Melatonin Rhythm Research Articles

Maternal circadian rhythm and its implications for offspring health

This review presents data on the circadian system hierarchy and its unique reorganization at the onset of pregnancy, which plays a fundamental role in maintaining maternal homeostasis and creating optimal conditions for the implementation of the genetic program of fetal development. A particular emphasis is made on the protective mechanisms of the circadian rhythm of maternal melatonin, which is the primary messenger of biorhythms. This paper thoroughly discusses the mechanisms and consequences of maternal chronodisruption in pregnant women exposed to adverse environmental conditions (shift work, stress, irregular nutrition, etc.), as well as in those with chronodestruction-related diseases (obesity, diabetes mellitus, etc.). Elucidating the circadian system status in the patients and, in particular, whether they have a daily rhythm of melatonin production will determine a new approach to risk assessment and timely prevention of cardiovascular, metabolic, neuroendocrine and mental disorders in the offspring in later life.

Physiological consequences of space flight, including abnormal bone metabolism, space radiation injury, and circadian clock dysregulation: Implications of melatonin use and regulation as a countermeasure.

Exposure to the space environment induces a number of pathophysiological outcomes in astronauts, including bone demineralization, sleep disorders, circadian clock dysregulation, cardiovascular and metabolic dysfunction, and reduced immune system function. A recent report describing experiments aboard the Space Shuttle mission, STS-132, showed that the level of melatonin, a hormone that provides the biochemical signal of darkness, was decreased during microgravity in an in vitro culture model. Additionally, abnormal lighting conditions in outer space, such as low light intensity in orbital spacecraft and the altered 24-hlight-dark cycles, may result in the dysregulation of melatonin rhythms and the misalignment of the circadian clock from sleep and work schedules in astronauts. Studies on Earth have demonstrated that melatonin regulates various physiological functions including bone metabolism. These data suggest that the abnormal regulation of melatonin in outer space may contribute to pathophysiological conditions of astronauts. In addition, experiments with high-linear energy transfer radiation, a ground-based model of space radiation, showed that melatonin may serve as a protectant against space radiation. Gene expression profiling using an in vitro culture model exposed to space flight during the STS-132 mission, showed that space radiation alters the expression of DNA repair and oxidative stress response genes, indicating that melatonin counteracts the expression of these genes responsive to space radiation to promote cell survival. These findings implicate the use of exogenous melatonin and the regulation of endogenous melatonin as countermeasures for the physiological consequences of space flight.

Homeostatic response to sleep deprivation and circadian rhythmicity are intact in older adults with insomnia.

We examined whether homeostatic sleep drive and circadian rhythmicity differ in older adults with insomnia (OAI) compared to older good sleepers (GS). OAI (n = 37) and GS (n = 30) participated in a 60-h in-lab study with sleep deprivation and constant routine paradigms. Homeostatic sleep drive was assessed by examining the effect of sleep deprivation on delta EEG power and theta EEG power, and repeated sleep latency tests. Circadian rhythm was assessed with salivary melatonin (phase and amplitude), core body temperature (phase, amplitude, and mesor), and sleep latency during a constant routine paradigm. Mixed models were used to assess interactions of group (OAS vs GS) with homeostatic sleep and circadian effects. Compared to GS, OAI showed a greater linear increase in waking theta power during sleep deprivation, but the two groups did not show differential responses to sleep deprivation in delta EEG, or in repeated sleep latency tests. The two groups did not differ in circadian phase or amplitude of melatonin or core body temperature rhythms. OAI had a significantly elevated core body temperature mesor compared to GS. Homeostatic response to sleep deprivation was intact in OAI compared to GS; theta EEG power suggested a greater homeostatic response in OAI. Circadian rhythm amplitude and phase were similar in OAI compared to GS. Elevated body temperature mesor in OAI may indicate elevated physiological arousal. These findings suggest that effective treatments for insomnia in older adults may leverage intact sleep and circadian regulatory mechanisms, rather than repair defective sleep and circadian regulation.

A simple intervention for disorders of consciousness- is there a light at the end of the tunnel?

Sleep is a physiological state necessary for memory processing, learning and brain plasticity. Patients with disorders of consciousness (DOC) show none or minimal sign of awareness of themselves or their environment but appear to have sleep-wake cycles. The aim of our study was to assess baseline circadian rhythms and sleep in patients with DOC; to optimize circadian rhythm using an intervention combining blue light, melatonin and caffeine, and to identify the impact of this intervention on brain function using event related potentials. We evaluated baseline circadian rhythms and sleep in 17 patients with DOC with 24-h polysomnography (PSG) and 4-hourly saliva melatonin measurements for 48 h. Ten of the 17 patients (5 female, age 30–71) were then treated for 5 weeks with melatonin each night and blue light and caffeine treatment in the mornings. Behavioral assessment of arousal and awareness [Coma recovery scale-revised (CRS-R)], 24-h polysomnography and 4-hourly saliva melatonin measurements, oddball mismatch negativity (MMN) and subject's own name (SON) experiments were performed twice at baseline and following intervention. Baseline sleep was abnormal in all patients. Cosinor analysis of saliva melatonin results revealed that averaged baseline % rhythmicity was low (M: 31%, Range: 13–66.4%, SD: 18.4). However, increase in % Melatonin Rhythm following intervention was statistically significant (p = 0.012). 7 patients showed improvement of CRS-R scores with intervention and this was statistically significant (p = 0.034). All the patients who had improvement of clinical scores also had statistically significant improvement of neurophysiological responses on MMN and SON experiments at group level (p = 0.001). Our study shows that sleep and circadian rhythms are severely deranged in DOC but optimization is possible with melatonin, caffeine and blue light treatment. Clinical and physiological parameters improved with this simple and inexpensive intervention. Optimization of sleep and circadian rhythms should be integrated into rehabilitation programs for people with DOC.

Melatonin in razor clam Sinonovacula constricta: Examination of metabolic pathways, tissue distribution, and daily rhythms

Melatonin affects physiological processes that have circadian and seasonal cycles and causes behavioural changes in nearly all organisms, ranging from bacteria to mammals. However, no studies have focused on the presence, biosynthetic pathway, and rhythms of melatonin in bivalves, which are considered as the class of molluscs with the highest economic value. Here, the metabolic pathway and tissue distribution of melatonin, tissue transcription profiles of melatonin-related genes [key synthases arylalkylamine N-acetyltransferase type 2 and 5 (aanat2, aanat5), N-acetylserotonin methyltransferase (asmt), and melatonin receptor type 1 A1 and C3 (MTNR1A1, MTNR1C3)], daily changes in melatonin, transcripts of genes, and effects of four lights (blue, cyan, orange, and red) during the night on melatonin secretion were studied in a bivalve species, razor clam Sinonovacula constricta. Our results showed the presence of complete metabolic and circadian entrainment pathways of melatonin. The melatonin content in the lymphocytes and labial palp was higher than that in the other studied tissues, and aanat2, aanat5, asmt, MTNR1A1, and MTNR1C3 mRNA levels were the highest in the labial palp. Melatonin fluctuated rhythmically in lymphocytes and labial palps and increased at night. Similarly, aanat2, aanat5, asmt, MTNR1A1, and MTNR1C3 mRNA levels were rhythmic in the labial palp, peaking at night. In addition, blue light effectively inhibited the nocturnal secretion of melatonin in the clam. In summary, our results suggest that melatonin plays a role in light signal transduction and the circadian system in S. constricta.

Circadian and Neuroendocrine Basis of Photoperiodism Controlling Diapause in Insects and Mites: A Review.

The photoperiodic system is concealed in the highly complex black-box, comprising four functional subunits: 1) a photo/thermo-sensitive input unit, 2) a photoperiodic clock based on a circadian system, 3) a condenser unit counting the number of inductive signals, and 4) a neuroendocrine switch that triggers a phenotypic shift. This review aims to summarize the research history and current reach of our understanding on this subject to connect it with the molecular mechanism of the circadian clock rapidly being unveiled. The review also focuses on the mode of intersubunit information transduction. It will scan the recent advancement in research on each functional subunit, but special attention will be given to the circadian clock–endocrine conjunct and the role of melatonin signaling in the regulation of insect photoperiodism. Prothoracicotropic hormone (PTTH) probably plays the most crucial role in the regulation of pupal diapause, which is the simplest model system of diapause regulation by hormones investigated so far, particularly in the Chinese oak silkmoth (Antheraea pernyi). A search for the trigger to release the PTTH found some candidates, that is, indoleamines. Indolamine metabolism is controlled by arylalkylamine N-acetyltransferase (aaNAT). Indolamine dynamics and aaNAT enzymatic activity changed according to photoperiods. aaNAT activity and melatonin content in the brain showed not only a photoperiodic response but also a circadian fluctuation. aaNAT had multiple E-boxes, suggesting that it is a clock-controlled gene (ccg), which implies that cycle (cyc, or brain–muscle Arnt-like 1 = Bmal1)/Clock (Clk) heterodimer binds to E-box and stimulates the transcription of aaNAT, which causes the synthesis of melatonin. RNAi against transcription modulators, cyc, or Clk downregulated aaNAT transcription, while RNAi against repressor of cyc/Clk, per upregulated aaNAT transcription. Immunohistochemical localization showed that the circadian neurons carry epitopes of melatonin-producing elements such as aaNAT, the precursor serotonin, HIOMT, and melatonin as well as clock gene products such as cyc-ir, Per-ir, and dbt-ir, while PTTH-producing neurons juxtaposed against the clock neurons showed hMT2-ir in A. pernyi brain. Melatonin probably binds to the putative melatonin receptor (MT) that stimulates Ca2+ influx, which in turn activates PKC. This induces Rab 8 phosphorylation and exocytosis of PTTH, leading to termination of diapause. All the PTTH-expressing neurons have PKC-ir, and Rab8-ir. When diapause is induced and maintained under short days, serotonin binding to 5HTR1B suppresses PTTH release in a yet unknown way. RNAi against this receptor knocked out photoperiodism; short day response is blocked and diapause was terminated even under the short day condition. The result showed that a relatively simple system controls both induction and termination in pupal diapause of A. pernyi: the circadian system regulates the transcription of aaNAT as a binary switch, the enzyme produces a melatonin rhythm that gates PTTH release, and 5HTR1B and MT are probably also under photoperiodic regulation. Finally, we listed the remaining riddles which need to be resolved, to fully understand this highly complex system in future studies.

A Review of the Potential Effects of Melatonin in Compromised Mitochondrial Redox Activities in Elderly Patients With COVID-19.

Melatonin, an endogenous indoleamine, is an antioxidant and anti-inflammatory molecule widely distributed in the body. It efficiently regulates pro-inflammatory and anti-inflammatory cytokines under various pathophysiological conditions. The melatonin rhythm, which is strongly associated with oxidative lesions and mitochondrial dysfunction, is also observed during the biological process of aging. Melatonin levels decline considerably with age and are related to numerous age-related illnesses. The signs of aging, including immune aging, increased basal inflammation, mitochondrial dysfunction, significant telomeric abrasion, and disrupted autophagy, contribute to the increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These characteristics can worsen the pathophysiological response of the elderly to SARS-CoV-2 and pose an additional risk of accelerating biological aging even after recovery. This review explains that the death rate of coronavirus disease (COVID-19) increases with chronic diseases and age, and the decline in melatonin levels, which is closely related to the mitochondrial dysfunction in the patient, affects the virus-related death rate. Further, melatonin can enhance mitochondrial function and limit virus-related diseases. Hence, melatonin supplementation in older people may be beneficial for the treatment of COVID-19.

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.

Diabetes, Polycystic Ovarian Syndrome, Obstructive Sleep Apnea, and Obesity: A Systematic Review and Important Emerging Themes.

Type 2 diabetes mellitus (DM), polycystic ovarian syndrome (PCOS), obstructive sleep apnea (OSA), and obesity represent four large and growing patient populations. A great deal of scientific and clinical knowledge has been developed for them individually, and significant advancements made. Taken as a group, however, the interrelationships are not as well understood. The purpose of this systematic review is to identify the body of existing research that ties them together and then to identify and discuss the prevailing themes, particularly for cause-and-effect mechanisms. PubMed, Google Scholar, and ScienceDirect were used to identify systematic reviews and meta-analysis articles to establish the broadest reach. Initially, 434 articles were carefully screened, out of which 22 most relevant studies were reviewed. Five important themes were distilled from these papers based on continued and consistent emphasis in the literature. These themes include topics such as the importance of considering visceral obesity rather than Body Mass Index (BMI), the most effective treatment approaches, including mounting support for melatonin and circadian rhythm management, the results of OSA in its feed-forward contribution to hormone imbalance, the role of non-obesity-related risk factors to PCOS and OSA such as age and genetic predisposition, and growing evidence to suggest the importance of mental health as a comorbidity in addition to the more traditional ones such as cardiovascular pathology. A new framework for investigating the interaction across these four disorders is offered that includes a revised perspective on the specific role of PCOS, perhaps being further upstream relative to the others. There currently exists a lack of well-designed randomized controlled trials in this particular area of medicine, an endeavor we believe could result in significant value, particularly as it relates to treatment approaches.

0350 At-home Sample Collection for Measurement of Diurnal Rhythms of Urinary Cortisol and Melatonin

Abstract Introduction Sleep- and stress-related hormones (e.g., melatonin, cortisol) can be measured from dried urine samples collected at-home and sent for laboratory testing. These measures may be used to identify patterns of circadian alignment, peak nocturnal melatonin levels as well as a cortisol awakening response. The purpose of this analysis was to describe diurnal patterns and reference ranges from a 4-timepoint serial assessment of urinary cortisol and melatonin in a large cohort of at-home self collected samples. Methods This retrospective analysis evaluated data from 3,966 individuals who used an at-home Sleep and Stress Test (Everlywell, Inc.) between September 28, 2017 and July 14, 2021. Individuals provided four urine samples according to habitual sleep patterns: upon waking (T1), two hours after waking (T2), prior to the evening meal (T3), and at bedtime (T4). Melatonin and cortisol distributions were normalized to creatinine and log transformed to approximate normal distributions to define respective reference ranges (two standard deviations above and below the log transformed mean) and reverted to original units for reporting. Results 71% (n=2,832) of users were female and mean age was 42.8 (sd=12.0) years. Mean (sd) urinary values were as follows: Cortisol: T1, 29.3 (37.9) ug/g Cr; T2, 47.2 (49.8); T3, 14.9 (36.3); T4. 8.38 (26.9). Melatonin: T1, 745 (3208) ug/g Cr; T2, 169 (1189); T3, 45 (620); T4, 155 (1701). For cortisol, only 4-5% of samples fell outside the defined reference ranges across time points. Melatonin was more variable with 23% and 15% falling outside the reference range at time points T3 and T4, respectively. A majority of individuals’ peak cortisol occurred at T2 (67.4%), and melatonin at T1 (85.2%). Conclusion This analysis demonstrates measurable physiological diurnal patterns for cortisol and melatonin using at-home self-collection for dried urine tests. This provides evidence that at-home sample collection kits using dried urine spots are a viable tool for assessing diurnal patterns of sleep and stress. Future controlled studies are needed to evaluate the utility in identifying abnormal patterns associated with shift-work or sleep disorders. Support (If Any)

Incubation Temperature and Lighting: Effect on Embryonic Development, Post-Hatch Growth, and Adaptive Response.

During incubation, the content of the egg is converted into a chick. This process is controlled by incubation conditions, which must meet the requirements of the chick embryo to obtain the best chick quality and maximum hatchability. Incubation temperature and light are the two main factors influencing embryo development and post-hatch performance. Because chicken embryos are poikilothermic, embryo metabolic development relies on the incubation temperature, which influences the use of egg nutrients and embryo development. Incubation temperature ranging between 37 and 38°C (typically 37.5–37.8°C) optimizes hatchability. However, the temperature inside the egg called “embryo temperature” is not equal to the incubator air temperature. Moreover, embryo temperature is not constant, depending on the balance between embryonic heat production and heat transfer between the eggshell and its environment. Recently, many studies have been conducted on eggshell and/or incubation temperature to meet the needs of the embryo and to understand the embryonic requirements. Numerous studies have also demonstrated that cyclic increases in incubation temperature during the critical period of incubation could induce adaptive responses and increase the thermotolerance of chickens without affecting hatchability. Although the commercial incubation procedure does not have a constant lighting component, light during incubation can modify embryo development, physiology, and post-hatch behavior indicated by lowering stress responses and fearful behavior and improving spatial abilities and cognitive functions of chicken. Light-induced changes may be attributed to hemispheric lateralization and the entrainment of circadian rhythms in the embryo before the hatching. There is also evidence that light affects embryonic melatonin rhythms associated with body temperature regulation. The authors’ preliminary findings suggest that combining light and cyclic higher eggshell temperatures during incubation increases pineal aralkylamine N-acetyltransferase, which is a rate-limiting enzyme for melatonin hormone production. Therefore, combining light and thermal manipulation during the incubation could be a new approach to improve the resistance of broilers to heat stress. This review aims to provide an overview of studies investigating temperature and light manipulations to improve embryonic development, post-hatch growth, and adaptive stress response in chickens.

Light from heat lamps affects sow behaviour and piglet salivary melatonin levels

The light environment regulates animal physiology and behaviour. As widely used supplementary heat sources in creep areas, the effect of visible light radiated by infrared heat lamps on pigs is worth investigating. To investigate the effects of light from heat lamps on the behaviour of sows and piglets and possible endocrine mechanisms, 24 primiparous sows were randomly assigned to three supplementary heat source treatments: (1) 250 W non-luminous ceramic heat lamps (CE, n = 8), (2) 175 W red heat lamps (RL, n = 8), and (3) 175 W transparent heat lamps (TL, n = 8). All heat lamps were turned off on Day 15 postpartum. Piglets were weighed on days 3 and 21 postpartum. The number and duration of suckling within 24 h were analysed via video recordings on days 4, 8, and 16 postpartum. Sow posture changes during the day and night were detected using the YOLOv4 target detection network model. One marked piglet from six litters randomly selected from each treatment was used for saliva collection. Saliva samples were collected at 0800, 1400, 2000, and 0200 (+1 d) on days 10 and 20 postpartum. The results showed that the mean postural change frequency of TL sows was higher than that of CE sows (P < 0.05), while that of RL sows was not different from that of CE and TL sows. However, the duration of the sows being in each posture was not affected by the treatment. The total suckling duration of TL piglets was significantly longer than that of CE piglets, but there was no significant difference in the performance of the piglets. The melatonin concentrations in the saliva of piglets at 10 and 20 days of age in the three treatments showed different diurnal rhythms, but there was no significant difference in the levels of melatonin in TL piglets between night and day. Differences in salivary cortisol levels only appeared between the CE and RL groups at 20 days of age. Based on the present results, the illuminance and spectrum of the transparent heat lamps were sufficient to stimulate sow activity and inhibit melatonin levels in piglets. However, the stimulating effect on suckling was not sufficient to significantly improve the performance of piglets. Exposure to red heat lamps, rather than ceramic lamps, resulted in the strongest circadian rhythm of salivary melatonin in piglets.

Disturbances in melatonin, leptin and ghrelin rhythms in women with metabolic syndrome with and without polycystic ovary syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

A fixed single meal in the subjective day prevents free-running of the human sleep-wake cycle but not of the circadian pacemaker under temporal isolation.

Effects of a fixed single meal per day were examined on the circadian pacemaker and sleep-wake cycle in subjects under temporal isolation. When the time of single meal was allowed to take at any time of day (ad-lib meal), the sleep-wake cycle as well as the circadian rhythms in plasma melatonin, cortisol, and core body temperature were significantly phase-delayed in 8 days. On the other hand, when the time of meal was fixed at 1800 h in local time (RF meal), the phase-shift of sleep-wake cycle was not significant while those of the circadian rhythms were significant. The differential effects of a fixed single meal schedule were confirmed in most individual subjects. There was no evidence for the prefeeding increase in plasma cortisol and leptin levels under the fixed single meal schedule. The plasma ghrelin level was apparently high before meal in both ad-lib and RF meal groups, which was, however, likely sculptured by a nonspecific prandial drop and gradual increase after meal intake. Single meal augmented the prandial increase of plasma insulin levels by four to five times. These findings indicate that a single meal at a fixed time of the day during the subjective day failed to prevent the human circadian pacemaker but prevented the sleep-wake cycle from free running for at least 8 days under temporal isolation, suggesting that mealtime was a potent nonphotic time cue for the human sleep-wake cycle.

Unanticipated daytime melatonin secretion on a simulated night shift schedule generates a distinctive 24-h melatonin rhythm with antiphasic daytime and nighttime peaks.

The daily rhythm of plasma melatonin concentrations is typically unimodal, with one broad peak during the circadian night and near-undetectable levels during the circadian day. Light at night acutely suppresses melatonin secretion and phase shifts its endogenous circadian rhythm. In contrast, exposure to darkness during the circadian day has not generally been reported to increase circulating melatonin concentrations acutely. Here, in a highly-controlled simulated night shift protocol with 12-h inverted behavioral/environmental cycles, we unexpectedly found that circulating melatonin levels were significantly increased during daytime sleep (p < .0001). This resulted in a secondary melatonin peak during the circadian day in addition to the primary peak during the circadian night, when sleep occurred during the circadian day following an overnight shift. This distinctive diurnal melatonin rhythm with antiphasic peaks could not be readily anticipated from the behavioral/environmental factors in the protocol (e.g., light exposure, posture, diet, activity) or from current mathematical model simulations of circadian pacemaker output. The observation, therefore, challenges our current understanding of underlying physiological mechanisms that regulate melatonin secretion. Interestingly, the increase in melatonin concentration observed during daytime sleep was positively correlated with the change in timing of melatonin nighttime peak (p = .002), but not with the degree of light-induced melatonin suppression during nighttime wakefulness (p = .92). Both the increase in daytime melatonin concentrations and the change in the timing of the nighttime peak became larger after repeated exposure to simulated night shifts (p = .002 and p = .006, respectively). Furthermore, we found that melatonin secretion during daytime sleep was positively associated with an increase in 24-h glucose and insulin levels during the night shift protocol (p = .014 and p = .027, respectively). Future studies are needed to elucidate the key factor(s) driving the unexpected daytime melatonin secretion and the melatonin rhythm with antiphasic peaks during shifted sleep/wake schedules, the underlying mechanisms of their relationship with glucose metabolism, and the relevance for diabetes risk among shift workers.

Circadian Disruption of Melatonin among Night Shift Workers and Its Effect on Glycemic Variability

Melatonin is a pineal gland secreted hormone controlling sleep wakefullness. Light is a stimulus and hence this hormone exhibits circadian rhythm. Melatonin has pleiotropic effects on carbohydrate and lipid metabolisms. Glycemic variability is defined as variations in interstitial glucose levels measured every 15 seconds using a sensor-based technique. It is the result of constant carbohydrate metabolism and insulin action. Melatonin also has rhythms that are more akin to a nocturnal hormone. It affects glycemic variability. Variability is associated with a very high cardiac risk factor. Melatonin rhythm may be disrupted in night shift workers as a result of light exposure during the night, with implications for insulin secretion and glycemic variability. Correlation provides greater insight into the rhythmic hormonal activity and altered glucose homeostasis that predispose to diabetes, and thus this study was done to establish the correlation. This study was done to evaluate the effect of melatonin levels on altering glycemic control among night shift workers. This case control study included 40night shift workers both male and female (cases) aged 25-35years and 40 healthy controls of same age group. Blood samples for melatonin estimation were collected at 9PM and 6AM (after night shift work) by venepuncture and serum separated. Serum melatonin levels were estimated by ELISA method. Fasting and post prandial blood glucose were estimated by GOD-POD method and glycemic variability analyzed by Abbott biosensors. Data was analyzed using SPSS package. Night shift workers were found to have decreased melatonin levels and altered blood glucose levels compared to the control group. Melatonin has a negative influence on glycemic variability. This fact was evidenced in our study. Hence this study will help us to understand and intervene.

Blue light exposure increases functional connectivity between dorsolateral prefrontal cortex and multiple cortical regions.

ObjectiveBlue light is a powerful environmental stimulus that can produce significant phase shifts in the circadian rhythm of melatonin and sleep propensity as well as acute effects on alertness of neurobehavioral performance. Here, we undertook an expansion and reanalysis of our previously published findings to examine the effect of acute blue light exposure on the strength of resting-state functional connectivity (rsFC) between a previously identified region of the left dorsolateral prefrontal cortex (DLPFC) and 106 cortical and subcortical regions.MethodsTwenty-nine healthy adults (16 men and 13 women; age 18–32 years) completed a psychomotor vigilance test (PVT) before and after a single 30-min exposure to either blue (λ = 469 nm; n = 17) or amber wavelength (λ = 578 nm; n = 12) light, immediately followed by an rsFC scan.ResultsCompared with amber light, blue light exposure produced significantly greater functional connectivity between the left DLPFC seed region and 30 cortical and subcortical regions (P < 0.05; false discovery rate–corrected). Although neurobehavioral performance did not differ between light conditions, only those exposed to blue light showed a significant association between rsFC and sustained PVT performance. Better sustained PVT performance was associated with greater connectivity between the left DLPFC and regions associated with visuospatial awareness/motion detection (right temporal-occipital middle temporal gyrus) and memory (left hippocampus), as well as reduced connectivity in a circuit associated with cognitive rumination and distraction (left parahippocampal gyrus).ConclusionFindings suggest that blue-wavelength light may facilitate acute alertness and improved cognitive performance through enhanced rsFC between the left DLPFC and cortical regions associated with visuospatial awareness.

Effect of blue and red monochromatic light during incubation on the early post-embryonic development of immune responses in broiler chicken

ABSTRACT 1. The light regime during incubation can influence embryonic and post-embryonic life and its effects can be mediated by rhythmic melatonin production in the embryonic pineal gland. 2. This study explored whether the incubation of chick embryos under red or blue monochromatic light, which induces maximum and minimum melatonin production, respectively, can influence the development and reactivity of the immune system in chicks. 3. In hatchlings, basal expression of immune genes (AvBD-1, PSEN-1, and IL-6) was evaluated in the duodenum using real-time PCR. The expression of these genes was measured weekly for three weeks after hatching, 3 h after intraperitoneal lipopolysaccharide (LPS) injection. At these times, the heterophil/lymphocyte ratio (He/Ly) was evaluated on blood smears, plasma immunoglobulin Y (IgY) concentrations by ELISA and IL-6 gene expression in the spleen by real-time PCR were determined. 4. During development, the He/Ly ratio and plasma IgY concentration were not significantly influenced by the light quality during incubation. Red light increased gene expression of AvBD-1 in hatchlings and IL-6 in two-week-old chickens compared to birds incubated under blue light. The expression of IL-6 after LPS stimulation increased in an age-dependent manner, both in the duodenum and the spleen, reflecting the maturation of the immune system. 5. The results suggested that red light may increase the local immune response in the gut immediately after hatching, but this effect was not apparent during later development.

Melatonergic agents influence the sleep-wake and circadian rhythms in healthy and psychiatric participants: a systematic review and meta-analysis of randomized controlled trials

Exogenous melatonergic agents are widely used to treat insomnia and sleep disturbance. Several studies have shown that they might also modulate circadian rhythms. The purpose of this systematic review and meta-analysis was to summarize current knowledge about the effects of melatonin supplements and melatonin agonists on the sleep-wake cycle as well as on the circadian rhythm of melatonin in healthy participants and in patients with psychiatric disorders. The following electronic databases were searched: EMBASE, PubMed, Web of Science, CINAHL, and Cochrane Library. Of the 12,719 articles, we finally selected 30 studies including 1294 healthy participants and 8 studies including 687 patients with psychiatric disorders. Cochrane risk of bias tool was used to assess the risk of bias. Using meta-ANOVA, studies on healthy participants showed advancing effects of melatonergic supplements and agonists on sleep-wake cycle according to dosing time and dosage, despite the fact that the original individual melatonin rhythm was within a normal range (fixed effect model standardized mean difference [95% Confidence Interval] = −0.639[−0.968 to −0.310]). In a limited number of randomized controlled trials with psychiatric patients, the findings seemed similar to those with healthy participants, despite the psychiatric disorders and treatment related factors affecting circadian rhythms. Given the unmet clinical need for evidence-based treatments to correct circadian rhythms in psychiatric disorders, efficacy of melatonergic agents seen in healthy participants, and similarity of findings among psychiatric patients, large scale, well-designed randomized controlled trials are needed to test efficacy on circadian parameters in psychiatric disorders.

Exploring the Role of Melatonin in Meditation on Cardiovascular Health

Cardiovascular diseases are the leading cause of disease burden globally. Sleep and cardiovascular connection represent a two-way lane. Recently, many reports have suggested that meditation practices have a beneficial effect on cardiovascular diseases. But the exact mechanism was not known. Several reports suggest that meditation induces the secretion of melatonin. The rhythm of melatonin follows a sleep pattern. Thus, the present hypothesis correlates the plausible mechanisms involved in meditation with enhancing cardiac health through melatonin synthesis. An altered modern lifestyle decreases the level of melatonin which disrupts the circadian rhythm, and subsequently, there is a high incidence of cardiovascular diseases. The disrupted cardiac energy metabolism is distorted due to altered circadian rhythm with elevated ROS. The increased level of ROS activates the inflammatory mediators' cytokines and damages the DNA, resulting in altered cardiac physiology. Melatonin regulates the circadian rhythm and acts as a silent regulator for the cardiac energy balance. Melatonin is the central player of circadian rhythm, and it protects cardiomyocytes by acting as an antioxidant, anti-inflammatory mediator, and repairing DNA damage. Meditation induces melatonin and improves cardiac health through the aforementioned mechanisms.