Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo.
10.3803/EnM.2015.30.3.361
- Author:
Jinmi KOO
1
;
Han Kyoung CHOE
;
Hee Dae KIM
;
Sung Kook CHUN
;
Gi Hoon SON
;
Kyungjin KIM
Author Information
1. Department of Biological Sciences and Brain Research Center for 21st Frontier Program in Neuroscience, Seoul National University College of Natural Sciences, Seoul, Korea. kyungjin@dgist.ac.kr
- Publication Type:Original Article
- Keywords:
Circadian rhythm;
Suprachiasmatic nucleus;
Gap junctions;
Per2;
Real-time bioluminescence;
Mefloquine
- MeSH:
Animals;
Circadian Rhythm;
Electrical Synapses;
Gap Junctions*;
Hypothalamus;
Luminescent Measurements;
Mammals;
Mefloquine*;
Mice*;
Neurons;
Phase Transition;
Suprachiasmatic Nucleus*
- From:Endocrinology and Metabolism
2015;30(3):361-370
- CountryRepublic of Korea
- Language:English
-
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.
