Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus

Abstract Circadian rhythms in clock genes, Bmal1 and Per2 expression were monitored simultaneously in the cultured slice of mouse suprachiasmatic nucleus (SCN) by dual bioluminescent reporters. In the neonatal SCN, the phase-relation between the Bmal1 and Per2 rhythms were significantly changed duri...

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Autores principales:	Shinya Nishide, Sato Honma, Ken-ichi Honma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Per2 Rhythm Rhythmic Bmal1 Per2 Expression Circadian Period Phase-dependent Phase Shifts Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c772267b627a443a9dc921312ec279ef
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spelling	oai:doaj.org-article:c772267b627a443a9dc921312ec279ef2021-12-02T15:08:02ZTwo coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus10.1038/s41598-018-32516-w2045-2322https://doaj.org/article/c772267b627a443a9dc921312ec279ef2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32516-whttps://doaj.org/toc/2045-2322Abstract Circadian rhythms in clock genes, Bmal1 and Per2 expression were monitored simultaneously in the cultured slice of mouse suprachiasmatic nucleus (SCN) by dual bioluminescent reporters. In the neonatal SCN, the phase-relation between the Bmal1 and Per2 rhythms were significantly changed during culture. Medium exchange produced phase-dependent phase shifts (PRCm) in the Bmal1 rhythms, but not in the Per2 rhythms. As a result, the two circadian rhythms were temporally dissociated after medium exchange. In the adult SCN, the phase-relation between the two rhythms was kept constant during culture at least up to 20 cycles. The amplitude of PRCm in the adult SCN was significantly attenuated in the Bmal1 rhythm, whereas a PRCm was developed in the Per2 rhythm. The circadian period was not systematically affected by medium exchange in either of rhythms, regardless of whether it was in the neonatal or the adult SCN. Tetrodotoxin, a sodium channel blocker, enhanced the phase-response in both rhythms but abolished the phase-dependency. In addition, tetrodotoxin lengthened the circadian period independent of the phase of administration. Thus, the Bmal1 and Per2 rhythms in the SCN are dissociable and likely regulated by distinct circadian oscillators. Bmal1 is the component of a Bmal1/REV-ERBa/ROR loop and Per2 a Per/Cry/BMAL1/CLOCK loop. Both loops could be molecular mechanisms of the two circadian oscillators that are coupled through the protein product of Bmal1. The coupling strength between the two oscillations depends on developmental stages.Shinya NishideSato HonmaKen-ichi HonmaNature PortfolioarticlePer2 RhythmRhythmic Bmal1Per2 ExpressionCircadian PeriodPhase-dependent Phase ShiftsMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Per2 Rhythm Rhythmic Bmal1 Per2 Expression Circadian Period Phase-dependent Phase Shifts Medicine R Science Q
spellingShingle	Per2 Rhythm Rhythmic Bmal1 Per2 Expression Circadian Period Phase-dependent Phase Shifts Medicine R Science Q Shinya Nishide Sato Honma Ken-ichi Honma Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus
description	Abstract Circadian rhythms in clock genes, Bmal1 and Per2 expression were monitored simultaneously in the cultured slice of mouse suprachiasmatic nucleus (SCN) by dual bioluminescent reporters. In the neonatal SCN, the phase-relation between the Bmal1 and Per2 rhythms were significantly changed during culture. Medium exchange produced phase-dependent phase shifts (PRCm) in the Bmal1 rhythms, but not in the Per2 rhythms. As a result, the two circadian rhythms were temporally dissociated after medium exchange. In the adult SCN, the phase-relation between the two rhythms was kept constant during culture at least up to 20 cycles. The amplitude of PRCm in the adult SCN was significantly attenuated in the Bmal1 rhythm, whereas a PRCm was developed in the Per2 rhythm. The circadian period was not systematically affected by medium exchange in either of rhythms, regardless of whether it was in the neonatal or the adult SCN. Tetrodotoxin, a sodium channel blocker, enhanced the phase-response in both rhythms but abolished the phase-dependency. In addition, tetrodotoxin lengthened the circadian period independent of the phase of administration. Thus, the Bmal1 and Per2 rhythms in the SCN are dissociable and likely regulated by distinct circadian oscillators. Bmal1 is the component of a Bmal1/REV-ERBa/ROR loop and Per2 a Per/Cry/BMAL1/CLOCK loop. Both loops could be molecular mechanisms of the two circadian oscillators that are coupled through the protein product of Bmal1. The coupling strength between the two oscillations depends on developmental stages.
format	article
author	Shinya Nishide Sato Honma Ken-ichi Honma
author_facet	Shinya Nishide Sato Honma Ken-ichi Honma
author_sort	Shinya Nishide
title	Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus
title_short	Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus
title_full	Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus
title_fullStr	Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus
title_full_unstemmed	Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus
title_sort	two coupled circadian oscillations regulate bmal1-eluc and per2-slr2 expression in the mouse suprachiasmatic nucleus
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/c772267b627a443a9dc921312ec279ef
work_keys_str_mv	AT shinyanishide twocoupledcircadianoscillationsregulatebmal1elucandper2slr2expressioninthemousesuprachiasmaticnucleus AT satohonma twocoupledcircadianoscillationsregulatebmal1elucandper2slr2expressioninthemousesuprachiasmaticnucleus AT kenichihonma twocoupledcircadianoscillationsregulatebmal1elucandper2slr2expressioninthemousesuprachiasmaticnucleus
_version_	1718388280562548736

Two coupled circadian oscillations regulate Bmal1-ELuc and Per2-SLR2 expression in the mouse suprachiasmatic nucleus

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