Ramelteon (TAK-375) Accelerates Reentrainment of Circadian Rhythm after a Phase Advance of the Light-Dark Cycle in Rats

Hirai, Keisuke; Kita, Muneto; Ohta, Hiroyuki; Nishikawa, Hisao; Fujiwara, Yuu; Ohkawa, Shigenori; Miyamoto, Masaomi

doi:10.1177/0748730404269890

Cited by 85 publications

(54 citation statements)

References 32 publications

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“…Current treatments include chronotheraphy, exposure to bright light, and melatonin/ ramelteon administration (40)(41)(42), which offer varying degrees of effectiveness. Our results indicate that interference with the cGMPrelated pathway might be a useful therapeutical tool, especially for jet-lag symptoms due to eastbound flights.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules

Agostino

Plano

Golombék

2007

Proc. Natl. Acad. Sci. U.S.A.

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Mammalian circadian rhythms are generated by a master clock located in the suprachiasmatic nuclei and entrained by lightactivated signaling pathways. In hamsters, the mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase, cGMP and its related kinase (PKG). It is not completely known whether interference with this pathway affects entrainment of the clock, including adaptation to changing light schedules. Here we report that cGMP-specific phosphodiesterase 5 is present in the hamster suprachiasmatic nuclei, and administration of the inhibitor sildenafil (3.5 mg/kg, i.p.) enhances circadian responses to light and decreases the amount of time necessary for reentrainment after phase advances of the light-dark cycle. These results suggest that sildenafil may be useful for treatment of circadian adaptation to environmental changes, including transmeridian eastbound flight schedules.cGMP phosphodiesterase ͉ resynchronization ͉ suprachiasmatic nuclei ͉ phase advance

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Section: Discussionmentioning

confidence: 99%

Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules

Agostino

Plano

Golombék

2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Re-entrainment to the shifted lightdark (LD) cycles usually takes a long time; however, that could be curtailed by the use of melatonin, scheduled exposure to bright light, etc. (Hirai et al 2005). Exposure of humans to bright light at certain time of the day accelerated the reentrainment of several rhythms and alleviated the jetlag symptoms (Burgess et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Bright photophase accelerates re-entrainment after experimental jetlag in Drosophila

Sinam

Sharma

Thakurdas

et al. 2012

Naturwissenschaften

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The efficacy of bright photophase (BP) in accelerating the re-entrainment of Drosophila biarmipes rhythm following 8 h phase advance and delay of light-dark (LD) cycle was examined by subjecting the flies to 24 h LD cycles with dim photophase (DP) at 30 lx and BP at 300 lx. Re-entrainment was analysed by using the activity onset, activity offset and the duration of activity. Following LD advance or delay, the BP flies re-entrained faster than the DP flies which was attributed to the enhanced zeitgeber strength of BP. Nevertheless, the re-entrainment was a protracted process even in the BP flies since the activity offsets underwent more transients than the activity onsets. Thus, this study demonstrates that the BP accelerates the re-entrainment in D. biarmipes. It, however, also reveals that the re-entrainment is a prolonged process when the activity onset and offset are regarded as the rhythm markers.

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“…To test for a direct effect of melatonin on the SCN, we treated SCN explant cultures from Per2 Luc Clock/+ mice with melatonin or the melatonin receptorspecific agonist, ramelteon (30). In Clock/+ SCN, the circadian period of bioluminescence was shortened by the presence of either melatonin or ramelteon (Fig.…”

Section: Wild Typementioning

confidence: 99%

Genetic suppression of the circadian Clock mutation by the melatonin biosynthesis pathway

Shimomura¹,

Lowrey

Vitaterna³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Most laboratory mouse strains including C57BL/6J do not produce detectable levels of pineal melatonin owing to deficits in enzymatic activity of arylalkylamine N-acetyltransferase (AANAT) and Nacetylserotonin O-methyl transferase (ASMT), two enzymes necessary for melatonin biosynthesis. Here we report that alleles segregating at these two loci in C3H/HeJ mice, an inbred strain producing melatonin, suppress the circadian period-lengthening effect of the Clock mutation. Through a functional mapping approach, we localize mouse Asmt to chromosome X and show that it, and the Aanat locus on chromosome 11, are significantly associated with pineal melatonin levels. Treatment of suprachiasmatic nucleus (SCN) explant cultures from Period2 Luciferase (Per2 Luc ) Clock/+ reporter mice with melatonin, or the melatonin agonist, ramelteon, phenocopies the genetic suppression of the Clock mutant phenotype observed in living animals. These results demonstrate that melatonin suppresses the Clock/+ mutant phenotype and interacts with Clock to affect the mammalian circadian system.C ircadian (from the Latin, meaning about a day) rhythms of biochemistry and physiology are innate to virtually all life forms (1, 2). Cell autonomous circadian pacemakers drive these rhythms and synchronize them each day to environmental cues. In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus contains the central pacemaker that coordinates the local circadian clocks present in tissues throughout the body (3, 4). The molecular clock mechanism within individual cells is composed of transcriptional/translational feedback loops and posttranslational processes (1, 5). The bHLH-PAS transcription factors CLOCK and BMAL1 form the primary loop as they activate transcription of the Period (Per1 and Per2) and Cryptochrome (Cry1 and Cry2) genes (1, 6). The PER and CRY proteins subsequently feed back to abrogate their own transcription by directly inhibiting the CLOCK:BMAL1 complex. A second feedback loop stabilizes the primary loop and is composed of REV-ERBα and RORa, two retinoic acid-related orphan receptors, which repress and activate, respectively, transcription of Bmal1. Whereas approximately a dozen genes involved in this timekeeping system have been identified in mammals, it is clear that other, as-yet unknown genes regulate key properties of circadian rhythms (7,8).The SCN imparts daily entraining signals to circadian clocks in cells of peripheral tissues via neural connections and humoral factors (9, 10). One well-characterized circadian rhythm synchronized by the SCN is the synthesis and release at night of the lipophilic pineal hormone melatonin (11). Light information reaches the mammalian pineal gland through a multisynaptic pathway that begins with intrinsically photosensitive melanopsin-containing retinal ganglion cells, which project to the SCN via the retinohypothalamic tract, and ultimately terminates at sympathetic afferents of the pineal gland (12, 13). Lesions of the SCN abolish the melatonin circadian rhythm (14). Two high-affi...

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Ramelteon (TAK-375) Accelerates Reentrainment of Circadian Rhythm after a Phase Advance of the Light-Dark Cycle in Rats

Cited by 85 publications

References 32 publications

Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules

Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules

Bright photophase accelerates re-entrainment after experimental jetlag in Drosophila

Genetic suppression of the circadian Clock mutation by the melatonin biosynthesis pathway

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