Melatonin Secretion Research Articles

Melatonin, circadian rhythms and breast cancer

Breast cancer (BC) is the leading cause of morbidity and mortality of malignant neoplasms in women worldwide. In spite of a large number of studies devoted to the etiopathogenesis of this group of malignant tumors, many questions concerning specific mechanisms of their origin and development are still unresearched. Based on numerous studies in recent years, in addition to traditional risk factors (such as hereditary factors, hormonal disorders, environmental factors, etc.), foreign and Russian authors have identified a new risk factor for BC development - the sphere of molecular disorders affecting circadian rhythms and circadian genes, as well as metabolic and regulatory intracellular pathways regulated by them. It has been shown that the balance between oncogenes and suppressor genes and processes such as neoangiogenesis, metastasis and antitumor immune response depend on the functioning of the circadian rhythm system. One of the key metabolites in the circadian rhythm regulation system is melatonin, which physiological effects extend not only to the central nervous system, but also to peripheral tissue cells. The study of the relationship between circadian rhythm disturbances, melatonin secretion and malignant tumors is one of the important tasks of modern oncology. In the present review the following aspects of this problem are considered in detail: relationships between circadian rhythms, melatonin and BC; molecular mechanisms of melatonin antitumor action in BC; therapeutic potential of melatonin in prevention and treatment of malignant breast tumors as a direct antitumor agent, a component of accompanying treatment, and as a radiosensitizer and radioprotector for radiotherapy. The purpose of this review is to investigate the problem of the relationship between the circadian rhythm system, melatonin and molecular mechanisms of development and progression of breast malignancies, as well as the therapeutic potential of melatonin in their prevention and treatment. The review is based on the study of relevant and reliable scientific articles, reviews, meta-analyses, systematic reviews, and clinical trials published in Scopus, PubMed, Web of Science and in peer-reviewed Russian journals mainly during the last 5 years.

Reproductive performance of hair ewes and rams implanted with melatonin previous to the anestrus season in northwest Mexico.

Ovine reproductive behavior depends on annual photoperiodic cycle and its impact on endogenous melatonin secretion. In this regard, exogenous melatonin administration previous to the physiological anestrus period could modify the reproductive performance of sheep in the northwest of Mexico. Two independent studies were performed to evaluate such hypothesis in hair sheep implanted with melatonin prior to the anestrus season in latitudes 24° and 25° of Mexico. Study 1 involved 15 rams assigned to one of three treatments receiving 0mg (n=5), 18mg (n=5), or 36mg (n=5) of melatonin subcutaneously. Study variables were measured monthly since implantation (d0) and included testosterone concentration, scrotal circumference, mass motility, individual motility, and sperm concentration. Study 2 included 50 ewes assigned to one of two treatments receiving 0mg (n=25) or 18mg (n=25) of melatonin subcutaneously. In ewes, progesterone concentration and the frequency of females in anestrus were measured during the implantation (-30d), as well as at the beginning (0d) and at the end (45d) of the mating period, while pregnancy rate was determined by ultrasonography 45d after. Continuous variables were analyzed using a mixed effects model considering treatment, time, and the treatment by time interaction as fixed effects. Animal nested within treatment was the random effect. Binary variables were analyzed using the chi-square test. In males, melatonin improved testosterone and sperm concentrations (P<0.05), while in females, a 28% higher pregnancy rate was observed in implanted ewes (P<0.05). Therefore, melatonin enhanced reproductive parameters in both sexes and its exogenous administration previous to the anestrus season in northwest Mexico could be more effective in rams.

Impaired Melatonin Secretion, Oxidative Stress and Metabolic Syndrome in Night Shift Work.

Metabolic syndrome has been associated in many studies with working in shifts. Even if the mechanistic details are not fully understood, forced sleep deprivation and exposure to light, as happens during night shifts, or irregular schedules with late or very early onset of the working program, lead to a sleep-wake rhythm misalignment, metabolic dysregulation and oxidative stress. The cyclic melatonin secretion is regulated by the hypothalamic suprachiasmatic nuclei and light exposure. At a central level, melatonin promotes sleep and inhibits wake-signals. Beside this role, melatonin acts as an antioxidant and influences the functionality of the cardiovascular system and of different metabolic processes. This review presents data about the influence of night shifts on melatonin secretion and oxidative stress. Assembling data from epidemiological, experimental and clinical studies contributes to a better understanding of the pathological links between chronodisruption and the metabolic syndrome related to working in shifts.

The use of melatonin preparations in sleep disorders

The role in the body and the biological significance of the pineal hormone melatonin is discussed. Data are presented on the effect on biological rhythms in humans and animals, as well as on the sleep in general. In diurnal humans and animals, melatonin acts on the suprachiasmatic nuclei of the hypothalamus to dampen the wake-stimulating signal of the internal clock, thereby promoting sleep. Data are presented on the clinical use of melatonin in sleep disorders: Circadian Rhythm Sleep-Wake Disorders (jet lag syndrome, delayed sleep phase syndrome, irregular cycle), parasomnias (Rapid-Eye Movements Sleep Behavior Disorder) and insomnia. A significant effect of melatonin preparations with a high level of evidence was confirmed in Circadian Rhythm Sleep-Wake Disorders, less pronounced in Parasomnias. The effects of melatonin, used as a drug for jet lag, have the greatest degree of evidence. The melatonin preparation is recommended to be taken both before the flight and at the new place of stay in accordance with the time of its evening secretion in this time zone. In delayed sleep phase syndrome, the onset of melatonin secretion is delayed, reflecting a general lag in the body’s internal clock. Taking melatonin preparations leads to a shift in the sleep-wake cycle to an earlier time. In REM sleep behavior disorder, melatonin preparations to reduce excessive motor activity are preferred over benzodiazepines, since this disorder manifests itself in people of older age groups, and an undesirable effect on cognitive functions should be avoided. In chronic insomnia, the effect of melatonin significantly exceeds the placebo effect and is most pronounced in people of older age groups.

Alterations of Gut-Derived Melatonin in Neurobehavioral Impairments Caused by Zinc Oxide Nanoparticles.

The widespread use of zinc oxide nanoparticles (ZnONPs) has raised concerns about its potential toxicity. Melatonin is a neurohormone with tremendous anti-toxic effects. The enterochromaffin cells are an essential source of melatonin in vivo. However, studies on the effects of ZnONPs on endogenous melatonin are minimal. In the present study, we aimed to investigate the effects of ZnONPs exposure on gut-derived melatonin. In the present study, 64 adult male mice were randomly and equally divided into four groups, and each group was exposed to ZnONPs (0, 6.5, 13, 26 mg/kg/day) for 30 days. Subsequently, the neurobehavioral changes were observed. The effects of ZnONPs on the expression of melatonin-related genes arylalkylamine N-acetyltransferase (Aanat), melatonin receptor1A (Mt1/Mtnr1a), melatonin receptor1B (Mt2/Mtnr1b), and neuropeptide Y (Npy) on melatonin synthesis and secretion in duodenum, jejunum, ileum and colon during day and night were also assessed. The results revealed that oral exposure to ZnONPs induced impairments of locomotor activity and anxiety-like behavior in adult mice during the day. The transcriptional analysis of brain tissues revealed that exposure to ZnONPs caused profound effects on genes and transcriptional signaling pathways associated with melatonin synthesis and metabolic processes during the day and night. We also observed that, in the duodenum, jejunum, ileum and colon sites, ZnONPs resulted in a significant reduction in the expression of the gut-derived melatonin rate-limiting enzyme Aanat, the membrane receptors Mt1 and Mt2 and Npy during the day and night. Taken together, this is the first study shows that oral exposure to ZnONPs interferes with melatonin synthesis and secretion in different intestinal segments of adult mice. These findings will provide novelty insights into the neurotoxic mechanisms of ZnONPs and suggest an alternative strategy for the prevention of ZnONP neurotoxicity.

A Study on the Effect and Prevention of Blue Light on Eyes

Abstract: In recent years, large number of people complaining about rteh effects of light pollution on their eyes. Blue light with the wavelength range between 415nm and 455nm is much nearly related with eye damage in the visible range. High energy blue light damages the hormonal balance and negatively impacts sleep quality by passing from the cornea to retina. Here it led to many types of disease such as cataract, age related degeneration and dry eye. It also stimulates the brain, inhibits melatonin secretion, and increases the production of adrenocortical hormones. Consequently, the impact of Blu-rays on the eye is growing in significance going forward. The effects of blue light on ocular tissues are highlighted in this study, along with a summary of the studies on eye injuries, physical preventative measures, and medical care.

Regulation of Aqueous Humor Secretion by Melatonin in Porcine Ciliary Epithelium.

Secretion of melatonin, a natural hormone whose receptors are present in the ciliary epithelium, displays diurnal variation in the aqueous humor (AH), potentially contributing to the regulation of intraocular pressure. This study aimed to determine the effects of melatonin on AH secretion in porcine ciliary epithelium. The addition of 100 µM melatonin to both sides of the epithelium significantly increased the short-circuit current (Isc) by ~40%. Stromal administration alone had no effect on the Isc, but aqueous application triggered a 40% increase in Isc, similar to that of bilateral application without additive effect. Pre-treatment with niflumic acid abolished melatonin-induced Isc stimulation. More importantly, melatonin stimulated the fluid secretion across the intact ciliary epithelium by ~80% and elicited a sustained increase (~50-60%) in gap junctional permeability between pigmented ciliary epithelial (PE) cells and non-pigmented ciliary epithelial (NPE) cells. The expression of MT3 receptor was found to be >10-fold higher than that of MT1 and MT2 in porcine ciliary epithelium. Aqueous pre-treatment with MT1/MT2 antagonist luzindole failed to inhibit the melatonin-induced Isc response, while MT3 antagonist prazosin pre-treatment abolished the Isc stimulation. We conclude that melatonin facilitates Cl- and fluid movement from PE to NPE cells, thereby stimulating AH secretion via NPE-cell MT3 receptors.

Effects of low dose radiation on behavior rhythm of zebrafish (Danio rerio)

Biological rhythm refers to the internal regulation of various life activities of an organism, which are determined by the specific time structure sequences of each individual. Behavior rhythm is the most intuitive embodiment of biological rhythm. To study the effect of low dose radiation on behavioral rhythm, zebrafish (Danio rerio) was used as a model organism in this study. The early embryos of zebrafish were irradiated at doses of 0.01, 0.1, and 1 Gy to observe the changes in zebrafish development, circadian rhythm, key clock genes, related RNA and protein expression, and melatonin. The results revealed that 0.1 and 1 Gy radiation could lead to different degrees of telencephalic nerve cell apoptosis and the formation of vacuolar structures. 0.1 and 1 Gy radiation could reduce the hatching rate of zebrafish embryos at 72 hpf and delay embryo hatching. The analysis of circadian behavior at 120 hpf demonstrated that 1 Gy dose of radiation altered the circadian rhythm of zebrafish, as well as decreased the distance, amplitude, and phase of movement. RT-PCR analysis of the key clock genes (bmal1b, clock1a, per1b, per2, cry2, and nr1d1) involved in regulating circadian rhythm was performed. The results showed that 1 Gy radiation could interfere with the expression of clock genes in zebrafish embryos and upregulate bmal1b, clock1a, and per1b. Western blot experiments further verified the protein expression of key clock genes, bmal1b and clock. Detection of melatonin secretion at different time points over 24 h showed that radiation doses of 0.1 and 1 Gy could increase melatonin secretion. Based on these findings, it is speculated that a certain dose of radiation may affect melatonin secretion, which impacts the telencephalon structure and ontogeny of zebrafish, delays hatching, and changes the circadian rhythm. This effect is thought to be achieved through upregulating the expression of circadian rhythm genes, clock1a and per1b and related proteins, which may be responsible for the abnormal circadian rhythm caused by radiation.

Long-term artificial/natural daytime light affects mood, melatonin, corticosterone, and gut microbiota in rats

The desynchronization of circadian rhythms affected by light may induce physiological and psychological disequilibrium. We aimed to elucidate changes of growth, depression-anxiety like behaviors, melatonin and corticosterone (CORT) secretion, and gut microbiota in rats influenced by long-term light inputs. Thirty male Sprague-Dawley rats were exposed to a 16/8h light/dark regime for 8weeks. The light period was set to 13h of daylight with artificial light (AL group, n = 10), or with natural light (NL group, n = 10), or with mixed artificial-natural light (ANL group, n = 10), and 3h of artificial night light after sunset. The obtained findings indicated that the highest weight gain and food efficiency were observed in the AL group and the lowest in NL group. In the behavioral tests, the NL and ANL groups showed lower anxiety level than AL group, and ANL groups showed lower depression level than AL group. The NL and ANL groups had delayed acrophases and maintained higher concentrations of melatonin compared to AL group. The circadian rhythm of CORT was only found in ANL group. At the phylum level, the mixed light contributed to a lower abundance of Bacteroidetes. The genus level results recommend a synergistic effect of artificial light and natural light on Lactobacillus abundance and an antagonistic effect on the Lachnospiraceae_NK4A136_group abundance. The study indicated that the mixture of artificial and natural light as well as the alignment of the proportions had beneficial influences on depression-anxiety-like levels, melatonin and corticosterone secretion, and the composition of the gut microbiota. KEY POINTS: • The mixed light can reduce the depression-anxiety level • The mixed light can maintain the secretion rhythm of melatonin and CORT • The mixed light can increase Lactobacillus and decrease Lachnospiraceae_NK4A136_group.

Benson's Relaxation Techniques to Improve Sleep Quality in Diabetes Mellitus Patients

The sleep pattern of diabetics are disturbed because they often wake up and have difficulty going back to sleep. This study aimed to determine the effect of Benson’s relaxation technique on the sleep quality of clients with diabetes mellitus at the Polowijen Health Center. This research design used Pre-Experimental One Group pre-post design. The sample in this study was 30 people with diabetes mellitus with poor sleep quality. The research instrument used was a sleep quality questionnaire. The study was conducted from 1st July to 7th August 2019. Data were analysed with the T-Dependent test (Paired Sample T Test). The results of this study indicated that there is an effect of the Benson relaxation technique on the sleep quality of diabetes mellitus patients, with the average total score after the Benson relaxation technique being 18.83 and the results of the T-Dependent statistical test (Paired Sample T Test) was a Sig.2 Tailed 0.000. Benson’s relaxation technique accelerates a comfortable and relaxed condition. As a result, the secretion of catecholamine and cortisol hormones inhibits the production of endorphins, enkephalins, and serotonin increases, the stimulation of the Reticular Activating System (RAS) decreases, then the secretion of the hormone melatonin increases when the brain is relaxed, and the Bulbar Synchronizing Regional (BSR) is active, causing a person to fall asleep.&#x0D; Keywords: sleep quality, diabetes mellitus, Benson relaxation technique

Meiosis-mediated reproductive toxicity by fenitrothion in Caenorhabditis elegans from metabolomic perspective

Fenitrothion (FNT), an organophosphorus insecticide, is widely detected in the living environment. The reproductive and endocrine toxicity of FNT to biological communities has been ever reported, but potential mechanism and reproductive toxicity dose effect remain unclear. In our study, we constructed Caenorhabditis elegans model to analyze the reproductive toxicity mechanism of FNT based on metabolomics and evaluated its reproductive toxicity dose effect using benchmark dose (BMD)method. Our results showed that FNT exposure significantly reduced brood size, number of germ cells, and delayed gonadal development in nematodes. Non-targeted metabolomics revealed that FNT exposure caused significant metabolic disturbances in nematodes, leading to a significant reduction in the synthesis of cortisol and melatonin, and the latter played a mediating role in the effects of FNT on number of germ cells. We further found that the levels of these two hormones were significantly negative correlated with the expression of the androgen receptor nhr-69 and affected the meiosis of germ cells by regulating the nhr-69/ fbf-1/2 /gld-3 /fog-1/3 pathway. Meanwhile, the study found the BMDL10s for N2 and him-5 mutant were 0.411 μg/L by number of germ cells and 0.396 μg/L by number of germ cells in the meiotic zone, respectively, providing a more protective reference dose for ecological risk assessment of FNT. This study suggested that FNT can affect androgen receptor expression by inhibiting cortisol and melatonin secretion, which further mediate the meiotic pathway to affect sperm formation and exert reproductive toxicity, and provides a basis for setting reproductive toxicity limits for FNT.

THE ROLE OF MELATONIN IN COMPLICATED PREGNANCY

In recent years, there have been signifi cant changes in the understanding of the hormone melatonin (MT). It has been confi rmed that the processes of conception, pregnancy, and childbirth directly depend on the rhythm and level of MT secretion, but there is no general concept that could describe in detail the mechanisms of infl uence on ontogenesis. The aim of the study. To assess MT in the blood of pregnant with retrochorial hematoma (RCH) up to 12 weeks of pregnancy.Material and methods. Two groups were formed: 1st – 40 pregnant women with RCH, 2nd control– 44 healthy pregnant. Obstetric research, enzyme immunoassay to determine MT, and ultrasound were performed. Statistical analysis according to generally accepted methods of variational statistics.The approval of the scientifi c work was obtained from the Bioethical Commission of the Bukovinian State Medical University (Ukraine).Research results. A signifi cant decrease of MT in the 1st group and the dependence of its level on the size of the RCH was revealed: in the case of hematomas up to 1 cm MT (59.31±10.32 pg/ml) (р ˂ 0.001), which is not observed in hematomas more than 1 cm, which are dangerous for pregnancy (93.98±14.52 pg/ml), which may indicate a compensatory increase in MT; and the term of pregnancy (in 10-12 weeks 79.03±9.61 pg/ml (р ˂ 0.05), in 5-6 weeks 93.78±17.44 pg/ml).Conclusions. In cases of RCH up to 1 cm the number of MT decreases with the development of pregnancy, which can be used as a prognostic marker for the diagnosis of pregnancy complications. The increase in the level of MT with RCH more than 1 cm can be considered as a compensatory increase for the preservation of pregnancy and a regulatory infl uence on the further course of pregnancy.

The dim light melatonin onset across ages, methodologies, and sex and its relationship with morningness/eveningness.

The onset of melatonin secretion, the dim light melatonin onset (DLMO), is a tool for determining the phase of the circadian timing system. Although small studies have investigated the impacts of age and methods of calculating DLMO, there is no DLMO reference range. In the current study, the saliva DLMO from 3579 participants from 121 published studies and plasma DLMO from 818 healthy controls from 31 studies (aged 3-73 years) were analyzed. In a subset of 53 papers (1749 participants), individual saliva DLMO and Morningness Eveningness Questionaire (MEQ) scores were obtained from authors or mined from publications and a reference range was constructed. Saliva DLMO was earliest in children to 10 years of age and latest around 20 years of age and thereafter advanced with age by 30 min in the oldest participants. Melatonin assay methods and DLMO calculation methods had little effect on the determination of the DLMO. Saliva DLMO was correlated (p < 0.001) with the MEQ score; lower MEQ scores were associated with later DLMO. MEQ scores increased with age, reflecting a tendency toward morningness. An evaluation of 14 saliva DLMO studies of clinically diagnosed patients living with delayed sleep-wake phase disorder (mean ages 20 to 31 years) revealed mean saliva DLMO within the reference range albeit at the late extreme. Peak plasma melatonin levels from 179 studies of healthy participants revealed a high degree of variability within studies and age groups, but only a small decline between the 20 and 50 years and lowest levels after 70 years.

Structural properties and binding mechanism of DNA aptamers sensing saliva melatonin for diagnosis and monitoring of circadian clock and sleep disorders

Circadian desynchrony with the external light-dark cycle influences the rhythmic secretion of melatonin which is among the first signs of circadian rhythm sleep disorders. An accurate dim light melatonin onset (established indicator of circadian rhythm sleep disorders) measurement requires lengthy assays, and antibody affinities alterations, especially in patients with circadian rhythm disorders whose melatonin salivary levels vary significantly, making antibodies detection mostly inadequate. In contrast, aptamers with their numerous advantages (e.g., target selectivity, structural flexibility in tuning binding affinities, small size, etc.) can become preferable biorecognition molecules for salivary melatonin detection with high sensitivity and specificity. This study thoroughly characterizes the structural property and binding mechanism of a single-stranded DNA aptamer full sequence (MLT-C-1) and its truncated versions (MLT-A-2, MLT-A-4) to decipher its optimal characteristics for saliva melatonin detection. We use circular dichroism spectroscopy to determine aptamers’ conformational changes under different ionic strengths and showed that aptamers display a hairpin loop structure where few base pairs in the stem play a significant role in melatonin binding and formation of aptamer stabilized structure. Through microscale thermophoresis, aptamers demonstrated a high binding affinity in saliva samples (MLT-C-1F Kd = 12.5 ± 1.7 nM; MLT-A-4F Kd = 11.2 ± 1.6 nM; MLT-A-2F Kd = 2.4 ± 2.8 nM; limit-of-detection achieved in pM, highest sensitivity attained for MLT-A-2F aptamer with the lowest detection limit of 1.35 pM). Our data suggest that aptamers are promising as biorecognition molecules and provide the baseline parameters for the development of an aptamer-based point-of-care diagnostic system for melatonin detection and accurate profiling of its fluctuations in saliva.

Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders.

Melatonin is ubiquitous molecule with wide distribution in nature and is produced by many living organisms. In human beings, pineal gland is the major site for melatonin production and to lesser extent by retina, lymphocytes, bone marrow, gastrointestinal tract, and thymus. Melatonin as a neurohormone is released into circulation wherein it penetrates all tissues of the body. Melatonin synthesis and secretion is supressed by light and enhanced by dark. Melatonin mostly exerts its effect through different pathways with melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) being the predominant type of receptor that are mainly expressed by many mammalian organs. Melatonin helps to regulate sleep patterns and circadian rhythms. In addition, melatonin acts as an antioxidant and scavenges excessive free radicals generated in the body by anti-excitatory and anti-inflammatory properties. A multiple array of other functions are displayed by melatonin that include oncostatic, hypnotic, immune regulation, reproduction, puberty timing, mood disorders, and transplantation. Deficiencies in the production or synthesis of melatonin have been found to be associated with onset of many disorders like breast cancer and neurodegenerative disorders. Melatonin could be used as potential analgesic drug in diseases associated with pain and it has quite promising role there. In the past century, a growing interest has been developed regarding the wide use of melatonin in treating various diseases like inflammatory, gastrointestinal, cancer, mood disorders, and others. Several melatonin agonists have been synthesized and are widely used in disease treatment. In this review, an effort has been made to describe the biochemistry of melatonin along with its therapeutic potential in various diseases of humans.

Analysis of MTNR1A Genetic Polymorphisms and Their Association with the Reproductive Performance Parameters in Two Mediterranean Sheep Breeds.

Sheep farming plays an important economic role, and it contributes to the livelihoods of many rural poor in several regions worldwide and particularly in Tunisia. Therefore, the steady improvement of ewes' reproductive performance is a pressing need. The MTNR1A gene has been identified as an important candidate gene that plays a key role in sheep reproduction and its sexual inactivity. It is involved in the control of photoperiod-induced seasonality mediated by melatonin secretion. The aim of this study was to identify SNPs in the MTNR1A gene in two Tunisian breeds, Barbarine (B) and Queue Fine de l'Ouest (QFO). DNA extracted from the blood of 77 adult ewes was sequenced. Selected ewes were exposed to adult fertile rams. A total of 26 SNPs were detected; 15 SNPs in the promoter region and 11 SNPs in the exon II were observed in both (B) and (QFO) breeds. The SNP rs602330706 in exon II is a novel SNP detected for the first time only in the (B) breed. The SNPs rs430181568 and rs40738822721 (SNP18 and SNP20 in our study, respectively) were totally linked in this study and can be considered a single marker. DTL was associated with SNP18 and SNP20 in (B) ewes (p < 0.05); however, no significant difference was detected between the three genotypes (G/G, G/A, and A/A) at these two SNPs. Fertility rate and litter size parameters were not affected by SNP18 and SNP20. There was an association between these two polymorphisms and (B) lambs' birth weights (p < 0.05). Furthermore, the ewes with the A/A genotype gave birth to lambs with a higher weight compared to the other two genotypes for this breed (p < 0.05). There was not an association between SNP 18 and SNP20 and (QFO) ewes' reproductive parameters. These results might be considered in future sheep selection programs for reproductive genetic improvement.

Methylation of melatonin receptors in patients with unipolar and bipolar depression

Disturbances of melatonin secretion alter the circadian rhythm and sleep-wake cycle, which is observed among patients with depression. Melatonin acts via melatonin receptors MT1 and MT2, which are present in many tissues, including peripheral blood mononuclear cells (PBMC). We assume that disturbances of the melatonin pathway in the brain may be reflected by molecular changes in peripheral organs. The study objective was to evaluate the methylation profile of CpG island in the promoter region of melatonin receptor genes MTNR1A and MTNR1B in PBMC of patients with depression and compare it with healthy volunteers. The study group comprised 85 patients with unipolar (UP) and bipolar disorders (BP) and 83 controls. The methylation pattern of CpG island in the promoter region was analyzed using the quantitative methylation-specific real-time PCR (qMSP-PCR) method. We found that the methylation profile of the patients with depression varied in comparison to the control group. The methylation level of MTNR1A was significantly lower among depressed patients compared to controls. Additionally, melatonin concentration was negatively correlated with MTNR1B methylation level among the UP patients. The study may suggest that the methylation profile of melatonin receptors in PBMC may be used as a complementary molecular marker in depression diagnosis.

Massage stimulation’s effect on melatonin levels in preterm infants via vagal activity

Massage stimulation has been suggested to be used to promote the growth and development of preterm and low birth weight (LBW) infants. Some experts believe that infant massage can help develop the central nervous system, which increases vagal activity, improves hormone secretion, triggers the release of melatonin, and increases its production. Rhythmic endogenous melatonin secretion appears in term infants around 2-3 months of age, whereas preterm infants have delayed melatonin secretion, which persists after correction for 8 to 9 months of gestation. Massage stimulation increases vagal activity, which causes an increase in melatonin. Vagal activity then modulates pineal and extrapineal activity, resulting in melatonin production. Based on scientific evidence, current reviews suggest that massage stimulation can provide health benefits to newborns, particularly preterm infants. This article aims to review that massage stimulation can increase melatonin levels by activating vagal mechanisms.

Validation of the Self-Rating of Biological Rhythm Disorder for Adolescents (SBRDA) Scale by Dim Light Melatonin Onset in Healthy Young Adults.

Understanding the biological rhythms that influence young adult health is vital because the combination of biological changes and a circadian phase delay lead to young adults being at high risk of circadian misalignment. We have previously established a self-rating of biological rhythm disorder for adolescents (SBRDA). However, we did not externally validate the SBRDA against objective measures of biological rhythms such as dim light melatonin onset (DLMO)-the gold standard of the endogenous circadian phase. The purpose of this study was to verify the effectiveness of SBRDA in identifying individuals with biological rhythm disorders. Our participants were 42 (47.2%) boys and 47 (52.8%) girls with an average age of 18.5 ± 1.2 years. Saliva samples were collected from 4 h before bed time to 2 h after sleep every 60 min in a dim-light (<50 lx) laboratory environment. Biological rhythm parameters were assessed using questionnaires, including SBRDA, MEQ, and MCTQ. The mean DLMO time (h) was 22.2 ± 1.9. The DLMO correlated significantly with the SBRDA score (r = 0.33, p < 0.001), MEQ score (r = -0.24, p < 0.05), and MSFsc (r = 0.26, p < 0.05). ROC curve analysis showed that SBRDA was of diagnostic value for biological rhythm disorder (p < 0.05). Our observations demonstrate that SBRDA, which is consistent with MEQ and MCTQ, can be used to reflect endogenous circadian rhythm disorders in young adults. Exposure to dim light may activate melatonin secretion and lead to an earlier peak in young adults with biological rhythm disorder.

Age-related and individual features of the HPA axis stress responsiveness under constant light in nonhuman primates.

The hypothalamic-pituitary-adrenal (HPA) axis is a key adaptive neuroendocrine system, dysfunction of which plays an important role in the increasing incidence of stress-dependent age-related pathology. Among the environmental factors effecting increase age-related diseases, great importance is given to disturbances of the light-dark schedule, particularly with increased illumination at night. While disruption of the light-dark schedule has long been recognized as a powerful behavioral stressor, little is known regarding stress reactivity of the HPA under constant light (CL) conditions, especially with aging and depending on the features of stress behavior. The purpose of this investigation was to study the age-related and individual features of the HPA axis response to acute stress exposure (ASE) under chronic CL in nonhuman primates that are known to differ in behavioral responsiveness to stress. Young and old female rhesus monkeys (with control standard behavior or anxiety and depression-like behavior) were exposed to CL (24h light/day, 330-400 lux for 4 to 8 weeks). Control young and old monkeys were exposed to standard lighting (SL) with natural light during the day and darkness at night. All animals were subjected to ASE (restriction of mobility for 2 hours), functional tests with corticotrophin-releasing hormone and arginine-vasopressin, and study of circadian rhythms of cortisol and pineal melatonin secretion. For the first time an inhibitory effect of CL on the reaction of the adrenal cortex to ASE was revealed in all individuals, regardless of age and preexisting behavior stress reactivity, the mechanisms of which were age-dependent: due to inhibition of the pituitary ACTH secretion in young animals and mainly not affecting the ACTH secretion in old individuals. There were no significant changes in melatonin secretion both in young and old animals. The observed CL inhibition of adrenal cortical reactivity to ASE may be useful to correct increased vulnerability to ASE observed in individuals with preexisting anxiety and depression-like stress behaviors. On the other hand, the CL induced decrease in adrenal stress reactivity of behaviorally normal animals suggests a potential risk of reducing the adaptive capacity of the organism under conditions of continuous light exposure.