Melatonin Rhythm Research Articles

Disruption of the circadian rhythm of melatonin: A biomarker of critical illness severity

Circadian dysrhythmias occur commonly in critically ill patients reflecting variable effects of underlying illness, ICU environment, and treatments. We retrospectively analyzed the relationship between clinical outcomes and 24-h urinary 6-sulfatoxymelatonin (aMT6s) excretion profiles in 37 critically ill patients with shock and/or respiratory failure. Nonlinear regression was used to fit a 24-h cosine curve to each patient's aMT6s profile, with rhythmicity determined by the zero-amplitude test. From these curves we determined acrophase, amplitude, phase, and night/day ratio. After assessing unadjusted relationships, we identified the optimal multivariate models for hospital survival and for discharge to home (vs. death or transfer to another facility). Normalized aMT6s rhythm amplitude was greater (p = 0.005) in patients discharged home than in those who were not, while both groups exhibited a phase delay. Patients with rhythmic aMT6s excretion were more likely to survive (OR 5.25) and be discharged home (OR 8.89; p < 0.05 for both) than patients with arrhythmic profiles, associations that persisted in multivariate modelling. In critically ill patients with shock and/or respiratory failure, arrhythmic and/or low amplitude 24-h aMT6s rhythms were associated with worse clinical outcomes, suggesting a role for the melatonin-based rhythm as a novel biomarker of critical illness severity.

Sleep-light interventions that shift melatonin rhythms earlier improve perimenopausal and postmenopausal depression: preliminary findings.

Testing the hypothesis that a sleep-light intervention, which phase-advances melatonin rhythms, will improve perimenopausal-postmenopausal (P-M; by follicle-stimulating hormone) depression. In at-home environments, we compared two contrasting interventions: (1) an active phase-advance intervention: one night of advanced/restricted sleep from 9 pm to 1 am , followed by 8 weeks of morning bright white light for 60 min/d within 30 minutes of awakening, and (2) a control phase-delay intervention: one night of delayed/restricted sleep (sleep from 3 to 7 am ) followed by 8 weeks of evening bright white light for 60 min/d within 90 minutes of bedtime. We tested 17 P-M participants, 9 normal controls and 8 depressed participants (DPs) (by Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] criteria). Clinicians assessed mood by structured interviews and subjective mood ratings. Participants wore actigraphs to measure sleep and activity and collected overnight urine samples for the melatonin metabolite, 6-sulfatoxymelatonin (6-SMT), before, during, and after interventions. Baseline depressed mood correlated with delayed 6-SMT offset time (cessation of melatonin metabolite [6-SMT] secretion) ( r = +0.733, P = 0.038). After phase-advance intervention versus phase-delay intervention, 6-SMT offset (start of melatonin and 6-SMT decrease) was significantly advanced in DPs (mean ± SD, 2 h 15 min ± 12 min; P = 0.042); advance in 6-SMT acrophase (time of maximum melatonin and 6-SMT secretion) correlated positively with mood improvement ( r = +0.978, P = 0.001). Mood improved (+70%, P = 0.007) by both 2 and 8 weeks. These preliminary findings reveal significantly phase-delayed melatonin rhythms in DP versus normal control P-M women. Phase-advancing melatonin rhythms improves mood in association with melatonin advance. Thus, sleep-light interventions may potentially offer safe, rapid, nonpharmaceutical, well-tolerated, affordable home treatments for P-M depression.

Shift and longtime light induces endometrioid adenocarcinoma via activation of PKC-α/Akt pathway in female golden hamster: Involvement of altered Aanat and Bmal1 rhythm.

Female night-workers get exposed to frequent light shifts, hence have altered circadian rhythm and are at high risk of endometrial cancer; the underlying mechanism however is still not clear. We, therefore examined the effect of long light exposure (16L:8D, LD1) and regular shift (8 h) in long nighttime (LD2) on endometrial changes of female golden hamsters. Morphometric analysis, scanning electron microscopy imaging, alcian blue staining, and cytological nuclear atypia of endometrial stromal cells confirmed the incidence of endometrial adenocarcinoma in LD2 exposed hamsters. But, less severe pathomorphological alterations were noted in uterus of LD1 exposed hamsters. Altered Aanat and Bmal1 mRNA, melatonin rhythm, downregulation of important marker gene of adenocarcinoma like Akt, 14-3-3, and PR protein expression and upregulation PKCα, pAkt-S473 and vascular epithelial growth factor (VEGF) were observed in LD2 exposed hamsters suggesting the endometrial adenocarcinoma. Further, our western blot analysis supported the immunohistochemical localization of PR, PKCα, and VEGF in uterine tissues along low progesterone. Overall, our data indicates that light shift and long light exposure potentially induced endometrioid adenocarcinoma via activation of PKC-α/Akt pathway in female hamsters. Therefore, duration of light is essential for female normal uterine function.

Circadian Rhythm Disturbance in Acute Ischemic Stroke Patients and Its Effect on Prognosis

Introduction: Poststroke sleep disturbances are common and can affect stroke outcomes, but the clinical studies mainly focus on breathing-related sleep disorders, while the bidirectional impact of circadian rhythm dysfunction in ischemic stroke remains unknown. This study observed the characteristics of melatonin secretion in acute ischemic stroke patients and evaluated whether melatonin rhythm impacts the prognosis after stroke by assessing the neurological function, cognition, emotion, and quality of life 3 months after stroke. Methods: Acute ischemic stroke patients were selected from the Department of Neurology Inpatients of the Second Hospital affiliated with Soochow University from October 2019 to July 2021. Healthy control subjects were recruited at the same time. Demographic and clinical data were collected, and relevant scale scores (including neurological function, cognition, emotion, and sleep) were assessed within 2 weeks of onset and followed up 3 months later. All participants collected salivary melatonin samples on the 4th day of hospitalization and dim light melatonin onset (DLMO) was calculated according to melatonin concentration. Stroke patients were then divided into three groups based on their DLMO values. Results: A total of 74 stroke patients and 33 control subjects were included in this analysis. Compared with healthy controls, stroke patients exhibited a delayed melatonin rhythm during the acute phase of stroke (21:36 vs. 20:38, p = 0.004). Stroke patients were then divided into three groups, namely normal (n = 36), delayed (n = 28), or advanced DLMO (n = 10), based on their DLMO values. A χ² test showed that there were significant differences in the rate of poor prognosis (p = 0.011) and depression tendency (p = 0.028) among the three groups. A further pairwise comparison revealed that stroke patients with delayed DLMO were more likely to experience poor short-term outcomes than normal DLMO group (p = 0.003). The average melatonin concentration of stroke patients at 5 time points was significantly lower than that of the control group (3.145 vs. 7.065 pg/mL, p < 0.001). Accordingly, we split stroke patients into three groups, namely low melatonin level (n = 14), normal melatonin level (n = 54), or high melatonin level (n = 6). Unfortunately, there were no great differences in the clinical characteristics, cognition, emotion, sleep quality, and short-term outcome among groups. Conclusions: This is a preliminary study, and our results indicate that changes in melatonin secretion phase of stroke patients may have effect on their short-term prognosis.

Maternal melatonin levels and temporal dietary intake: results from MY-CARE cohort study

Chrononutrition emerges as a novel approach to promote circadian alignment and metabolic health by means of time-of-the-day dietary intake. However, the relationship between maternal circadian rhythm and temporal dietary intake during pregnancy remains understudied. This study aimed to determine the change in melatonin levels in pregnant women across gestation and its association with temporal energy and macronutrient intake. This was a prospective cohort involving 70 healthy primigravidas. During the second and third trimesters, pregnant women provided salivary samples collected at 9:00, 15:00, 21:00, and 3:00 h over a 24 h day for melatonin assay. Data on chrononutrition characteristics were collected using a 3-day food record. Parameters derived from melatonin measurements including mean, amplitude, maximal level, area under the curve with respect to increase (AUCI), and area under the curve with respect to ground (AUCG) were computed. A rhythmic melatonin secretion over the day that remained stable across trimesters was observed among the pregnant women. There was no significant elevation in salivary melatonin levels as pregnancy advanced. In the second trimester, higher energy intake during 12:00–15:59 h and 19:00–06:59 h predicted a steeper melatonin AUCI (β=-0.32, p = 0.034) and higher AUCG (β = 0.26, p = 0.042), respectively. Macronutrient intake within 12:00–15:59 h was negatively associated with mean melatonin (Fat: β=-0.28, p = 0.041) and AUCG (Carbohydrate: β=-0.37, p = 0.003; Protein: β=-0.27, p = 0.036; Fat: β=-0.32, p = 0.014). As pregnant women progressed from the second to the third trimester, a flatter AUCI was associated with a reduced carbohydrate intake during 12:00–15:59 h (β=-0.40, p = 0.026). No significant association was detected during the third trimester. Our findings show that higher energy and macronutrient intakes particularly during 12:00–15:59 h and 19:00–06:59 h are associated with the disparities in maternal melatonin levels. Findings suggest the potential of time-based dietary approaches to entrain circadian rhythm in pregnant women.

Circadian rhythm disturbance and delirium in ICU patients: a prospective cohort study

BackgroundPatients treated in the intensive care unit (ICU) may experience a reversal of day and night. The circadian rhythm in ICU patients can be disturbed.MethodsTo explore the relationship between ICU delirium and the circadian rhythms of melatonin, cortisol and sleep. A prospective cohort study was carried out in a surgical ICU of a tertiary teaching hospital. Patients who were conscious during the ICU stay after surgery and were scheduled to stay in the ICU for more than 24 h were enrolled. Serum melatonin and plasma cortisol levels were measured three times a day by drawing arterial blood on the first three days after ICU admission. Daily sleep quality was assessed by the Richard-Campbell Sleep Questionnaire (RCSQ). The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) was performed twice a day to screen for ICU delirium.ResultsA total of 76 patients were included in this study, and 17 patients developed delirium during their ICU stay. Melatonin levels were different at 8:00 (p = 0.048) on day 1, at 3:00 (p = 0.002) and at 8:00 (p = 0.009) on day 2, and at all three time points on day 3 (p = 0.032, 0.014, 0.047) between delirium and non-delirium patients. The plasma cortisol level in the delirium patients was significantly lower than that in the non-delirium patients at 16:00 on day 1 (p = 0.025). The changes in melatonin and cortisol secretion levels exhibited obvious biological rhythmicity in non-delirium patients (p < 0.001 for melatonin, p = 0.026 for cortisol), while no rhythmicity was found in melatonin and cortisol secretion levels in the delirium group (p = 0.064 for melatonin, p = 0.454 for cortisol). There was no significant difference in RCSQ scores in the first three days between the two groups.ConclusionsThe disturbance of the circadian rhythm of melatonin and cortisol secretion was associated with the development of delirium in ICU patients. Clinical staff should pay more attention to the importance of maintaining patients’ normal circadian rhythms in the ICU.Trial registrationThe study was registered with the US National Institutes of Health ClinicalTrials.gov(NCT05342987) (25/04/2022).

Investigating the effects of a blue-blocking software on the daily rhythm of sleep, melatonin, cortisol, positive and negative emotions

ABSTRACT Since the use of light and electronic devices is inevitable, the use of blue light filters (in various light sources, electronic devices or optical devices including intraocular lenses) has been shown to improve sleep quality, especially in later hours of the day and during night time. In this study, we examine the effect of the blue light on sleep and wakefulness rhythms and positive and negative emotions. This randomized clinical trial was conducted with 80 AJA University of Medical Sciences employees who use computers at least 2 h a day. All subjects were employees of the discharge unit of Imam Reza Hospital, which is located next to AJA University. The subjects were divided into two groups of 40 people, blue light filter software intervention and sham treatment. Pittsburgh Sleep Quality Index (PSQI), Positive and Negative Affect Schedule (PANAS), Visual Function Questionnaire (VFQ), Epworth Sleepiness Scale (ESS) and salivary melatonin and cortisol levels were assessed for both groups before and 3 months after the intervention. Data analysis was performed using IBM SPSS statistics for windows, version 21.0 (Armonk, NY: IBM Corporation). P value ≤ 0.05 was considered as statistically significant. The results showed that the Pittsburgh sleep scale after the intervention was significantly lower in the intervention group than in the control group. After the intervention, the VFQ was significantly lower in the intervention group than in the control group (P = 0.018). There was no significant difference in the Epworth Sleepiness Scale (ESS) between the two study groups after the intervention (P = 0.370). There was no significant difference in Positive and Negative Affect Schedule (PANAS) in the two study groups after the intervention (P = 0.140). After the intervention, cortisol levels were significantly higher in the intervention group than in the control group (P = 0.006). Also, the amount of cortisol increased significantly in the intervention group (P = 0.028). The amount of melatonin decreased significantly in the intervention group (P = 0.034). The sleep quality score after the intervention was significantly lower in the intervention group than in the control group. This indicates better sleep quality in the intervention group. The results also show that the level of visual fatigue in the intervention group decreased significantly. However, no significant change was detected regarding positive and negative emotions. After the intervention, cortisol levels were significantly higher in the intervention group than the control group. In addition, cortisol levels increased significantly and melatonin levels decreased significantly in the intervention group during the course of study.

0860 Comparative description of sleep, thyroid-stimulating hormone and calcium metabolism in 5 vitiligo patients under phototherapy

Abstract Introduction Vitiligo is an autoimmune skin disease represented by melanocytes destruction. Clinically, it evolves with spots that are lighter than normal skin color. Periodical evaluation of patients is recommended, including thyroid function. Phototherapy is its gold standard treatment, consisting in specific range of ultraviolet B (UVB) light sections. Sleep may play an immunological role, and should be investigated in vitiligo. The study aimed to compare results of thyroid-stimulating hormone (TSH), parathyroid hormone (PTH), serum calcium and vitamin D 1.25(OH)2D and 25(OH)D; and Pittsburgh Sleep Quality Index (PSQI) scores of vitiligo patients before and after phototherapy period. Methods Five individuals with vitiligo were evaluated at a University Dermatology Service, following ethical guidelines. Blood collection and PSQI application were performed before and after phototherapy. Laboratory elements were those related to calcium metabolism (PTH, calcium and vitamin D) and TSH. Results The sample included 4 female individuals with 21, 46, 65 and 70 years old; and a 57 years old male. Three of them had large skin involvement and 2 had localized vitiligo. After 6 months under phototherapy, patients returned for reassessment. All showed skin lesions improvement. Quantitative increase in TSH, PTH, 1.25(OH)2D and 25(OH)D was observed; serum calcium varied among the sample. Regarding PSQI before phototherapy, all 5 scores were &amp;gt;5 (1 score&amp;gt;10). The PSQI was reapplied only in 3 of the 5 volunteers after phototherapy; 2 scores reduced, and 1 score increased. This results, although from few individuals, alert to the possible role of UVB phototherapy on TSH and calcium metabolism substrates. Vitamin D increase may be associated to improvement of subjective sleep of 2 individuals. It was described that vitamin D in sufficient concentration could be related to better sleep quality. Phototherapy, by acting on clinical improvement of vitiligo, may influence subjective sleep, as reported in PSQI; and it could influence on melatonin and circadian rhythm. Conclusion The interaction between vitiligo/autoimmunity, phototherapy, vitamin D and sleep is complex and may have interrelated pathways. A better understanding of this pathophysiology through larger studies is worthy for benefiting clinical management of vitiligo and associated sleep disorders. Support (if any) AFIP, CAPES and CNPq.

Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment.

Beyond sleep/wake, clock genes regulate the daily rhythms of melatonin production, motor activity, innate immunity, and mitochondrial dynamics, among others. All these rhythms are affected in Parkinson's disease (PD), suggesting that chronodisruption may be an early stage of the disease. The aim of this study was to evaluate the connection between clock genes and these rhythms in PD, and whether melatonin administration reestablished the normal clock function. Parkinsonism was induced with 600 μM MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in 24-120 h post fertilization (hpf) zebrafish embryos and melatonin was administered at a dose of 1 μM. Day-night melatonin rhythm disappeared in MPTP-treated embryos, which showed an advance in the activity phase in parallel with changes in the rhythm of clock genes. An alteration in the fission-to-fusion mitochondrial dynamics was also detected in parkinsonian embryos, increasing the former and leading to apoptosis. Melatonin administration to MPTP-treated embryos fully restored the circadian system, including the rhythms of clock genes, motor activity, melatonin rhythm, and mitochondrial dynamics, and decreasing apoptosis. Because clock-controlled rhythms such as sleep/wake alterations are early events in PD, the data here reported may point to chronodisruption as one initial pathophysiological event of the disease.

Brain washing and neural health: role of age, sleep, and the cerebrospinal fluid melatonin rhythm.

The brain lacks a classic lymphatic drainage system.How it is cleansed of damaged proteins, cellular debris, and molecular by-products has remained a mystery for decades. Recent discoveries have identified ahybrid system that includes cerebrospinal fluid (CSF)-filled perivascular spaces and classic lymph vessels in the dural covering of the brain and spinal cord that functionally cooperate to remove toxic and non-functional trash from the brain. These two components functioning together are referred to as the glymphatic system. We propose that the high levels of melatonin secreted by the pineal gland directly into the CSF play a role in flushing pathological molecules such as amyloid-β peptide (Aβ) from the brain via this network. Melatonin is a sleep-promoting agent, with waste clearance from the CNS being highest especially during slow wave sleep. Melatonin is also a potent and versatile antioxidant that prevents neural accumulation of oxidatively-damaged molecules which contribute to neurological decline. Due to its feedback actions on the suprachiasmatic nucleus, CSF melatonin rhythm functions to maintain optimal circadian rhythmicity, which is also critical for preserving neurocognitive health. Melatonin levels drop dramatically in the frail aged, potentially contributing to neurological failure and dementia. Melatonin supplementation in animal models of Alzheimer's disease (AD) defers Aβ accumulation, enhances its clearance from the CNS, and prolongs animal survival. In AD patients, preliminary data show that melatonin use reduces neurobehavioral signs such as sundowning. Finally, melatonin controls the mitotic activity of neural stem cells in the subventricular zone, suggesting its involvement in neuronal renewal.

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.

Prevalence and risk factors of sub-health and circadian rhythm disorder of cortisol, melatonin, and temperature among Chinese midwives.

This study aimed to explore the influencing factors of sub-health and circadian rhythm disorder among midwives and whether circadian rhythm disorder was associated with sub-health. A multi-center cross-sectional study was conducted among 91 Chinese midwives from six hospitals through cluster sampling. Data were collected by demographic questionnaire, Sub-Health Measurement Scale version 1.0, and circadian rhythm detection. Minnesota single and population mean cosine methods were used to analyze the rhythm of cortisol, melatonin, and temperature. Binary logistic regression, nomograph model, and forest plot were performed to identify variables associated with midwives' sub-health. There were 65 midwives with sub-health and 61, 78, and 48 midwives with non-validation of circadian rhythms of cortisol, melatonin, and temperature among 91 midwives, respectively. Midwives' sub-health was significantly related to age, duration of exercise, weekly working hours, job satisfaction, cortisol rhythm, and melatonin rhythm. Based on these six factors, the nomogram was presented with significant predictive performance for sub-health. Furthermore, cortisol rhythm was significantly associated with physical, mental, and social sub-health, whereas melatonin rhythm was significantly correlated with physical sub-health. Sub-health and circadian rhythm disorder were generally common among midwives. Nurse administrators are supposed to pay attention and take measures to prevent sub-health and circadian rhythm disorder among midwives.

Adult Male Syrian Hamsters (Mesocricetus auratus) Exhibit Daily Oscillations in Their Serum Levels of Melatonin and Leptin As Well As in the Expression of the GnRH, GnIH, and Kisspeptin Genes

The complex neuronal and hormonal interaction between the brain and gonads controls the neuroendocrine reproductive axis. GnRH, GnIH, and kisspeptin are important neuropeptides in this relationship. Although seasonal variations of these neuropeptides have been demonstrated in photoperiodic animals, there is no clear evidence in their daily rhythms. Melatonin and leptin hormones are also two important hormones in reproductive regulation. In our study, the relationship of melatonin and leptin hormones with daily rhythm with GnIH, GnRH, and kisspeptin gene expressions and protein oscillations was examined. Adult male Syrian hamsters were exposed to the long photoperiod and at the end of the 30-day experimental period, blood and tissue samples from each group were collected at 04:00 h, 12:00 h, 20:00 h, and 00:00 h. Daily rhythms of melatonin and leptin hormones were determined by ELISA. Quantitative analysis of GnRH, GnIH, Kisspeptin, and β-actin genes was performed with the corresponding primers in Real-Time PCR. Protein expressions were determined by the Western Blot technique. Serum melatonin and leptin levels showed an inverse rhythmic relationship. Leptin level was found to be low while melatonin was high in the dark. Daily rhythms were observed in GnIH, GnRH, and kisspeptin mRNA expressions and protein oscillations. As a result, our findings could imply that all of the relationships between melatonin, leptin, GnIH, GnRH, and kisspeptin are not reproductive, but rather metabolic in nature.

Chrononutrition is associated with melatonin and cortisol rhythm during pregnancy: Findings from MY-CARE cohort study.

Chrononutrition has been suggested to have an entrainment effect on circadian rhythm which is crucial for metabolic health. Investigating how chrononutrition affects maternal circadian rhythm can shed light on its role during pregnancy. This study aims to determine chrononutrition characteristics of healthy primigravida during pregnancy and its association with melatonin and cortisol rhythm across gestation. A total of 70 healthy primigravidas were recruited from ten randomly selected government maternal and child clinics in Kuala Lumpur, Malaysia. During the second and third trimesters, chrononutrition characteristics including meal timing, frequency, eating window, breakfast skipping, and late-night eating were determined using a 3-day food record. Pregnant women provided salivary samples at five time-points over a 24 h period for melatonin and cortisol assay. Consistently across the second and third trimesters, both melatonin and cortisol showed a rhythmic change over the day. Melatonin levels displayed an increment toward the night whilst cortisol levels declined over the day. Majority observed a shorter eating window (≤12 h) during the second and third trimesters (66 and 55%, respectively). Results showed 23 and 28% skipped breakfast whereas 45 and 37% ate within 2 h pre-bedtime. During the third trimester, a longer eating window was associated with lower melatonin mean (β = -0.40, p = 0.006), peak (β = -0.42, p = 0.006), and AUCG (β = -0.44, p = 0.003). During both trimesters, a lower awakening cortisol level was observed in pregnant women who skipped breakfast (β = -0.33, p = 0.029; β = -0.29, p = 0.044). Only during the second trimester, breakfast-skipping was significantly associated with a greater cortisol amplitude (β = 0.43, p = 0.003). Findings suggest that certain chrononutrition components, particularly eating window and breakfast skipping have a significant influence on maternal melatonin and cortisol rhythm. Dietary intervention targeting these characteristics may be useful in maintaining maternal circadian rhythm.

Leptin and melatonin rhythms in Syrian hamsters during inflammation

Leptin and melatonin rhythms in Syrian hamsters during inflammation

Inhibiting nighttime melatonin and boosting cortisol increase patrolling monocytes, phagocytosis, and myelination in a murine model of multiple sclerosis

Conflicting results on melatonin synthesis in multiple sclerosis (MS) have been reported due to variabilities in patient lifestyles, which are not considered when supplementing melatonin. Since melatonin acts through its receptors, we identified melatonin receptors in oligodendrocytes (OLs) in the corpus callosum, where demyelination occurs; the subventricular zone, where neural stem/progenitor cells (NSPCs) are located; and the choroid plexus, which functions as a blood-cerebrospinal fluid barrier. Moreover, using chimeric mice, resident macrophages were found to express melatonin receptors, whereas bone marrow-derived macrophages lost this expression in the demyelinated brain. Next, we showed that cuprizone-fed mice, which is an MS model, tended to have increased melatonin levels. While we used different approaches to alter the circadian rhythm of melatonin and cortisol, only the constant light approach increased NSPC proliferation and differentiation to oligodendrocyte precursor cells (OPCs), OPCs maturation to OLs and recruitment to the site of demyelination, the number of patrolling monocytes, and phagocytosis. In contrast, constant darkness and exogenous melatonin exacerbated these events and amplified monocyte infiltration. Therefore, melatonin should not be considered a universal remedy, as is currently claimed. Our data emphasize the importance of monitoring melatonin/cortisol oscillations in each MS patient by considering diet and lifestyle to avoid melatonin overdose.

Critically-timed sleep+light interventions differentially improve mood in pregnancy vs. postpartum depression by shifting melatonin rhythms

BackgroundTesting the hypothesis that combined wake + light therapy improves mood in pregnant vs. postpartum depressed participants (DP) by differentially altering melatonin and sleep timing. MethodsInitially 89 women, 37 pregnant (21 normal controls-NC; 16 DP) and 52 postpartum (27 NCs; 25 DP), were randomized to a parallel trial of a phase-delay intervention (PDI): 1-night of early-night wake therapy (sleep 3-7 am) + 6-weeks of evening bright white light (Litebook Advantage) for 60 min starting 90 min before bedtime, vs. a Phase-advance intervention (PAI): 1-night of late-night wake therapy (sleep 9 pm-1 am) + 6-weeks of morning bright white light for 60 min within 30 min of wake time. Blinded clinicians assessed mood weekly by structured interview, and participants completed subjective ratings, a Morningness-Eveningness questionnaire, actigraphy, and collected 2 overnight urine samples for 6-sulphatoxy melatonin (6-SMT). ResultsIn pregnant DP, mood improved more after the PDI vs. PAI (p = .016), whereas in postpartum DP, mood improved more after the PAI vs. PDI (p = .019). After wake therapy, 2 weeks of light treatment was as efficacious as 6 weeks (p > .05). In postpartum DP, PAI phase-advanced 6-SMT offset and acrophase (p < .05), which correlated positively with mood improvement magnitude (p = .003). LimitationsSmall N. ConclusionsMood improved more after 2 weeks of the PDI in pregnant DP, but more after 2 weeks of PAI in postpartum DP in which improvement magnitude correlated with 6-SMT phase-advance. Thus, critically-timed Sleep + Light Interventions provide safe, efficacious, rapid-acting, well-tolerated, at-home, non-pharmaceutical treatments for peripartum DP.

Artificial Dim Light at Night during Pregnancy Can Affect Hormonal and Metabolic Rhythms in Rat Offspring.

Artificial light at night (ALAN) is considered an environmental risk factor that can interfere with the circadian control of the endocrine system and metabolism. We studied the impact of ALAN during pregnancy on the hormonal and biochemical parameters in rat pups at postnatal (P) days P3, P10, and P20. Control dams (CTRL) were kept in a standard light-dark regime, and ALAN dams were exposed to dim ALAN (<2 lx) during the whole pregnancy. A plasma melatonin rhythm was found in all CTRL groups, whereas in ALAN pups, melatonin was not rhythmic at P3, and its amplitude was lowered at P10; no differences were found between groups at P20. Plasma corticosterone was rhythmic at P20 in both groups, with decreased mesor in ALAN pups. Plasma thyroid hormones exhibited an inconsistent developmental pattern, and vasopressin levels were suppressed at the beginning of the dark phase at P20 in ALAN compared to CTRL. Glucose and cholesterol showed significant daily rhythms in CTRL but not in ALAN offspring at P3. Exposure to ALAN during pregnancy disturbed the development of daily rhythms in measured hormones and metabolites, suggesting that ALAN during pregnancy can act as an endocrine disruptor that can interfere with the normal development of the progeny.

Circadian Rhythm Changes in Healthy Aging and Mild Cognitive Impairment.

Disruptions in circadian rhythms can occur in healthy aging; however, these changes are more severe and pervasive in individuals with age-related and neurodegenerative diseases, such as dementia. Circadian rhythm alterations are also present in preclinical stages of dementia, for example, in patients with mild cognitive impairments (MCI); thus, providing a unique window of opportunity for early intervention in neurodegenerative disorders. Nonetheless, there is a lack of studies examining the association between relevant changes in circadian rhythms and their relationship with cognitive dysfunctions in MCI individuals. In this review, circadian system alterations occurring in MCI patients are examined compared to healthy aging individuals while also considering their association with MCI neurocognitive alterations. The main findings are that abnormal circadian changes in rest-activity, core body temperature, melatonin, and cortisol rhythms appear in the MCI stage and that these circadian rhythm disruptions are associated with some of the neurocognitive deficits observed in MCI patients. In addition, preliminary evidence indicates that interventions aimed at restoring regular circadian rhythms may prevent or halt the progress of neurodegenerative diseases and mitigate their related cognitive impairments. Future longitudinal studies with repeated follow-up assessments are needed to establish the translational potential of these findings in clinical practice.

Impact of Evening Light Exposures with Different Solid Angles on Circadian Melatonin Rhythms, Alertness, and Visual Comfort in an Automotive Setting.

Future automotive interior lighting might have the potential to go beyond decorative purposes by influencing alertness, circadian physiology, and sleep. As the available space in the interior of an automobile for lighting applications is limited, understanding the impact of various luminous surface sizes on non-image-forming effects is fundamental in this field. In a laboratory study using a within-subject design, 18 participants were exposed to two bright light conditions with different solid angles and one dim light condition in a balanced, randomized order during the course of the evening. Our results demonstrate that both light conditions significantly increased subjective alertness and reduced salivary melatonin concentration but not cognitive performance compared to dim light. The solid angle of light exposure at constant corneal illuminance only affected visual comfort. While subjective alertness can be increased and melatonin can be attenuated with rather small luminaires, larger solid angles should be considered if visual comfort is a priority.