Rapid Resetting of the Mammalian Circadian Clock

Best, Jonathan D.; Maywood, Elizabeth S.; Smith, Karen; Hastings, Michael H.

doi:10.1523/jneurosci.19-02-00828.1999

Cited by 104 publications

(94 citation statements)

References 52 publications

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Section: Discussionmentioning

confidence: 99%

“…MKC-242 has been shown to prolong the light-induced increases in both per1 and per2 mRNA (Takahashi et al, 2002), which normally decay within a few hours (Best et al, 1999;Khammanivong and Nelson, 2000). Since both per mRNA and Per protein levels are correlated with behavioral phase shifting (Best et al, 1999;Masubuchi et al, 2005), it is possible that the greater phase advance to light observed with MKC-242 and NAN-190 may be due to their extended elevation of per, and thus Per protein. Such might be accomplished by allowing enhanced Per production from the lightinduced per mRNA or by affecting the stability of Per protein (which is known to alter phaseshift magnitude) (Gallego et al, 2006;Jakubcakova et al, 2007;Lee et al, 2007;Masubuchi et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

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NAN-190 potentiates the circadian response to light and speeds re-entrainment to advanced light cycles

2008

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Health problems can arise from de-synchrony between the external environment and the endogenous circadian rhythm, yet the circadian system is not able to quickly adjust to large, abrupt changes in the external daily cycle. In this study, we investigated the ability of to potentiate the circadian rhythm response to light as measured by phase of behavioral activity rhythms. (5 mg/kg, i.p.) was able to significantly potentiate the response to light both in dark-adapted and entrained hamsters. Furthermore, was effective even when administered up to 6 hours after light onset. Response to a light pulse was both greater in magnitude and involved fewer unstable transient cycles. Finally, was able to speed re-entrainment to a 6 h advance of the light: dark cycle by an average of 6 days when compared to vehicle-treated animals. This work suggests that compounds like NAN-190 may hold great potential as a pharmaceutical treatment for jetlag, shift work, and other circadian disorders. Keywordsserotonin; circadian; light; rhythm; jet-lag; phase shift; transient; entrainment Circadian rhythms are endogenously generated rhythms that coordinate processes such as hormone release, digestive enzyme secretion, and the sleep/wake cycle. In mammals, the major pacemaker is located in the suprachiasmatic nucleus (SCN) in the brain, which uses environmental cues to synchronize, or entrain, internal rhythms to the external surroundings (Rusak and Zucker, 1979; Ralph et al., 1990). Jetlag occurs when internal circadian rhythms become desynchronized from the external time. In humans, this desynchronization results in acute negative effects such as lowered performance levels on the job, difficulty sleeping at the appropriate times, and gastrointestinal problems. If frequent or prolonged, circadian desynchrony may be associated with more chronic health problems in people such as increased risk of breast cancer, cardiovascular disease, reproductive difficulties and peptic ulcers (Knutsson, 2003;Megdal et al., 2005). Studies using laboratory animals even link jetlag with increased rate of tumor growth and increased mortality in aged mice (Davidson et al., 2006;Filipski et al., 2004). Given the detrimental effects, studies have investigated several different methods to reduce circadian desynchrony. Melatonin, exposure to bright light, and gradual shifting of the sleep/wake cycle prior to jet travel in varying combinations have all been shown *Corresponding author. Tel: 1-413-585-3925; fax: 1-413-585-3786. E-mail address: mharring@email.smith.edu (M. Harrington). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

NAN-190 potentiates the circadian response to light and speeds re-entrainment to advanced light cycles

2008

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“…Resetting of the SCN oscillators is thought to occur rapidly after a light pulse (Best et al, 1999;Watanabe et al, 2001), and significant effort has been devoted to identifying the phenotype of retinorecipient SCN cells. Estimates of the size and identity of this population of light-responsive cells range from 20 to 40% of SCN cells and vary depending on the assay used [electrophysiology (Sawaki, 1979;Meijer et al, 1986;Aggelopoulos and Meissl, 2000) or IEG expression (Earnest et al, 1993;Silver et al, 1996;Castel et al, 1997;Aioun et al, 1998)].…”

Section: Discussionmentioning

confidence: 99%

Phenotype Matters: Identification of Light-Responsive Cells in the Mouse Suprachiasmatic Nucleus

et al. 2004

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“…In this study, we found that melatonin levels displayed a clear phase-advance from the next cycle, although the rhythm of the locomotor activity takes a few more days to exhibit an explicit phase advance. When a phase shift of the clock will be complete after exposure to a light pulse is an important question, and a two-lightpulse paradigm study of locomotor activity strongly suggests that the phase-resetting of the mammalian pacemaker is complete within several hours (33). This has also been supported by a recent finding at the clock gene level showing that the application of N-methyl-D-aspartate, an in vitro counterpart of a light-pulse in behavior, into the SCN slice of transgenic mice carrying the mPer1 promoter driven luciferase gene, induced the phase-shift of the mPer1 transcription rhythm within 2-3 hr (7).…”

Section: Light Induces Immediate Phase Shifts Of Circadian Melatonin mentioning

confidence: 99%

Bimodal circadian secretion of melatonin from the pineal gland in a living CBA mouse

Nakahara

Nakamura

Iigo

et al. 2003

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

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Circadian melatonin secretion is the best-known output signal from the circadian pacemaker in the suprachiasmatic nucleus that indicates internal conditions of the body. We have established a system that enables long-term monitoring of melatonin secretion by implanting a transverse microdialysis probe in or near the pineal gland in a freely moving mouse. This in vivo method enabled continuous measurement of melatonin secretion over a period of >20 days in individual CBA mice, with simultaneous recording of the locomotor activity. Pineal melatonin secretion was completely matched to the circadian change of locomotor activity, and for the light-induced phase shift, the shift of melatonin secretion was clearer than the shift of locomotor rhythm. This analysis allowed us to detect rhythm with a high sensitivity: two peaks of daily secretion were observed, with the first small peak at the day-night transition time and the second large peak at midnight. The large nighttime peak was suppressed by tetrodotoxin, a Na ؉ channel blocker, and enhanced by both phenylephrine and isoproterenol, ␣-and ␤-adrenergic agonists, whereas daytime melatonin levels were not affected by tetrodotoxin infusion. This finding suggests that, in CBA mice, melatonin release at night is activated by adrenergic signaling from the superior cervical ganglion, but the enhancement of melatonin during daytime is not mediated by neuronal signaling.circadian rhythm ͉ locomotor activity ͉ microdialysis I n mammals, most physiological and behavioral events are subject to well controlled daily oscillations, and these rhythms are generated by the circadian clock in the suprachiasmatic nucleus (SCN) (1, 2). Recent progress in the genetic dissection of the clock genes has provided an outline of the molecular machinery of clock oscillation: the generation of rhythm begins at the transcription͞ translation feedback loops of clock genes (3-6). The dynamics of this core oscillatory loop is now monitored in transgenic animals carrying the mPer1 promoter driven luciferase reporter (7-9).From the Drosophila to mammals, an astonishing feature in circadian biology is that the rhythm of this gene transcription is integrated to cell, tissue, and organ, and finally to coordinated temporal organization at the system level. Because the molecular monitoring of gene transcription is now available, real-time rhythm-effector analysis is inevitable to clarify the linkage from the molecular oscillator to the effector. Of the circadian effectors, the behavioral sleep-awaking rhythm is the best known, and locomotor activity is used as a noninvasive output showing the clear-cut circadian expression in living mice. However, the behavioral rhythm is only one output of the SCN oscillator, and the real-time nature of the time information with regard to the body system has not been previously addressed.In our search for a measure of the circadian output that indicates internal conditions of the body, we focused on melatonin (N-acetyl5methoxytryptamine), a hormone primarily secreted by t...

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Rapid Resetting of the Mammalian Circadian Clock

Cited by 104 publications

References 52 publications

NAN-190 potentiates the circadian response to light and speeds re-entrainment to advanced light cycles

NAN-190 potentiates the circadian response to light and speeds re-entrainment to advanced light cycles

Phenotype Matters: Identification of Light-Responsive Cells in the Mouse Suprachiasmatic Nucleus

Bimodal circadian secretion of melatonin from the pineal gland in a living CBA mouse

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