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The choroid plexus is an important circadian clock component

Author

Listed:
  • Jihwan Myung

    (RIKEN Brain Science Institute (BSI)
    Okinawa Institute of Science and Technology
    Taipei Medical University
    Taipei Medical University)

  • Christoph Schmal

    (Charité-Universitätsmedizin and Humboldt Universität)

  • Sungho Hong

    (Okinawa Institute of Science and Technology)

  • Yoshiaki Tsukizawa

    (Hiroshima University School of Medicine)

  • Pia Rose

    (Charité-Universitätsmedizin and Humboldt Universität)

  • Yong Zhang

    (Washington University School of Medicine)

  • Michael J. Holtzman

    (Washington University School of Medicine)

  • Erik De Schutter

    (Okinawa Institute of Science and Technology)

  • Hanspeter Herzel

    (Charité-Universitätsmedizin and Humboldt Universität)

  • Grigory Bordyugov

    (Charité-Universitätsmedizin and Humboldt Universität)

  • Toru Takumi

    (RIKEN Brain Science Institute (BSI)
    Hiroshima University School of Medicine)

Abstract

Mammalian circadian clocks have a hierarchical organization, governed by the suprachiasmatic nucleus (SCN) in the hypothalamus. The brain itself contains multiple loci that maintain autonomous circadian rhythmicity, but the contribution of the non-SCN clocks to this hierarchy remains unclear. We examine circadian oscillations of clock gene expression in various brain loci and discovered that in mouse, robust, higher amplitude, relatively faster oscillations occur in the choroid plexus (CP) compared to the SCN. Our computational analysis and modeling show that the CP achieves these properties by synchronization of “twist” circadian oscillators via gap-junctional connections. Using an in vitro tissue coculture model and in vivo targeted deletion of the Bmal1 gene to silence the CP circadian clock, we demonstrate that the CP clock adjusts the SCN clock likely via circulation of cerebrospinal fluid, thus finely tuning behavioral circadian rhythms.

Suggested Citation

  • Jihwan Myung & Christoph Schmal & Sungho Hong & Yoshiaki Tsukizawa & Pia Rose & Yong Zhang & Michael J. Holtzman & Erik De Schutter & Hanspeter Herzel & Grigory Bordyugov & Toru Takumi, 2018. "The choroid plexus is an important circadian clock component," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03507-2
    DOI: 10.1038/s41467-018-03507-2
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    Cited by:

    1. Carolin Ector & Christoph Schmal & Jeff Didier & Sébastien De Landtsheer & Anna-Marie Finger & Francesca Müller-Marquardt & Johannes H. Schulte & Thomas Sauter & Ulrich Keilholz & Hanspeter Herzel & A, 2024. "Time-of-day effects of cancer drugs revealed by high-throughput deep phenotyping," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Xu, Yan & Gu, Changgui & Wang, Jiangsheng & Wang, Man & Wang, Haiying & Yang, Huijie & Song, Yuxuan, 2023. "Goodwin oscillator model explains different response of circadian rhythms to constant light," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 618(C).
    3. Ryann M. Fame & Peter N. Kalugin & Boryana Petrova & Huixin Xu & Paul A. Soden & Frederick B. Shipley & Neil Dani & Bradford Grant & Aja Pragana & Joshua P. Head & Suhasini Gupta & Morgan L. Shannon &, 2023. "Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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