Melatonin in mice: rhythms, response to light, adrenergic stimulation, and metabolism

Kennaway, David J.; Voultsios, Athena; Varcoe, Tamara J.; Moyer, Robert W.

doi:10.1152/ajpregu.00360.2001

Cited by 111 publications

(124 citation statements)

References 36 publications

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“…Light pulses are known to instantly suppress the nocturnal melatonin secretion in the rodent pineal tissue (20,27). When the animals in our experiment were exposed to a 15-min light pulse at circadian time (CT) 20, dialysate melatonin levels significantly decreased to basal levels within 2 hr after the start of light exposure (t ϭ 5.13, df ϭ 4, P Ͻ 0.01) (Fig.…”

Section: Circadian Melatonin Secretion Is Clock-controlled and Synchrmentioning

confidence: 80%

“…However, monitoring melatonin in mice can be difficult because most strains of inbred mice have lost the ability or are very poor at synthesizing melatonin (e.g., C57BL͞6, BALB͞c, and ARK). However, two strains, CBA and C3H, that possess the enzymes for melatonin synthesis display a stable and reproducible circadian rhythm (18)(19)(20)(21). However, existing data on mouse melatonin have been obtained from homogenated pineal tissues or peripheral blood, thus making it very difficult to continuously monitor the hormone.…”

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confidence: 99%

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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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Section: Circadian Melatonin Secretion Is Clock-controlled and Synchrmentioning

confidence: 80%

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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“…In mammals, for example, several clock genes regulate circadian gene expression in central and peripheral clock tissues (3)(4)(5)(6)(7)(8)(9), as well as metabolites in the blood (10)(11)(12)(13)(14)(15). Reflecting circadian regulation of such processes, the potency and toxicity of administered drugs depends on an individual's body time (BT) (16)(17)(18)(19)(20)(21)(22).…”

mentioning

confidence: 99%

“…One conventional way to estimate human internal body time is to periodically sample for more than 24 h the level of melatonin or cortisol, which have robust circadian oscillations in the blood (10)(11)(12). Although this strategy directly measures internal body time, it requires labor-intensive constant sampling under controlled environmental conditions to reveal metabolite peaks and rhythms.…”

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confidence: 99%

Human blood metabolite timetable indicates internal body time

Kasukawa

Sugimoto

Hida

et al. 2012

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

196

168

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A convenient way to estimate internal body time (BT) is essential for chronotherapy and time-restricted feeding, both of which use body-time information to maximize potency and minimize toxicity during drug administration and feeding, respectively. Previously, we proposed a molecular timetable based on circadian-oscillating substances in multiple mouse organs or blood to estimate internal body time from samples taken at only a few time points. Here we applied this molecular-timetable concept to estimate and evaluate internal body time in humans. We constructed a 1.5-d reference timetable of oscillating metabolites in human blood samples with 2-h sampling frequency while simultaneously controlling for the confounding effects of activity level, light, temperature, sleep, and food intake. By using this metabolite timetable as a reference, we accurately determined internal body time within 3 h from just two anti-phase blood samples. Our minimally invasive, moleculartimetable method with human blood enables highly optimized and personalized medicine.metabolomics | circadian rhythm | liquid chromatography mass spectrometry | diagnostic tool M any organisms possess a molecular time-keeping mechanism, a circadian clock, which has endogenous, self-sustained oscillations with a period of about 24 h. Circadian regulation of cell activity occurs in diverse biological processes such as electrical activity, gene/protein expression, and concentration of ions and substances (1, 2). In mammals, for example, several clock genes regulate circadian gene expression in central and peripheral clock tissues (3-9), as well as metabolites in the blood (10-15). Reflecting circadian regulation of such processes, the potency and toxicity of administered drugs depends on an individual's body time (BT) (16)(17)(18)(19)(20)(21)(22). Drug delivery according to body time improves the outcome of pharmacotherapy by maximizing potency and minimizing toxicity (23), and administrating drugs at an inappropriate body time can result in severe side effects (22). For example, rhythm disturbances were induced by administration of IFN-α during the early active phase in mice, although unaffected during the early rest phase (22); and the time of administration of two anticancer drugs, adriamycin (6:00 AM) and cisplatin (6:00 PM), made a lower toxicity effect than its antiphasic administration (24). However, several reports showed that internal body time varies by 5-6 h in healthy humans (25, 26) and as much as 10-12 h in shift workers without forced entrainments (27,28). Therefore, for efficient application of body-time drug delivery or "chronotherapy" (16-20) in a clinical setting, a simple and robust method for estimating an individual's internal body time is needed.Additionally, the timing of food intake may contribute to weight gain (29) and metabolic disease (30) because energy regulation and circadian rhythms are molecularly and physiologically intertwined (31-41). For example, mice fed a high-fat diet during a 12-h light phase gain significantly more ...

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“…Dietary preferences (31) as well as metabolic responses to leptin (13) differ between strains and can confound cardiovascular measurements. The metabolism of melatonin is also strain dependent (18), which may impact on circadian cardiovascular rhythms. These factors need to be considered when designing experiments in mice.…”

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confidence: 99%

Mouse gene targeting in cardiovascular physiology

Ehmke

2003

American Journal of Physiology-Regulatory, Integrative and Comp

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Melatonin in mice: rhythms, response to light, adrenergic stimulation, and metabolism

Cited by 111 publications

References 36 publications

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

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

Human blood metabolite timetable indicates internal body time

Mouse gene targeting in cardiovascular physiology

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