian gene expression in cultured rat-1 fibroblasts and transiently changes the phase of circadian gene expression in liver, kidney, and heart. However, dexamethasone does not affect cyclic gene expression in neurons of the suprachiasmatic nucleus. This enabled us to establish an apparent phase-shift response curve specifically for peripheral clocks in intact animals. In contrast to the central clock, circadian oscillators in peripheral tissues appear to remain responsive to phase resetting throughout the day.
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            Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus.

            In mammals, circadian oscillators exist not only in the suprachiasmatic nucleus, which harbors the central pacemaker, but also in most peripheral tissues. It is believed that the SCN clock entrains the phase of peripheral clocks via chemical cues, such as rhythmically secreted hormones. Here we show that temporal feeding restriction under light-dark or dark-dark conditions can change the phase of circadian gene expression in peripheral cell types by up to 12 h while leaving the phase of cyclic gene expression in the SCN unaffected. Hence, changes in metabolism can lead to an uncoupling of peripheral oscillators from the central pacemaker. Sudden large changes in feeding time, similar to abrupt changes in the photoperiod, reset the phase of rhythmic gene expression gradually and are thus likely to act through a clock-dependent mechanism. Food-induced phase resetting proceeds faster in liver than in kidney, heart, or pancreas, but after 1 wk of daytime feeding, the phases of circadian gene expression are similar in all examined peripheral tissues.
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              PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues.

              Mammalian circadian rhythms are regulated by the suprachiasmatic nucleus (SCN), and current dogma holds that the SCN is required for the expression of circadian rhythms in peripheral tissues. Using a PERIOD2::LUCIFERASE fusion protein as a real-time reporter of circadian dynamics in mice, we report that, contrary to previous work, peripheral tissues are capable of self-sustained circadian oscillations for >20 cycles in isolation. In addition, peripheral organs expressed tissue-specific differences in circadian period and phase. Surprisingly, lesions of the SCN in mPer2(Luciferase) knockin mice did not abolish circadian rhythms in peripheral tissues, but instead caused phase desynchrony among the tissues of individual animals and from animal to animal. These results demonstrate that peripheral tissues express self-sustained, rather than damped, circadian oscillations and suggest the existence of organ-specific synchronizers of circadian rhythms at the cell and tissue level.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                European Journal of Neuroscience
                Eur J of Neuroscience
                Wiley
                0953-816X
                1460-9568
                July 2024
                June 04 2024
                July 2024
                : 60
                : 2
                : 3891-3900
                Affiliations
                [1 ] Department of Molecular and Cellular Biology, Sciences III University of Geneva Geneva Switzerland
                Article
                10.1111/ejn.16431
                26d00f03-2671-453b-b891-ad3f71b5e42f
                © 2024

                http://creativecommons.org/licenses/by-nc-nd/4.0/

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