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Original Article
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
Endocrinol Metab. 2015;30(3):361-370.   Published online December 9, 2014
DOI: https://doi.org/10.3803/EnM.2015.30.3.361
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  • 5 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   
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.

Citations

Citations to this article as recorded by  
  • High-Throughput Screening Assay for Detecting Drug-Induced Changes in Synchronized Neuronal Oscillations and Potential Seizure Risk Based on Ca2+ Fluorescence Measurements in Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neuronal 2D and 3D Cultures
    Hua-Rong Lu, Manabu Seo, Mohamed Kreir, Tetsuya Tanaka, Rie Yamoto, Cristina Altrocchi, Karel van Ammel, Fetene Tekle, Ly Pham, Xiang Yao, Ard Teisman, David J. Gallacher
    Cells.2023; 12(6): 958.     CrossRef
  • The role of gap junctions in cell death and neuromodulation in the retina
    Gergely Szarka, Márton Balogh, ÁdámJ Tengölics, Alma Ganczer, Béla Völgyi, Tamás Kovács-Öller
    Neural Regeneration Research.2021; 16(10): 1911.     CrossRef
  • Programming effects of maternal stress on the circadian system of adult offspring
    Seongsik Yun, Eun Jeong Lee, Han Kyoung Choe, Gi Hoon Son, Kyungjin Kim, Sooyoung Chung
    Experimental & Molecular Medicine.2020; 52(3): 473.     CrossRef
  • Kisspeptin Neuron-Specific and Self-Sustained Calcium Oscillation in the Hypothalamic Arcuate Nucleus of Neonatal Mice: Regulatory Factors of its Synchronization
    Doyeon Kim, Sangwon Jang, Jeongah Kim, Inah Park, Kyojin Ku, Mijung Choi, Sukwon Lee, Won Do Heo, Gi Hoon Son, Han Kyoung Choe, Kyungjin Kim
    Neuroendocrinology.2020; 110(11-12): 1010.     CrossRef
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