Reduced Melatonin Secretion Research Articles

Alteration of circadian sleep-wake rhythm and salivary melatonin secretion in idiopathic/isolated REM sleep behavior disorder: Preliminary evidence

Objective/BackgroundIdiopathic/isolated REM sleep behavior disorder (iRBD) is widely regarded as an early sign of neurodegeneration leading to synucleinopathies. While circadian rhythm alterations in iRBD have been preliminarily demonstrated, evidence on melatonin secretion patterns in this clinical condition is limited. To address this knowledge gap, this exploratory study aimed to integrate salivary melatonin measurement with actigraphic monitoring in individuals with iRBD and age-matched healthy controls (HC) under real-life conditions. MethodsParticipants diagnosed with iRBD and HC underwent clinical evaluation and wore an actigraph for seven days and nights. Salivary melatonin concentrations were measured at five time points during the last night of recording. Comparative analyses were conducted on clinical data, actigraphic parameters, and melatonin levels between the two groups. ResultsiRBD participants (n = 18) showed greater motor (p < 0.01) and non-motor symptoms (p < 0.001), alongside disruptions in circadian sleep-wake rhythm compared to HC (n = 10). Specifically, actigraphy revealed a delayed central phase measurement (p < 0.05), reduced activity during the most active hours (p < 0.001), and decreased relative amplitude (p < 0.05). Total salivary melatonin concentration was significantly lower in iRBD (p < 0.05), with a slight but non-significant phase delay in dim light melatonin onset. ConclusionsThis exploratory study highlights a dysregulation of circadian sleep-wake rhythm coupled with reduced melatonin secretion in iRBD. Future research could add to these preliminary findings to evaluate novel treatment approaches to regulate the sleep-wake cycle and elucidate the implications of circadian dysregulation in the conversion from iRBD to neurodegeneration.

Melatonin for the regulation of sleep and other biological rhythms

Melatonin, as the hormone of the circadian system, plays a major role in regulating physiological functions and facilitating adaptation to environmental changes. Here we provide brief overview of circadian physiology, as related to the use of melatonin as hormone replacement therapy for older individuals with reduced melatonin secretion and melatonin treatment for patients with chronic insomnia or circadian desynchronization. Emphasizing the importance of minimal effective doses, we discuss the use of both immediate and delayed-release formulations, stress the significance of regular administration timing, and advise against exposure to bright light during increase in melatonin levels. Our discussion underscores that the medical guidance is essential for utilizing melatonin-containing preparations in the therapy of chronic insomnia.

Exploring Links between Pineal Gland Calcification and Central Nervous System Disease

Central nervous system disease is globally common with dysfunction of the brain and spinal cord, which significantly affects the quality of life, such as sleep disturbances. Pineal gland is pivotal in regulating sleep cycles and circadian rhythms. And melatonin, secreted by pineal gland, promotes neurodevelopment and maintains neurohomeostasis, which is also pivotal in the modulation of central nervous system disorders. In recent years, studies have found that patients with central nervous system damage often have degeneration of the pineal gland, characterized by a decrease in pineal gland volume, reduced melatonin secretion, and even parenchymal calcification. An increasing number of Alzheimer's disease patients have been observed to exhibit pineal gland calcification. Research suggests that sleep disturbances accompanying central nervous system disorders can be attributed to the degeneration of pineal gland function, indicating a potential contribution of gland calcification to central nervous system diseases. Here, we review the recent research on pineal gland calculi and discuss the potential relationship between pineal gland calcification and various central nervous system diseases, contributing to a deeper understanding of the intricate mechanisms underlying neurological disorders.

SALIVARY MELATONIN VALUES SIGNIFICANTLY CORRELATE WITH REDUCED QUALITY OF LIFE IN CHRONIC SPONTANEOUS URTICARIA PATIENTS: A PILOT STUDY.

Chronic spontaneous urticaria (CSU) is a dermatological disorder accompanied by itching that greatly affects the quality of life and quality of sleep. Therefore, it is assumed that CSU patients consequently experience reduced melatonin secretion and lower values of serum or salivary melatonin. This pilot study included 20 patients with CSU (chronic urticaria of unknown etiology that lasts for more than 6 weeks) and 10 healthy controls. All subjects were examined by a dermatovenereologist-allergist, as well as an oral pathologist, to exclude oral pathological conditions. Salivary melatonin levels were determined by ELISA and all subjects completed a standardized Dermatology Life Quality Index questionnaire and Pittsburgh Sleep Quality Index on the same day they gave a saliva sample for analysis. According to our results, 86% of CSU patients had decreased values of salivary melatonin, and lower salivary melatonin values significantly correlated with a reduced quality of life in CSU patients. This study was the first to analyze melatonin in CSU patients, also suggesting a possible new therapeutic option for the treatment of CSU.

Is Melatonin the "Next Vitamin D"?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements.

Melatonin has become a popular dietary supplement, most known as a chronobiotic, and for establishing healthy sleep. Research over the last decade into cancer, Alzheimer’s disease, multiple sclerosis, fertility, PCOS, and many other conditions, combined with the COVID-19 pandemic, has led to greater awareness of melatonin because of its ability to act as a potent antioxidant, immune-active agent, and mitochondrial regulator. There are distinct similarities between melatonin and vitamin D in the depth and breadth of their impact on health. Both act as hormones, affect multiple systems through their immune-modulating, anti-inflammatory functions, are found in the skin, and are responsive to sunlight and darkness. In fact, there may be similarities between the widespread concern about vitamin D deficiency as a “sunlight deficiency” and reduced melatonin secretion as a result of “darkness deficiency” from overexposure to artificial blue light. The trend toward greater use of melatonin supplements has resulted in concern about its safety, especially higher doses, long-term use, and application in certain populations (e.g., children). This review aims to evaluate the recent data on melatonin’s mechanisms, its clinical uses beyond sleep, safety concerns, and a thorough summary of therapeutic considerations concerning dietary supplementation, including the different formats available (animal, synthetic, and phytomelatonin), dosing, timing, contraindications, and nutrient combinations.

Modulation of aqueous humor melatonin levels by yellow-filter and its protective effect on lens.

Melatonin is mainly secreted by the pineal gland, and it is also produced by various ocular structures such as the lens. It has been recently demonstrated that melatonin ocular synthesis can be induced by blocking the blue component of white light by means of filters. Melatonin exhibits antioxidant properties that can be useful to face light-induced oxidative stress as well as oxidative events associated to ocular pathologies like cataracts. Moreover, as oxidative stress is a main event in cataract development, changes in melatonin levels could happen and be relevant in the progression of this pathology, a subject that remains uncertain. The goal of this work was to analyze the ability of a short wavelength light blocking (yellow) filter to modulate endogenous melatonin concentration and the antioxidant and cytoprotective actions induced by yellow filter's use in lens. Furthermore, we evaluated the potential changes in aqueous humor melatonin concentration from patients with cataracts. In human lens epithelial cells, white light-emitting diode (LED) light challenge reduced melatonin secretion, protein levels of the enzymes involved in melatonin synthesis (hydroxyindole-O-methyltransferase and unphosphorylated and phosphorylated forms of arylalkylamine N-acetyltransferase) and cell viability whereas increased reactive oxygen species production. Yellow filter exposure precluded melatonin secretion reduction and protected cells from oxidative damage. Consistent with cataract patient's results, significantly lower levels of melatonin were observed in aqueous humor of alloxan-induced diabetic cataract rabbits as compared to those of control rabbits. In contrast, aqueous humor melatonin levels of diabetic cataract animals maintaining in cages covered with a yellow filter resembled control values. This recovery seems to be mediated by the induction of melatonin biosynthetic enzymes protein expression. Yellow filter also preserved Nrf2 lens protein expression and superoxide dismutase protein levels and activity in diabetic animals. Modulation of endogenous ocular melatonin concentration using blocking filters might be a promising approach to prevent premature lens opacification.

Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder.

The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin’s effects in ASD and the choice of formulation type require further study. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments.

Melatonin and cortisol in individuals with spinal cord injury

Study objectivesThe aim of this study was to investigate circadian rhythm and sleep complaints in individuals with spinal cord injury (SCI) as determined by diurnal saliva melatonin and cortisol as well as activity measurements and subjective sleep quality. MethodsFourteen patients with cervical SCI (cSCI), six patients with thoracic SCI (tSCI) and eight able-bodied controls all underwent two consecutive weeks wearing a wrist actigraph in addition to filling out a sleep diary. During one 24-h period, cortisol and melatonin were measured at 4-h intervals. Furthermore, participants’ sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and their overall daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). ResultsThe cSCI group demonstrated lower melatonin levels compared with the tSCI group and the controls at the 24:00 and 04:00 time points. Moreover, at one time point the tSCI group had a higher cortisol level than the cSCI group and the controls. In addition, baseline systolic blood pressure and oxygen saturation were significantly lower in the cSCI group. No differences were found in activity measurements or self-reported sleep quality. ConclusionsIndividuals with cSCI demonstrate reduced melatonin secretion compared with tSCI individuals, but not in other circadian measures. This supports an involvement of melatonergic cervical fibers associated with the cervical lesion.

Light exposure via a head-mounted device suppresses melatonin and improves vigilant attention without affecting cortisol and comfort.

We aimed at assessing whether a head-mounted light therapy device, enriched in blue wavelengths, suppresses melatonin secretion and improves vigilant attention in the late evening hours. We also assessed whether using such light device is associated with discomfort and physiological stress. Seventeen healthy young participants (eight females) participated in a counterbalanced within-subject design during which they were exposed for 2 hr before habitual sleep time to a blue-enriched light (1500 lx) or to a lower intensity red-light (150 lx) control condition, using a new-generation light emitting diode (LED) head-mounted device. Compared to the red light control condition, blue-enriched light significantly reduced melatonin secretion and reaction times during a psychomotor vigilance task while no significant differences were detected in discomfort and cortisol levels. These results suggest that, compared to a control condition, blue-enriched light, delivered by a new-generation head-mounted device, elicits typical non-visual responses to light without detectable discomfort and physiological stress. They suggest that such devices might constitute an effective alternative to standard light boxes.

TMEM16A and TMEM16B channel proteins generate Ca2+-activated Cl− current and regulate melatonin secretion in rat pineal glands

Pinealocytes regulate circadian rhythm by synthesizing and secreting melatonin. These cells generate action potentials; however, the contribution of specific ion channels to melatonin secretion from pinealocytes remains unclear. In this study, the involvement and molecular identity of Ca2+-activated Cl- (ClCa) channels in the regulation of melatonin secretion were examined in rat pineal glands. Treatment with the ClCa channel blockers, niflumic acid or T16Ainh-A01, significantly reduced melatonin secretion in pineal glands. After pineal K+ currents were totally blocked under whole-cell patch clamp conditions, depolarization and subsequent repolarization induced a slowly activating outward current and a substantial inward tail current, respectively. Both of these current changes were dependent on intracellular Ca2+ concentration and inhibited by niflumic acid and T16Ainh-A01. Quantitative real-time PCR, Western blotting, and immunocytochemical analyses revealed that TMEM16A and TMEM16B were highly expressed in pineal glands. siRNA knockdown of TMEM16A and/or TMEM16B showed that both channels contribute to ClCa currents in pinealocytes. Conversely, co-expression of TMEM16A and TMEM16B channels or the expression of this tandem channel in HEK293 cells mimicked the electrophysiological characteristics of ClCa currents in pinealocytes. Moreover, bimolecular fluorescence complementation, FRET, and co-immunoprecipitation experiments suggested that TMEM16A and TMEM16B can form heteromeric channels, as well as homomeric channels. In conclusion, pineal ClCa channels are composed of TMEM16A and TMEM16B subunits, and these fluxes regulate melatonin secretion in pineal glands.

Effects of ghrelin on nocturnal melatonin secretion in sheep: An in vitro and in vivo approach.

Recent studies confirmed that pineal melatonin (MEL) secretion is regulated by ghrelin (GHRL) in seasonally reproductive sheep. The first in vivo experiment investigated whether the effect of GHRL on nocturnal secretion of MEL in sheep is mediated by type 2 serotonin receptors. Sheep ( = 16) were intravenously injected with GHRL (2.5 μg/kg of BW) and meta-Chlorophenylpiperazine (mCPP; a mixed agonist of 5-HT2B/5-HT2C receptors; 1 mg/kg BW), either combined or individually, during the short-day (SDS) and long-day (LDS) seasons. Blood samples were collected at 15-min intervals for 4 h. The second in vitro experiment examined the effect of GHRL (10 ng/mL) on MEL secretion by pineal gland (PG) explants incubated for 5 h. The expression levels and/or concentrations of tryptophan 5-hydroxylase 1 (TPH1), aralkylamine N-acetyltransferase (AA-NAT), and the phosphorylated form of AA-NAT (p31T-AA-NAT) were determined at selected time points during the SDS and LDS seasons. The experiments demonstrated that GHRL reduced MEL secretion ( < 0.01) during the SDS season. Administration of mCPP or a combination of GHRL + mCPP stimulated MEL secretion ( < 0.01) regardless of the season. Furthermore, GHRL regulated nightly MEL secretion in a TPH1-independent manner. However, during the SDS season, GHRL reduced p31T-AA-NAT expression and the AA-NAT concentration ( < 0.01) and inhibited MEL secretion ( < 0.001), whereas during the LDS season, GHRL had no effect on MEL secretion or on the expression of the examined enzymes. These findings indicate that GHRL directly and indirectly affects PG activity in sheep and that the photoperiod modulates the effects of GHRL.

Modulation of Ca2+ oscillation and melatonin secretion by BKCa channel activity in rat pinealocytes.

The pineal glands regulate circadian rhythm through the synthesis and secretion of melatonin. The stimulation of nicotinic acetylcholine receptor due to parasympathetic nerve activity causes an increase in intracellular Ca(2+) concentration and eventually downregulates melatonin production. Our previous report shows that rat pinealocytes have spontaneous and nicotine-induced Ca(2+) oscillations that are evoked by membrane depolarization followed by Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCCs). These Ca(2+) oscillations are supposed to contribute to the inhibitory mechanism of melatonin secretion. Here we examined the involvement of large-conductance Ca(2+)-activated K(+) (BKCa) channel conductance on the regulation of Ca(2+) oscillation and melatonin production in rat pinealocytes. Spontaneous Ca(2+) oscillations were markedly enhanced by BKCa channel blockers (1 μM paxilline or 100 nM iberiotoxin). Nicotine (100 μM)-induced Ca(2+) oscillations were also augmented by paxilline. In contrast, spontaneous Ca(2+) oscillations were abolished by BKCa channel opener [3 μM 12,14-dichlorodehydroabietic acid (diCl-DHAA)]. Under whole cell voltage-clamp configurations, depolarization-elicited outward currents were significantly activated by diCl-DHAA and blocked by paxilline. Expression analyses revealed that the α and β3 subunits of BKCa channel were highly expressed in rat pinealocytes. Importantly, the activity of BKCa channels modulated melatonin secretion from whole pineal gland of the rat. Taken together, BKCa channel activation attenuates these Ca(2+) oscillations due to depolarization-synchronized Ca(2+) influx through VDCCs and results in a recovery of reduced melatonin secretion during parasympathetic nerve activity. BKCa channels may play a physiological role for melatonin production via a negative-feedback mechanism.

Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness

In the past 50 y, there has been a decline in average sleep duration and quality, with adverse consequences on general health. A representative survey of 1,508 American adults recently revealed that 90% of Americans used some type of electronics at least a few nights per week within 1 h before bedtime. Mounting evidence from countries around the world shows the negative impact of such technology use on sleep. This negative impact on sleep may be due to the short-wavelength-enriched light emitted by these electronic devices, given that artificial-light exposure has been shown experimentally to produce alerting effects, suppress melatonin, and phase-shift the biological clock. A few reports have shown that these devices suppress melatonin levels, but little is known about the effects on circadian phase or the following sleep episode, exposing a substantial gap in our knowledge of how this increasingly popular technology affects sleep. Here we compare the biological effects of reading an electronic book on a light-emitting device (LE-eBook) with reading a printed book in the hours before bedtime. Participants reading an LE-eBook took longer to fall asleep and had reduced evening sleepiness, reduced melatonin secretion, later timing of their circadian clock, and reduced next-morning alertness than when reading a printed book. These results demonstrate that evening exposure to an LE-eBook phase-delays the circadian clock, acutely suppresses melatonin, and has important implications for understanding the impact of such technologies on sleep, performance, health, and safety.

Adrenoceptor Expression and Diurnal Rhythms of Melatonin and Its Precursors in the Pineal Gland of Type 2 Diabetic Goto-Kakizaki Rats

A decrease in the nighttime release of the pineal hormone melatonin is associated with aging and chronic diseases in animals an humans. Melatonin has a protective role in type 2 diabetes; however, its synthesis itself is affected in the disease. The aim of this study was to detect crucially impaired steps in the pineal melatonin synthesis of type 2 diabetic Goto-Kakizaki (GK) rats. Therefore, plasma melatonin concentrations and the pineal content of melatonin and its precursors (tryptophan, 5-hydroxytryptophan, serotonin, and N-acetylserotonin) were quantified in GK rats compared with Wistar rats (each group 8 and 50 wk old) in a diurnal manner (four animals per group and per time point). Additionally, the expression of pineal adrenoceptor subtype mRNA was investigated. We found that in diabetic GK rats, 1) inhibitory alpha-2-adrenoceptors are significantly more strongly expressed than in Wistar rats, 2) the formation of 5-hydroxytryptophan is crucially impaired, and 3) the pineal gland protein content is significantly reduced compared with that in Wistar rats. This is the first time that melatonin synthesis is examined in a type 2 diabetic rat model in a diurnal manner. The present data unveil several reasons for a reduced melatonin secretion in diabetic animals and present an important link in the interaction between melatonin and insulin.

Pharmacokinetics of orally administered melatonin in critically ill patients

Critically ill patients exhibit reduced melatonin secretion, both in nocturnal peaks and basal daytime levels. Oral melatonin supplementation may be useful for known sedative and antioxidant properties.

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.

Short-wavelength sensitive nonvisual photoreceptors, their role in the pathological effects of night illumination

Event Abstract Back to Event Short-wavelength sensitive nonvisual photoreceptors, their role in the pathological effects of night illumination Bela Vigh1*, Maria J. Silva2, Vincze Csilla1, Attila Magyar1, Laszlo Szabo1 and Szel Agoston1 1 Department of Human Morphology and Developmental Biology, Semmelweis University, Hungary 2 Occupational Health Service, Centro Hospitalar de Lisboa Ocidental, Hospital Egas Moniz, Portugal Night-illumination disturbs normal diurnal periodicity thereby increases health risks e.g. gastro-intestinal or cardiovascular disorders, overweight, depression, disturbed sexual activity, brest cancer and colorectal cancer. Normal diurnal periodicity is driven by a genetical self-regulating clock-system present in several organs and having approximately 24 hour-long periods. This clock-system is synchronized by the suprachiasmatic nucleus and adapted to circadian and circannual light periods of the actual environment by nonvisual retinal, pineal and deep brain photoreceptors. The hormone melatonin produced by the pineal organ at night plays a fundamental role in the circadian and circannual periodic synchronization of biologic functions. Short wavelenght light was found to result a melatonin suppression and is an important factor producing pathological events caused by night illumination. In the present work we immunocytochemically localized blue-light sensitive molecules in nonvisual photo-receptors of various experimental animals. Cryptochrome-1, 2, pinopsin and OS-2 being short-wavelength-sensitive molecules were localized in retinal, pineal and deep encephalic photoreceptors. In the retina cryptochrome-2 was localized in nuclei of some photoreceptors, in the inner and outer granular layer, while cryptochrome-1 was found in the cytoplasm of a population of photoreceptors. Pinopsin and OS-2 were localized in the outer segment of some cone-like photoreceptors. The pineal organ representing the main nonvisual photoreceptor in submammalians has a retina-like structure. In the pineal photoreceptors – among other photoreceptor molecules – cryptochrome-2, pinopsin and OS-2 were found. Cryptochrome-2 and Pinopsin was also demonstrated in the suprachiasmatic nucleus being the main circadian pacemaker of the body and in the deep encephalic photoreceptors of lower vertebrates. Our immunocytochemical studies localize and confirm the presence of pinopsin, cryptochromes and OS-2 being blue light sensitive molecules in all nonvisual photoreceptor areas. These results strengthen the view that blue light-free-illumination or vearing blue-light-filtering glasses may reduce health risks caused by reduced melatonin secretion during night-illumination. As also high-intensity red light supresses melatonin secretion, filtered light at night should be of low intensity. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Behavioural neuroscience Citation: Vigh B, Silva MJ, Csilla V, Magyar A, Szabo L and Agoston S (2009). Short-wavelength sensitive nonvisual photoreceptors, their role in the pathological effects of night illumination. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.131 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Mar 2009; Published Online: 04 Mar 2009. * Correspondence: Bela Vigh, Department of Human Morphology and Developmental Biology, Semmelweis University, Semmelweis, Hungary, vigh@ana2.sote.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Bela Vigh Maria J Silva Vincze Csilla Attila Magyar Laszlo Szabo Szel Agoston Google Bela Vigh Maria J Silva Vincze Csilla Attila Magyar Laszlo Szabo Szel Agoston Google Scholar Bela Vigh Maria J Silva Vincze Csilla Attila Magyar Laszlo Szabo Szel Agoston PubMed Bela Vigh Maria J Silva Vincze Csilla Attila Magyar Laszlo Szabo Szel Agoston Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Circadian rhythms, sleep, and the menstrual cycle

Women with ovulatory menstrual cycles have a circadian rhythm superimposed on the menstrual-associated rhythm; in turn, menstrual events affect the circadian rhythm. In this paper, we review circadian rhythms in temperature, selected hormone profiles, and sleep–wake behavior in healthy women at different phases of the menstrual cycle. The effects on menstrual cycle rhythmicity of disrupted circadian rhythms, for example, with shiftwork and altered circadian rhythms in women with menstrual-related mood disturbances, are discussed. Compared to the follicular phase, in the post-ovulation luteal phase, body temperature is elevated, but the amplitude of the temperature rhythm is reduced. Evidence indicates that the amplitude of other rhythms, such as melatonin and cortisol, may also be blunted in the luteal phase. Subjective sleep quality is lowest around menses, but the timing and composition of sleep remains relatively stable across the menstrual cycle in healthy women, apart from an increase in spindle frequency activity and a minor decrease in rapid eye movement (REM) sleep during the luteal phase. Disruption of circadian rhythms is associated with disturbances in menstrual function. Female shiftworkers compared to non-shiftworkers are more likely to report menstrual irregularity and longer menstrual cycles. There also is accumulating evidence that circadian disruption increases the risk of breast cancer in women, possibly due to altered light exposure and reduced melatonin secretion. Further investigations into the biological consequences of circadian disruption in women will offer insight into some menstrual-associated disorders, including mood changes, as well as reproductive function and possible links with breast cancer.

Agonistes et antagonistes des récepteurs mélatoninergiques : perspectives thérapeutiques

The chronobiotic neurohormone melatonin, synthetized in the pineal gland during darkness periods governs the circadian and seasonal biological rhythms. Physiologically, melatonin regulates the sleep/activity alternance, together with the circadian cycle of body temperature and cortisol secretion, and influences various immune, endocrine and metabolic functions. Dysfunction of the endogenous melatonin secretion is associated with mood and behavioral disorders including body weight. Patients with severe depression exhibit desynchronized and reduced melatonin secretion, in parallel with marked sleep disturbances whereas exogenous melatonin administration and antidepressive drugs restore melatonin secretion. A dysregulated melatonin secretion is also observed in obese subjects. Implication of melatonin in these disorders stimulated the search for melatonin analogues with enhanced antidepressive and body weight control effects. The melatoninergic agonist S 20098, or agomelatin, disclosed a potent antidepressive and anxiolytic activity in preclinical studies, which was confirmed in clinical trials in patients with major depression. The antagonist S 20928 was shown to limit seasonal weight gain in an hibernating rodent model. Thus, development of melatoninergic agonists and antagonists appear as an innovative approach in the treatment of depression and obesity, two major public health problems.

Diazepam increases melatonin secretion of photosensitive pineal organs of trout in the photopic and mesopic range of illumination

The pineal organ of teleost fish receives photic information directly through specialized photoreceptor cells that transmit their light response to second-order neurons and respond also with an endocrine light-dependent melatonin signal. In the present study we have analyzed the action of diazepam, a full agonist of the benzodiazepine receptor, on the photic regulation of the endocrine melatonin response of cultured trout pineal organs. Melatonin release of explanted pineal organs was clearly dependent on the irradiance of incident light with a maximum change during mesopic illuminations. Addition of diazepam to the superfusion medium significantly increased melatonin production in the mesopic and partly in the photopic range of illumination, without showing clear effects in the dark-adapted organ. Flumazenil, a central acting benzodiazepine antagonist, slightly reduced melatonin secretion. The action of diazepam appears to be comparable to a dark-pulse in the mesopic range of illuminations.