Effect of mefloquine, a gap junction blocker, on circadian period2 gene oscillation in the mouse suprachiasmatic nucleus Ex Vivo

Jinmi Koo, Han Kyoung Choe, Hee Dae Kim, Sung Kook Chun, Gi Hoon Son, Kyungjin Kim

    Research output: Contribution to journalArticlepeer-review

    5 Citations (Scopus)

    Abstract

    Background: In mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN). Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions. Methods: We examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2) gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC) knock-in mice using a real-time bioluminescence measurement system. Results: Administration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms. Conclusion: These findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

    Original languageEnglish
    Pages (from-to)361-370
    Number of pages10
    JournalEndocrinology and Metabolism
    Volume30
    Issue number3
    DOIs
    Publication statusPublished - 2015

    Bibliographical note

    Funding Information:
    This work was supported by grants from the Korea Ministry of Education, Science, and Technology (MEST) through the Brain Research Center of the 21st Century Frontier Research Program (2009K001287), the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2013M3C7A 1056731) and the BK21 Plus program through the National Research Foundation of Korea funded by the Ministry of Education (10Z20130012420).

    Publisher Copyright:
    © 2015 Korean Endocrine Society.

    Keywords

    • Circadian rhythm
    • Gap junctions
    • Mefloquine
    • Per2
    • Real-time bioluminescence
    • Suprachiasmatic nucleus

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology

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