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

Abstract

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...

Photosensitivity to different light intensities in blind and sighted rodents

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Systemic serotonin sulfate in opisthobranch mollusks

“…Thus, hemolymph 5-HT sulfate is most probably originating from the nervous system. In mammals, the 5-HT metabolite/hormone, melatonin, under control of the circadian pacemaker, is released at much higher concentrations during night than day (Nakahara et al 2003). Melatonin is the signal for quiescence in both diurnal and nocturnal animals.…”

Effects of photophase illuminance on locomotor activity, urine production and urinary 6-sulfatoxymelatonin in nocturnal and diurnal South African rodents

“…Interestingly, two relatively different daily rhythms in 6-SMT were observed, but both rhythms appeared to be ultradian. Ultradian patterns of melatonin secretion have previously been observed in humans and in mice, and it has been suggested that two separate oscillators are foundational to these patterns (Wehr et al, 1995;Nakahara et al, 2003). Evidence also suggests that daytime and night-time melatonin are regulated by different processes.…”

“…At night, neurological signals from the superior cervical ganglia stimulate the rise in pineal melatonin production via sympathetic nerves (Moore, 1996;Reiter et al, 2011). In CBA mice, application of tetrodotoxin, a Na + channel blocker, effectively suppresses neurological stimulation of pineal melatonin production by night, but not by day (Nakahara et al, 2003). It has therefore been suggested that daytime melatonin regulation primarily results from endogenous activation inside the pinealocyte (Li et al, 2000).…”