Amplitude Of Melatonin Rhythm Research Articles

Is Idiopathic Hypersomnia a Circadian Rhythm Disorder?

The pathophysiology of idiopathic hypersomnia remains unclear, but some of its clinical features suggest the possibility of circadian dysfunction. This review will provide an overview of recent studies of circadian biology that have begun to elucidate the potential role of circadian rhythm dysfunction in idiopathic hypersomnia. Clinically, people with idiopathic hypersomnia tend to have both a late chronotype and prominent sleep inertia or sleep drunkenness. Melatonin and cortisol profiles in people with IH confirm this tendency toward phase delay. More recently, it has been suggested that the night phase as defined by melatonin profile or period length as defined by BMA1 in dermal fibroblasts may also be prolonged in people with IH. Additionally, amplitude of melatonin rhythm and circadian gene expression, particularly BMAL1, PER1, and PER2, may be impaired in this disease. Clinical features, melatonin profiles, and circadian gene expression all suggest abnormalities of the circadian system may be a contributor to the pathogenesis of IH.

60 YEARS OF NEUROENDOCRINOLOGY: Regulation of mammalian neuroendocrine physiology and rhythms by melatonin.

The isolation of melatonin was first reported in 1958. Since the demonstration that pineal melatonin synthesis reflects both daily and seasonal time, melatonin has become a key element of chronobiology research. In mammals, pineal melatonin is essential for transducing day-length information into seasonal physiological responses. Due to its lipophilic nature, melatonin is able to cross the placenta and is believed to regulate multiple aspects of perinatal physiology. The endogenous daily melatonin rhythm is also likely to play a role in the maintenance of synchrony between circadian clocks throughout the adult body. Pharmacological doses of melatonin are effective in resetting circadian rhythms if taken at an appropriate time of day, and can acutely regulate factors such as body temperature and alertness, especially when taken during the day. Despite the extensive literature on melatonin physiology, some key questions remain unanswered. In particular, the amplitude of melatonin rhythms has been recently associated with diseases such as type 2 diabetes mellitus but understanding of the physiological significance of melatonin rhythm amplitude remains poorly understood.

Like melatonin, agomelatine (S20098) increases the amplitude of oscillations of two clock outputs: melatonin and temperature rhythms

Depression and biological rhythms disturbances are strongly associated. Agomelatine is an antidepressant with melatoninergic MT1-MT2 agonist and serotoninergic 5-HT2c antagonist properties. Both melatonin and 5-HT are known to modulate circadian rhythmicity controlled by the endogenous clock located in the suprachiasmatic nuclei (SCN). The aim of the present study was to compare the effect of an acute injection of agomelatine (Ago), melatonin (MLT) or an antagonist 5-HT2c (S32006), on the rhythms of two robust clock outputs: the pineal MLT secretion and the body temperature rhythm (Tc). Daily endogenous MLT profiles were measured using transpineal microdialysis over 4 consecutive days in rats maintained on a 12 h light/12 h dark cycle. Simultaneously, Tc was recorded. The drugs were injected subcutaneously at three doses (1, 2.5 or 5 mg/kg) at the onset of darkness. Both Ago and MLT, at the dose of 2.5 mg/kg, increased the amplitude of the peak of MLT secretion and this effect was observed 2 d after injection. Moreover, both drugs induced a dose-dependent advance of the rhythm onset which resulted in lengthening of the MLT peak. S32006 had no effect on the rhythm of MLT. Ago, MLT and S32006 increased the amplitude of the rhythm of Tc. These data suggest a central action of Ago, directly on the SCN, via melatoninergic receptors responsible for both the increased amplitude of MLT rhythm and the phase advance. The increase in the amplitude of the body temperature could involve both MLT agonist and/or 5-HT2c antagonist properties of Ago.

Pineal melatonin synthesis is decreased in type 2 diabetic Goto–Kakizaki rats

Aims It is not well understood why the amplitude of melatonin rhythms is reduced in diabetic animals and humans. This paper addresses the differences in the pineal melatonin synthesis of type 2 diabetic Goto–Kakizaki (GK) rats compared to non-diabetic Wistar rats (8 and 50 weeks old). Main methods Plasma melatonin concentrations and the pineal content of melatonin and its precursors (tryptophan, 5-hydroxytryptophan, serotonin, and N-acetylserotonin) were quantified at the middle of the day and night. Additionally, the expression of melatonin synthesizing enzymes, pineal noradrenaline content, and pineal protein content were considered, and the melatonin secreting capacity of pineal glands was studied in vitro. Key findings The pineal glands of diabetic GK rats have a different expression pattern of melatonin synthesizing enzymes. The amount of all precursors of melatonin is reduced in pineal glands of diabetic GK rats. The pineal glands of diabetic GK rats contain less noradrenaline, indicating a reduced stimulation of nighttime melatonin synthesis. The pineal glands of diabetic GK rats produce less melatonin in reaction to noradrenaline in vivo and in vitro. The pineal glands of diabetic GK rats contain less protein, probably a consequence of diabetic neuropathy. Significance This is the first time that melatonin synthesis is examined in a type 2 diabetic rat model. The present data unveiled several reasons for a reduced melatonin secretion in diabetic animals and presents an important link in the interaction between melatonin and insulin.

Phase-advance shifts of human circadian pacemaker are accelerated by daytime physical exercise.

Effects of forced sleep-wake schedules with and without physical exercise were examined on the human circadian pacemaker under dim light conditions. Subjects spent 15 days in an isolation facility separately without knowing the time of day and followed a forced sleep-wake schedule of a 23 h 40-min period for 12 cycles, and physical exercise was imposed twice per waking period for 2 h each with bicycle- or rowing-type ergometers. As a result, plasma melatonin rhythm was significantly phase advanced with physical exercise, whereas it was not changed without exercise. The difference in phase was already significant 6 days after the start of exercise. The amplitude of melatonin rhythm was not affected. A single pulse of physical exercise in the afternoon or at midnight significantly phase delayed the melatonin rhythms when compared with the prepulse phase, but the amount of phase shift was not different from that observed in the sedentary controls. These findings indicate that physical exercise accelerates phase-advance shifts of the human circadian pacemaker associated with the forced sleep-wake schedule.