Pattern Of 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.

Circadian rhythm regulation in the sea cucumber Apostichopus japonicus: Insights into clock gene expression, photoperiod susceptibility, and neurohormone signaling

Sea cucumber Apostichopus japonicus displays the typical circadian rhythms. This present study investigated the molecular regulation of clock genes, as well as monoamines and melatonin, in multiple tissues of A. japonicus, responding to the photoperiod. In order to determine their pivotal role in circadian rhythms, the crucial clock genes, namely AjClock, AjArnt1, AjCry1, and AjTimeless, were identified and a comprehensive analysis of their expressions across various tissues in adult A. japonicus was conducted, revealing the potential existence of central and peripheral oscillators. Results demonstrated that the tissues of polian vesicle and nerve ring exhibited significant clock gene expression associated with the orchestration of circadian regulation, and that environmental light fluctuations exerted influence on the expression of these clock genes. However, a number of genes, such as AjArnt1 and AjCry1, maintained their circadian rhythmicity even under continuous light conditions. Moreover, we further investigated the circadian patterns of melatonin (MT), serotonin (5-HT), and dopamine (DA) secretion in A. japonicus, data that underscored the tissue-specific regulatory differences and the inherent adaptability to dynamic light environments. Collectively, these findings will provide the molecular mechanisms controlling the circadian rhythm in echinoderms and the candidate tissues playing the role of central oscillators in sea cucumbers.

Melatonin secretion patterns are associated with cognitive vulnerability and brain structure in bipolar depression

ABSTRACT Circadian rhythm disruption is a core symptom of bipolar disorder (BD), also reflected in altered patterns of melatonin release. Reductions of grey matter (GM) volumes are well documented in BD. We hypothesized that levels and timing of melatonin secretion in bipolar depression could be associated with depressive psychopathology and brain GM integrity. The onset of melatonin secretion under dim light conditions (DLMO) and the amount of time between DLMO and midsleep (i.e. phase angle difference; PAD) were used as circadian rhythm markers. To study the time course of melatonin secretion, an exponential curve fitting the melatonin values was calculated, and the slope coefficients (SLP) were obtained for each participant. Significant differences were found between HC and BD in PAD measures and melatonin profiles. Correlations between PAD and depressive psychopathology were identified. Melatonin secretion patterns were found to be associated with GM volumes in the Striatum and Supramarginal Gyrus in BD. Our findings emphasized the role of melatonin secretion role as a biological marker of circadian synchronization in bipolar depression and provided a novel insight for a link between melatonin release and brain structure.

Dim light melatonin patterns in unaffected offspring of parents with bipolar disorder: A case-control high-risk study

BackgroundCircadian dysregulation has long been thought to be a key component in the pathophysiology of bipolar disorder (BD). However, it remains unclear whether this dysregulation constitutes a risk factor, manifestation, or consequence of BD. This study aimed to compare dim light melatonin secretion patterns between unaffected offspring of parents with BD (OBD) and offspring of control parents (OCP). MethodsThis case-control study included unaffected OBD (mean age 14.0 years; male 50.0 %) and age- and sex-matched OCP (mean age 13.0 years; male: 43.5 %). Seventeen saliva samples were collected in dim light conditions. Dim light melatonin onset (DLMO), phase angles, and area under the curve (AUC) were calculated. Results185 saliva samples from 12 OBD (n = 12) and 741 from OCP (n = 46) were collected. Unaffected OBD had a significant lower nocturnal melatonin level (14.8 ± 4.6 vs. 20.3 ± 11.7 pg/mL) and a smaller melatonin AUC within two hours after DLMO (35.5 ± 11.3 vs. 44.6 ± 18.1 pg/mL) but a significant larger phase angle between DLMO and sleep onset (2.2 ± 1.0 vs. 1.4 ± 1.2 h) than OCP. There was no significant between-group difference in DLMO. The graphic illustrations showed a considerably flattened melatonin secretion in unaffected OBD. LimitationsThe main limitations include lack of 24-h dim melatonin secretion measurement, large age range of participants, and small sample size. ConclusionsThese findings suggest that unaffected OBD already presented with circadian rhythm dysregulations. Future investigations are needed to clarify the role of abnormal melatonin secretion in the onset of BD.

Hypophysial angiogenesis decodes annual time and underlies physiological adaptation to seasonal changes in the environment.

Adaptation to annual changes in the environment is controlled by hypophysial hormones. In temperate zones, photoperiod is the primary external cue that regulates annual biological cycles and is translated by the pattern of melatonin secretion acting primarily in the hypophysial pars tuberalis. Angiogenic mechanisms within this tissue contribute to decode the melatonin signal through alternative splicing of the vascular endothelial growth factor A (VEGF-A) gene in both the pars tuberalis and the capillary loops of the infundibulum. The resulting melatonin-evoked differential productions of VEGF-A isoforms will induce seasonal remodeling of the vascular connection between the hypothalamus and hypophysis, and act as paracrine messengers in the pars distalis to generate the required seasonal endocrine response. Specifically, the long melatonin signal in winter upregulates antiangiogenic VEGF-A isoforms, which will reduce the number of vascular loops and the density of VEGF receptors in endocrine and folliculo-stellate (FS) cells, inhibit prolactin secretion, and stimulate FSH. In contrast, the short melatonin signal in summer upregulates proangiogenic VEGF-A isoforms that will increase the number of vascular loops and the density of VEGF receptors in endocrine and FS cells, stimulate prolactin secretion, and suppress FSH. A similar system has been identified in long day seasonal breeders, revealing that this is a conserved mechanism of adaptation across species. Thus, an angiogenesis-based, intrahypophysial system for annual time measurement controls local microvascular plasticity and conveys the photoperiodic signal readout from the melatonin sensitive pars tuberalis to the endocrine cells of the pars distalis to regulate seasonal adaptation to the environment.

Melatonin Rhythm and Its Relation to Sleep and Circadian Parameters in Children and Adolescents With Autism Spectrum Disorder.

IntroductionSleep problems are prevalent among individuals with autism spectrum disorder (ASD), and a role has been attributed to melatonin in this multifactorial comorbidity.MethodsA cross-sectional study was conducted on 41 autistic children and adolescents (9.9 ± 3.02) and 24 children and adolescents with a normal intellectual function (8.42 ± 2.43) were used as controls. Subjects were matched for sex, body mass index, and pubertal stage, and all were drug-naive. Circadian and sleep parameters were studied using an ambulatory circadian monitoring (ACM) device, and saliva samples were collected around the onset of sleep to determine dim light melatonin onset (DLMO).ResultsPrepubertal individuals with ASD presented later DLMO and an earlier decline in melatonin during adolescence. A relationship was found between melatonin and both sleep and circadian parameters. Participants and controls with later DLMOs were more likely to have delayed sleep onset times. In the ASD group, subjects with the later daytime midpoint of temperature had a later DLMO. Later melatonin peak time and DLMO time were related to lower general motor activity and lower stability of its rhythms.ConclusionThe melatonin secretion pattern was different in individuals with ASD, and it showed a relationship with sleep and circadian parameters. Alterations in DLMO have not been previously reported in ASD with the exception of more variable DLMO timing; however, high variability in the study design and sample characteristics prevents direct comparison. The ACM device enabled the measurement of circadian rhythm, a scarcely described parameter in autistic children. When studied in combination with other measures such as melatonin, ACM can offer further knowledge on sleep problems in ASD.

Investigating the relationship between melatonin patterns and methylation in circadian genes among day shift and night shift workers

ObjectivesMechanisms underlying the carcinogenicity of night shift work remain uncertain. One compelling yet understudied cancer mechanism may involve altered DNA methylation in circadian genes due to melatonin secretion patterns. The...

Membrane Melatonin Receptors Activated Cell Signaling in Physiology and Disease.

The pineal hormone melatonin has attracted great scientific interest since its discovery in 1958. Despite the enormous number of basic and clinical studies the exact role of melatonin in respect to human physiology remains elusive. In humans, two high-affinity receptors for melatonin, MT1 and MT2, belonging to the family of G protein-coupled receptors (GPCRs) have been cloned and identified. The two receptor types activate Gi proteins and MT2 couples additionally to Gq proteins to modulate intracellular events. The individual effects of MT1 and MT2 receptor activation in a variety of cells are complemented by their ability to form homo- and heterodimers, the functional relevance of which is yet to be confirmed. Recently, several melatonin receptor genetic polymorphisms were discovered and implicated in pathology—for instance in type 2 diabetes, autoimmune disease, and cancer. The circadian patterns of melatonin secretion, its pleiotropic effects depending on cell type and condition, and the already demonstrated cross-talks of melatonin receptors with other signal transduction pathways further contribute to the perplexity of research on the role of the pineal hormone in humans. In this review we try to summarize the current knowledge on the membrane melatonin receptor activated cell signaling in physiology and pathology and their relevance to certain disease conditions including cancer.

Testis development in the Japanese eel is affected by photic signals through melatonin secretion.

ObjectiveAccording to reported spawning characteristics of Japanese eel, Anguilla japonica, which exhibit spawning and migration patterns that are synchronized with lunar cycles and photoperiod, we hypothesized that a close association exists between specific photic signals (daylight, daylength, and moonlight) and endocrinological regulation. Given the photic control in melatonin secretion, this hypothesis was tested by investigating whether melatonin signals act as mediators relaying photic signals during testis development in the eel.MethodsWe examined changes in melatonin-secretion patterns using time-resolved fluorescence immunoassays in sexually immature and mature male Japanese eels under the condition of a new moon (NM) and a full moon (FM).ResultsThe eye and plasma melatonin levels exhibited a nocturnal pattern under a 12-h light: dark cycle (12L12D) or under constant darkness (DD), but not with constant light (LL). Eye melatonin levels were similar under the 12L12D and short-day (9L15D) conditions. In the long-day condition (15L9D), secreted plasma melatonin levels were stable, whereas short-day melatonin secretion began when darkness commenced. Sexual maturation began at 8 weeks following intraperitoneal injection of human chorionic gonadotropin (hCG), and NM exposure led to significantly higher eye and plasma melatonin levels compared with those detected under FM exposure.

Melatonin secretion in migraine patients: the current state of knowledge.

Zduńska et al. [1] present the results of a pilot study exploring changes in melatonin serum concentration in migraine patients, and the clinical implications of these changes. Melatonin secretion may be altered for several reasons, and migraine is one of those clinical conditions where melatonin secretion can be changed. Correlations between migraine clinical phenotype and melatonin secretion pat-terns may bring exciting results. Alterations in melatonin secretion in migraine has not been explained. Studies which aim at exploring the mechanism(s) of action of melatonin secretion in migraine patients may provide an insight into the pathogenesis of migraine and contribute to effective treatment options.

Effects of daytime exposure to different monochromatic lights on the excretion of 6-sulfatoxymelatonin (aMT6s) in a hospital environment

ABSTRACT Hospitalized patients are frequently deprived of contact with natural light and constantly exposed to artificial lighting, losing biological synchronism. However, few studies have been conducted to assess the consequences of inadequate exposure to light in hospital environments, whether related to insufficient light in the period daytime, or to light peaks at night. This study assesses the effect of daytime exposure to different monochromatic lights on the excretion of 6-sulfatoxymelatonin (aMT6s), a hormone that reflects variations in the light/dark cycle. The light intensity was adjusted to 300 lx. Forty voluntary patients under transfusion were randomly assigned into five groups of light exposure for five hours, during the day. The concentration of aMT6s was determined in the urine samples collected at four intervals in a period of 24 hours during two days (before and at intervention). Exposure to green light resulted in significant acute melatonin reduction; blue light, in delay of night secretion; red, yellow and white light, kept it unaltered. These findings indicate that exposure to light during the day can lead to changes in the pattern of melatonin secretion. This research can be useful in artificial lighting environments, such as hospitals, to maintain adequate lighting and preserve the sleep/wake cycle.

Seasonal effects on fertility in gilts and sows

The ancestral wild pig is a short day length seasonal breeder. The domestic pig appears to have retained some of this seasonality as evidenced by a reduction in fertility during the summer—autumn period. The most important aspect of this seasonality is a reduction in the number of mated sows that farrow. Many of these sows conceive and embryos develop normally for 20 - 25 days before pregnancy is terminated and the sow returns to oestrus (25 - 35 days after mating). In other species, transduction of photoperiodic information is achieved by release of melatonin during the dark period. In the pig, the pattern of melatonin secretion and the subsequent hypothalamo—pituitary—gonadal responses appear to be more complex. A relatively high light intensity is required for pigs to generate a distinct diurnal melatonin rhythm and they appear unable to respond appropriately to abrupt changes in photoperiod. Pigs on restricted feeding and maintained under long photoperiods (but not under short photoperiods) have higher concentrations of melatonin than do similarly maintained pigs fed ad libitum. Continuous release melatonin implants have a deleterious effect on farrowing rate, suggesting that the abnormally high melatonin concentrations observed in sows in summer—autumn play a role in the pathogenesis of seasonal infertility. Ad libitum feeding of sows during the first few weeks of pregnancy may prevent the increase in melatonin concentrations and so remove the seasonal influence on fertility. The pituitary response to different photoperiods is also somewhat confusing. Although there is some evidence of increased sensitivity to the negative feedback of ovarian steroids in the prepubertal gilts and weaned sows during summer—autumn, LH concentrations are increased in early pregnant sows. It is proposed that the failure of sows to maintain pregnancy in summer—autumn results from disruption of maternal recognition of pregnancy causing regression of the corpora lutea, loss of pregnancy and return of the sow to oestrus.

1004 Smith-&amp;lt;Magenis Syndrome (SMS) Circadian Abnormalities And Biological Rhythms

Abstract Introduction SMS is a rare neurodevelopmental disorder that manifests with craniofacial abnormalities, behavioral disturbances, and a severe sleep disorder. It has been reported that many SMS patients have an inverted melatonin secretion pattern (peaking during the daytime) although a small minority have near normal patterns. The goal of this study was to better characterize the intra- and inter-patient variability of melatonin secretion patterns and investigate a potential relationship with sleep behavior in SMS patients. Methods In this observational study, sleep behaviors of patients (N=8, 1 female, ages: 7 - 35) with SMS were characterized through caretaker surveys. On 3 separate occasions, patients had hourly serum melatonin levels sampled for 36 hours. From these data, peak serum melatonin concentration and time of peak concentration were determined. Inter- and intra-patient variability was characterized by zero lag correlation of the melatonin concentration timeseries across and within patients, respectively. The relationship between peak melatonin concentration, peak time, and sleep latency was analyzed by a generalized linear model, GLM. Results Peak melatonin concentrations varied across SMS patients with a range of 3.55pg/ml - 49.65pg/ml (mean 14.18 ± 15.19pg/ml). Time of peak melatonin concentrations ranged from 0400h-2100h (mean 1422 ± 6h). Correlation coefficients characterizing intra-patient variability ranged from -0.0098 to 0.89 (mean 0.55 ± 0.2533). Correlation coefficients characterizing inter-patient variability ranged from -0.75 to 0.79 (mean of 0.18 ± 0.52). Sleep latency ranged from 8.4min - 36.35min (mean of 21.99 ± 9.77 min). GLM analysis demonstrated a significant, positive effect of peak time with sleep latency (p=0.022). Conclusion Consistent with previous findings, our study confirms that SMS patients have abnormal circadian rhythms. Our work extends this body of literature by demonstrating a significant degree of inter-patient variability with relatively stable intra-patient variability. Preliminary evidence suggests that the timing of melatonin peak may be related to sleep onset latency. Support This work was supported by Vanda Pharmaceuticals Inc.

Reproductive management of the transitional mare

The mare is a seasonally polyoestrous long-day breeder with a physiological breeding season lasting from April–October in the Northern Hemisphere. The hypothalamic-pituitary-gonadal axis in the mare is subject to a circannual endogenous rhythm that is primarily regulated by day length. Increasing ambient photoperiod in the spring alters the pattern of melatonin secretion. The resulting stimulation of hypothalamic gonadotropin-releasing hormone secretion triggers pituitary follicular stimulating hormone release and follicular growth. Exposure of mares in deep anoestrus to a stimulatory photoperiod remains the most successful method of advancing the first ovulation of the season. The most commonly used lighting regimen is providing a fixed length of 15–16 hours of light exposure and 8–9 hours of dark, with a minimum light intensity in a stable of 100-lux (100–200 watt incandescent bulb). Other methods include using an additional 2.5 hours of light beginning at sunset and a pulse lighting system, providing 1 hour of light, 9.5–10.5 hours after the onset of darkness, during the photosensitive phase. Alternatively, the EquilumeTMlight masks provide a unilateral LED light source emitting 50 lux of blue-light directly to the eye during the hours after dusk (until 11 pm). Mares that have not been maintained under lights, or that have been exposed to ineffective light therapy, may require therapeutic hormonal intervention to advance the onset of the first ovulation of the season. Many hormone protocols involving progestins, GnRH, dopamine agonists and recombinant luteinising hormone/follicle stimulating hormone have been studied with variable results. Therapy is typically more effective when started either in late transitional mares or following a period of stimulatory artificial photoperiod.

Reproductive management of the transitional mare

The mare is a seasonally polyoestrous long-day breeder with a physiological breeding season lasting from April–October in the Northern Hemisphere. The hypothalamic-pituitary-gonadal axis in the mare is subject to a circannual endogenous rhythm that is primarily regulated by day length. Increasing ambient photoperiod in the spring alters the pattern of melatonin secretion. The resulting stimulation of hypothalamic gonadotropin-releasing hormone secretion triggers pituitary follicular stimulating hormone release and follicular growth. Exposure of mares in deep anoestrus to a stimulatory photoperiod remains the most successful method of advancing the first ovulation of the season. The most commonly used lighting regimen is providing a fixed length of 15–16 hours of light exposure and 8–9 hours of dark, with a minimum light intensity in a stable of 100-lux (100–200 watt incandescent bulb). Other methods include using an additional 2.5 hours of light beginning at sunset and a pulse lighting system, providing 1 hour of light, 9.5–10.5 hours after the onset of darkness, during the photosensitive phase. Alternatively, the EquilumeTM light masks provide a unilateral LED light source emitting 50 lux of blue-light directly to the eye during the hours after dusk (until 11 pm). Mares that have not been maintained under lights, or that have been exposed to ineffective light therapy, may require therapeutic hormonal intervention to advance the onset of the first ovulation of the season. Many hormone protocols involving progestins, GnRH, dopamine agonists and recombinant luteinising hormone/follicle stimulating hormone have been studied with variable results. Therapy is typically more effective when started either in late transitional mares or following a period of stimulatory artificial photoperiod.

Association between melatonin secretion patterns and living situations in children

Association between melatonin secretion patterns and living situations in children

Relationship between classroom seat location and the sleep situation, melatonin secretion patterns of school children

Relationship between classroom seat location and the sleep situation, melatonin secretion patterns of school children

Red light at night permits the nocturnal rise of melatonin production in horses

Exposure to white light at night suppresses melatonin production, impacts circadian rhythms and contributes to ill-health in humans. Human interaction with horses frequently occurs at night. We tested the hypothesis that dim red light would not suppress the nightly rise in serum melatonin levels in horses. In a crossover design, six horses were maintained for consecutive 48h periods under a Light: Red (LR) and a Light: Dark (LD) photo-schedule. Transitions from light (>200lux, polychromatic white light) to red (5lux, peak wavelength 625nm) or dark (<0.5lux), and vice versa, coincided with ambient sunset and sunrise times. Blood was collected at 2h intervals for 24h during each treatment via indwelling jugular catheters. Samples were harvested for serum and stored at −20°C until assayed for melatonin by radioimmunoassay. Repeated measures two-way ANOVA and t-tests analysed for differences in LR and LD melatonin profiles and their circadian rhythm parameters.No time×treatment interaction or effect of treatment on serum melatonin levels were demonstrated (P>0.05). A robust main effect of time (P<0.0001) predominated, with melatonin levels rising at night under both treatments. Statistically significant differences were not observed when LR and LD were compared for circadian rhythm measures of night time peak, area under the curve (AUC), or for times of onset (evening rise), offset (morning decline), or peak duration. Low intensity red light at night did not impact the pattern of melatonin secretion in this study and is, therefore, unlikely to impact the physiology of circadian or seasonal regulation.

Evening melatonin timing secretion in real life conditions in patients with Alzheimer disease of mild to moderate severity

BackgroundCircadian dysfunction is thought to take part in the pathogenesis of sleep disorders in Alzheimer's disease (AD) and in AD pathophysiology itself. ObjectiveOur study aims to calculate dim light melatonin onset (DLMO) secretion in order to define the circadian phase in patients with AD at an early stage of the disease. MethodsTwenty-one patients (M/F: 11/10; mean age 74.1 ± 5.4 years; mean disease duration 3.4 ± 1.6 years) with a diagnosis of AD and 17 healthy controls (HC; M/F: 10/7; mean age 67.47 ± 3.8 years) were investigated for subjective nocturnal sleep quality and chronotype, for DLMO and quantitative aspects of the evening melatonin secretion by means of a 5-point in-home evening melatonin saliva test. ResultsSubjective sleep quality score on the Pittsburgh Sleep Quality Index questionnaire (PSQI) above 5 (p = 0.24), insomnia frequency as measured by Sleep Condition Indicator Questionnaire (p = 0.823) and the subjective chronotype according to Morning Evening Questionnaire (MEQ) scores distribution (p = 0.464) did not differ between AD and HC. However, DLMO occurred significantly later (55 min; p = 0.028), and melatonin secretion following DLMO was significantly decreased in AD patients compared to HC. ConclusionInitial evening secretion of melatonin proves to be delayed and mildly impaired in patients with a mild/moderate form of Alzheimer disease while patients' subjective sleep parameters and chronotype are reported to be similar to those of HC. These results indicate that subclinical altered patterns of melatonin secretion occur in subjects with AD at an early stage of the disease.

Effects of change in residence to a mountain village on children’s melatonin responses

ABSTRACT Sleep problems are especially serious in Japan. The purpose of the present study was to clarify the effects of a shift of residence to a mountain village on children’s melatonin responses. The participants were 19 children (nine males and ten females, 10–15 years old) who participated in the Mountain Village Educational Program. After excluding a girl with confirmed deficits, the data of 18 participants were used for analysis. We measured salivary melatonin concentration and assessed the self-completed questionnaire survey on sleep situation. Although the proportion of people who showed a greater salivary melatonin concentration at night than in the morning immediately after starting the Mountain Village Educational Program was 50%, after that it was shown that melatonin concentration increased at night and decreased in the morning. The results demonstrated that all participants showed a salivary melatonin secretion pattern of night > morning after approximately 3.5 months. Based on these findings, the Mountain Village Educational Program, which involves a shift of residence to a mountain village, has the potential to improve children’s sleep. Abbreviations: DLMO: Dim light melatonin onset; MVEP: Mountain Village Educational Program