Circadian Rhythm Of Melatonin Research Articles

Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic REM sleep behavior disorder

ObjectiveTo evaluate changes in the expression of clock genes and melatonin levels in patients with idiopathic REM sleep behavior disorder (RBD) as a potential early stage of synucleinopathies. MethodsWe assessed the rhythmicity of circadian clock genes using real time-quantitative polymerase chain reaction and 24-h blood melatonin profiles using radio-immunoassay in 10 RBD patients and nine age-matched controls. ResultsThe RBD patients did not show circadian rhythmicity for clock genes Per2, Bmal1, and Nr1d1 but the rhythmicity of Per 1 remained, and the amplitude of Per3 was diminished. The 24-h melatonin rhythm did not differ between RBD patients and healthy control subjects. Melatonin profile in RBD patients was delayed by 2 h compared to controls, the habitual sleep phases were phase delayed by about 1 h, however no phase shift occurred in any of the clock genes studied. The control group had stable acrophases of melatonin rhythms of approximately 5 h whereas the RBD patients had a more dispersed range over 11 h. ConclusionsOur results suggest that RBD could be associated with altered expression of clock genes and delayed melatonin secretion. Thus, we argue that circadian system dysregulation could play a role in RBD.

Association of 3111T/C Polymorphism of the Clock Gene with Circadian Rhythm of Melatonin in Menopausal Women with Insomnia

We carried out a comparative analysis of circadian rhythms of melatonin secretion in Caucasian menopausal women with and without insomnia depending on the 3111T/C polymorphism of the Clock gene. Melatonin levels was measured in the saliva 4 times a day (06.00-07.00, 12.00-13.00, 18.00-19.00, and 23.00-00.00 h). Carriers of the TT genotype with insomnia demonstrated significantly higher level of melatonin in the early morning hours compared to the carriers of the minor allele C (12.60±7.58 and 8.98±8.62 pg/ml, respectively, p=0.023). In the control group, no statistically significant differences were revealed. The carriers of the TT genotype with sleep disorders have higher morning melatonin level compared to control group women (12.60±7.58 and 5.48±4.74 pg/ml, respectively, p=0.005) and low nocturnal melatonin level (6.42±4.97 and 12.52±10.40 pg/ml, respectively, p=0.039).

Circadian rhythms of melatonin and behaviour in juvenile sheep in field conditions: Effects of photoperiod, environment and weaning.

Entrainment of circadian rhythms (CR) to the light dark cycle has been well described under controlled, experimental conditions. However, studies in rodents have reported that rhythms in the laboratory are not always reproduced under field conditions. The aim of this study was to characterise the CR of sheep maintained under conditions of standard UK farm animal husbandry and to investigate the effects of environmental challenges presented by season, weaning and changes in housing on CR. Male sheep (n = 9) were kept at pasture, or group housed in barns, under natural photoperiod for one year. CR in locomotor activity were monitored using accelerometry, and 24 h patterns in plasma cortisol and melatonin were measured every 4 h by ELISA. CR was measured before and after weaning, in summer and winter, and at pasture and by barn housing. Cosinor analysis revealed high amplitude, diurnal rhythms in locomotor activity that were disrupted by weaning and by barn housing. Rhythms in winter showed an interrupted night time activity pattern, but only when the sheep were kept at pasture. Cortisol and melatonin secretion followed typical circadian patterns in winter and summer. The CR of the sheep under the field conditions of this study were strikingly robust under basal conditions, but easily disrupted by environmental challenges. Interrupted patterns of activity during the long nights of wintertime, not previously reported for sheep kept in experimental conditions were recorded. Based on these findings, we propose that animals require exposure to more complex environments than the laboratory in order to exhibit their true circadian phenotype.

Agomelatine treatment corrects symptoms of depression and anxiety by restoring the disrupted melatonin circadian rhythms of rats exposed to chronic constant light

Desynchronization of circadian rhythms is a hallmark of depression. The antidepressant agomelatine, which is an MT1/MT2 melatonin receptor agonist/5-HT2C serotonin receptor antagonist has advantages compared to the selective serotonin reuptake inhibitors as a circadian phase-shifting agent. The present study was designed to explore whether agomelatine is able to have an antidepressant effect on rats exposed to chronic constant light (CCL) for 6 weeks. Focus is also placed on whether this activity affects diurnal rhythms of depressive-like symptoms and is associated with restoration of impaired circadian rhythms in plasma melatonin and corticosterone. We report that CCL induced a depressive-like symptoms associated with decreased grooming in the splash test during the subjective light/inactive phase. Anhedonia-like deficit in the saccharine preference test and increased immobility in the forced swimming test were both detected during the subjective dark/active phase. The disturbed emotional fluctuations due to CCL were corrected by agomelatine treatment (40 mg/kg, i.p. for 3 weeks). Agomelatine also restored novelty-induced hypophagia, which reflects an anxiety state, during the subjective Light and Dark phase, respectively, in rats exposed to CCL. Parallel to the observed positive influence on behavior, this melatonin analogue restored impaired circadian patterns of plasma melatonin but not that of corticosterone. These findings demonstrated the antidepressant-like effect of agomelatine in rats exposed to CCL possibly exerted via correction of melatonin rhythms and are suggestive of the therapeutic potential of this drug in a subpopulation of people characterized by a melatonin deficit.

Circadian rhythms of melatonin in haemolymph and optic lobes of Chinese mitten crab (Eriocheir sinensis) and Chinese grass shrimp (Palaemonetes sinensis)

This study is the first to examine the circadian rhythms of melatonin in Eriocheir sinensis and Palaemonetes sinensis, two economically important crustaceans. We collected haemolymph and optic lobes from both species every 4 h over a whole day cycle. Melatonin content was measured with high-performance liquid chromatography. E. sinensis haemolymph exhibited significant (p < 0.05) peaks in melatonin at 16:00 (0.180 ± 0.020 μg·mL−1) and 24:00 (0.244 ± 0.055 μg·mL−1), while eyestalks had significant peaks at 16:00 (72.377 ± 18.100 μg·eyestalk−1) and 24:00 (98.756 ± 30.271 μg·eyestalk−1). In P. sinensis, melatonin peaked significantly only at 16:00 in optic lobes (12.493 ± 1.475 μg·eyestalk−1) (p < 0.05); no significant peaks were present in haemolymph. Thus, both E. sinensis and P. sinensis exhibit species-specific melatonin rhythms. Time of day should therefore be considered when examining the physiological status of both crustaceans, given the potential influence of fluctuating daily melatonin concentrations.

The role of melatonin and cortisol circadian rhythms in the pathogenesis of infantile colic

Despite the high prevalence of infantile colic, the pathogenesis remains incompletely understood. Cortisol and melatonin hormones affect gastrointestinal system development in several ways, and interestingly, both cortisol and melatonin's circadian rhythms begin around the 3rd month in which infantile colic symptoms start to decrease. We hypothesized that infantile colic might associate with desynchronization of normal circadian rhythms of these hormones. In this study, we aimed to investigate the role of melatonin and cortisol in the pathogenesis of infantile colic. Patients who were diagnosed as infantile colic according to Wessel's "rule of three" were enrolled in the colic group. We measured the saliva melatonin and cortisol levels of colic group and control group infants. In both groups, the saliva samples were taken in mornings and at evenings, at the time of diagnosis and 6th month. Fifty-five infants finished the study. Melatonin circadian rhythm developed earlier in the control group than the infantile colic group in our study. We found no significant difference between the daily mean cortisol levels. However, infants with colic had flatter daily cortisol slope than controls which pointed out the probability that they had a less clearly defined cortisol rhythm than infants without colic. We found an association between melatonin levels and infantile colic. However, more research is needed to fully understand the role of hypothalamic-pituitary-adrenalaxis and hormone's role on infantile colic physiopathology.

How to Monitor the Neuroimmune Biological Response in Patients Affected by Immune Alteration-Related Systemic Diseases.

The clinical management of patients affected by systemic diseases, including cancer and autoimmune diseases, is generally founded on the evaluation of the only markers related to the single disease rather than the biological immuno-inflammatory response of patients, despite the fundamental role of cytokine network in the pathogenesis of cancer and autoimmunity is well known. Cancer progression has appeared to be associated with a progressive decline in the blood levels of the main antitumor cytokines, including IL-2 and IL-12, in association with an increase in those of inflammatory cytokines, including IL-6, TNF-alpha, and IL-1-beta, and immunosuppressive cytokines, namely TGF-beta and IL-10. On the other hand, the severity of the autoimmune diseases has been proven to be greater in the presence of high blood levels of IL-17, TNF-alpha, IL-6, IL-1-beta, IFN-gamma, and IL-18, in association with low levels of TGF-beta and IL-10. However, because of excessive cost and complexity of analyzing the data regarding the secretion of the single cytokines, the relation between lymphocyte-induced immune activation and monocyte-macrophage-mediated immunosuppression has been recently proven to be expressed by the simple lymphocyte-to-monocyte ratio (LMR). The evidence of low LMR values has appeared to correlate with a poor prognosis in cancer and with a disease control in the autoimmune diseases. Moreover, since the in vivo immunoinflammatory response is physiologically under a neuroendocrine modulation, for the evaluation of patient biological response it would be necessary to investigate the function of at least the two main neuroendocrine structures involved in the neuroendocrine modulation of the immune responses, consisting of the hypothalamic-pituitary-adrenal axis and the pineal gland, since the lack of physiological circadian rhythm of cortisol and pineal hormone melatonin has appeared to be associated with a worse prognosis in the human systemic diseases.

Deciphering the Function of the Blunt Circadian Rhythm of Melatonin in the Newborn Lamb: Impact on Adrenal and Heart.

Neonatal lambs, as with human and other neonates, have low arrhythmic endogenous levels of melatonin for several weeks until they start their own pineal rhythm of melatonin production at approximately 2 weeks of life. During pregnancy, daily rhythmic transfer of maternal melatonin to the fetus has important physiological roles in sheep, nonhuman primates, and rats. This melatonin rhythm provides a circadian signal and also participates in adjusting the physiology of several organs in preparation for extrauterine life. We propose that the ensuing absence of a melatonin rhythm plays a role in neonatal adaptation. To test this hypothesis, we studied the effects of imposing a high-amplitude melatonin rhythm in the newborn lamb on (1) clock time-related changes in cortisol and plasma variables and (2) clock time-related changes of gene expression of clock genes and selected functional genes in the adrenal gland and heart. We treated newborn lambs with a daily oral dose of melatonin (0.25 mg/kg) from birth to 5 days of age, recreating a high-amplitude melatonin rhythm. This treatment suppressed clock time-related changes of plasma adrenocorticotropic hormone, cortisol, clock gene expression, and functional genes in the newborn adrenal gland. In the heart, it decreased heart/body weight ratio, increased expression of Anp and Bnp, and resulted in different heart gene expression from control newborns. The interference of this postnatal melatonin treatment with the normal postnatal pattern of adrenocortical function and heart development support a physiological role for the window of flat postnatal melatonin levels during the neonatal transition.

Sleep-wake profiles and circadian rhythms of core temperature and melatonin in young people with affective disorders

While disturbances of the sleep-wake cycle are common in people with affective disorders, the characteristics of these disturbances differ greatly between individuals. This heterogeneity is likely to reflect multiple underlying pathophysiologies, with different perturbations in circadian systems contributing to the variation in sleep-wake cycle disturbances. Such disturbances may be particularly relevant in adolescents and young adults with affective disorders as circadian rhythms undergo considerable change during this key developmental period. This study aimed to identify profiles of sleep-wake disturbance in young people with affective disorders and investigate associations with biological circadian rhythms. Fifty young people with affective disorders and 19 control participants (aged 16–31 years) underwent actigraphy monitoring for approximately two weeks to derive sleep-wake cycle parameters, and completed an in-laboratory assessment including evening dim-light saliva collection for melatonin assay and overnight continuous core body temperature measurement. Cluster analysis based on sleep-wake cycle parameters identified three distinct patient groups, characterised by ‘delayed sleep-wake’, ‘disrupted sleep’, and ‘long sleep’ respectively. The ‘delayed sleep-wake’ group had both delayed melatonin onset and core temperature nadir; whereas the other two cluster groups did not differ from controls on these circadian markers. The three groups did not differ on clinical characteristics. These results provide evidence that only some types of sleep-wake disturbance in young people with affective disorders are associated with fundamental circadian perturbations. Consequently, interventions targeting endogenous circadian rhythms to promote a phase shift may be particularly relevant in youth with affective disorders presenting with delayed sleep-wake cycles.

Skin Temperature Rhythms in Humans Respond to Changes in the Timing of Sleep and Light.

Body temperature is known to vary with circadian phase and to be influenced by factors that can mask its circadian expression. We wanted to test whether skin temperature rhythms were sensitive to an abrupt shift of the sleep schedule and to the resetting effects of light. Nineteen healthy subjects spent 6 days in time isolation and underwent a simulated night-shift procedure. They were assigned to either a control group ( n = 10) or bright light group ( n = 9) and measurements were taken under a baseline day-oriented schedule and during the 4th cycle of a night-oriented schedule. In the bright light group, participants were exposed to a 3-cycle 8-h exposure of ~6,500 lux at night, while the control group remained in dim light conditions (~3 lux). Skin temperature was recorded in 10 and 4 participants from the control and bright light groups, respectively. We found significant circadian rhythms of plasma melatonin, core body temperature (CBT), and skin temperature at baseline for both groups ( p < 0.001 for all). Rhythms of melatonin, CBT, and skin temperature following night shifts were significantly phase delayed by about 7 to 9 h ( p < 0.05) in response to bright light at night, whereas there was no shift in the control group. In addition, we found that at bedtime melatonin does not consistently increase before the increase in distal skin temperature and subsequent decrease in CBT, in contrast to what has been previously reported. The present study shows that, in constant posture conditions, skin temperature rhythms have an evoked component sensitive to abrupt changes in the timing of sleep. They also comprise an endogenous component that is sensitive to the resetting effects of bright light exposure. These results have applications for the determination of circadian phase, as skin temperature is less intrusive than rectal temperature recordings.

The importance of hormonal circadian rhythms in daily feeding patterns: An illustration with simulated pigs

The interaction between hormonal circadian rhythms and feeding behaviour is not well understood. This study aimed to deepen our understanding of mechanisms underlying circadian feeding behaviour in animals, using pigs, Sus scrofa, as a case study. Pigs show an alternans feeding pattern, that is, a small peak of feed intake at the beginning of the day and a larger peak at the end of the day. We simulated the feeding behaviour of pigs over a 24h period. The simulation model contained mechanisms that regulate feeding behaviour of animals, including: processing of feed in the gastrointestinal tract, fluctuation in energy balance, circadian rhythms of melatonin and cortisol and motivational decision-making. From the interactions between these various processes, feeding patterns (e.g. feed intake, meal frequency, feeding rate) emerge. These feeding patterns, as well as patterns for the underlying mechanisms (e.g. energy expenditure), fitted empirical data well, indicating that our model contains relevant mechanisms. The circadian rhythms of cortisol and melatonin explained the alternans pattern of feeding in pigs. Additionally, the timing and amplitude of cortisol peaks affected the diurnal and nocturnal peaks in feed intake. Furthermore, our results suggest that circadian rhythms of other hormones, such as leptin and ghrelin, are less important in circadian regulation of feeding behaviour than previously thought. These results are relevant to animal species with a metabolic and endocrine system similar to that of pigs, such as humans. Moreover, the modelling approach to understand feeding behaviour can be applied to other animal species.

24 hrs chronomics of BP/HR in terms of double amplitude, acrophase, hyperbaric index and its relation with circadian rhythm of 6-sulfatoxy melatonin in night shift nursing professionals: A Case-control study

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

Melatonin Pharmacological Blood Levels Increase Total Antioxidant Capacity in Critically Ill Patients.

In this study, the aim was to test the biochemical effects of melatonin supplementation in Intensive Care Unit (ICU) patients, since their blood levels are decreased. Sixty-four patients were enrolled in the study. From the evening of the 3rd ICU day, patients were randomized to receive oral melatonin (3 mg, group M) or placebo (group P) twice daily, at 20:00 and 24:00, until discharged. Blood was taken (at 00:00 and 14:00), on the 3rd ICU day to assess basal nocturnal melatonin values, and then during the treatment period on the 4th and 8th ICU days. Melatonin, total antioxidant capacity, and oxidative stress were evaluated in serum. Melatonin circadian rhythm before treatment was similar in the two groups, with a partial preservation of the cycle. Four hours from the 1st administration (4th ICU day, 00:00), melatonin levels increased to 2514 (982.3; 7148) pg·mL−1 in group M vs. 20.3 (14.7; 62.3) pg·mL−1 in group P (p < 0.001). After five treatment days (8th ICU day), melatonin absorption showed a repetitive trend in group M, while in group P nocturnal secretion (00:00) was impaired: 20 (11.5; 34.5) pg·mL−1 vs. 33.8 (25.0; 62.2) on the 3rd day (p = 0.029). Immediately from the beginning of treatment, the total antioxidant capacity was significantly higher in melatonin treated subjects at 00:00; a significant correlation was found between total antioxidant capacity and blood melatonin values (ρ = 0.328; p < 0.001). The proposed enteral administration protocol was adequate, even in the early phase, to enhance melatonin blood levels and to protect the patients from oxidative stress. The antioxidant effect of melatonin could play a meaningful role in the care and well-being of these patients.

Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics.

Melatonin has been speculated to be mainly synthesized by mitochondria. This speculation is supported by the recent discovery that aralkylamine N-acetyltransferase/serotonin N-acetyltransferase (AANAT/SNAT) is localized in mitochondria of oocytes and the isolated mitochondria generate melatonin. We have also speculated that melatonin is a mitochondria-targeted antioxidant. It accumulates in mitochondria with high concentration against a concentration gradient. This is probably achieved by an active transportation via mitochondrial melatonin transporter(s). Melatonin protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting the mitochondrial permeability transition pore (MPTP), and activating uncoupling proteins (UCPs). Thus, melatonin maintains the optimal mitochondrial membrane potential and preserves mitochondrial functions. In addition, mitochondrial biogenesis and dynamics is also regulated by melatonin. In most cases, melatonin reduces mitochondrial fission and elevates their fusion. Mitochondrial dynamics exhibit an oscillatory pattern which matches the melatonin circadian secretory rhythm in pinealeocytes and probably in other cells. Recently, melatonin has been found to promote mitophagy and improve homeostasis of mitochondria.

Circadian Melatonin Rhythm Following Traumatic Brain Injury

Background: Sleep-wake disturbances are highly prevalent following traumatic brain injury (TBI), impeding rehabilitaion and quality of life. However, the mechanisms underlying these sleep disturnbances are unclear, and efficacious treatments are lacking. To investigate possible mechanisms underlying sleep disturbance in TBI, we examined characteristics of the circadian rhythm of melatonin, a hormone involved in sleep-wake regulation. We compared TBI patients reporting sleep disturbance with age- and gender-matched healthy volunteers. Methods: We conducted an overnight observational study with salivary melatonin samples collected hourly in 9 patients with severe TBI and 9 controls. Salivary dim light melatonin onset (DLMO) as well as melatonin synthesis onset (SynOn) and offset (SynOff) were used to determine circadian timing. Total overnight salivary melatonin production was calculated as the area under the curve from melatonin synthesis onset to offset. Results: Compared with healthy individuals, TBI patients showed 42% less melatonin production overnight (d = 0.87; P = .034). The timing of DLMO was delayed by approximately 1.5 hours in patients with TBI compared with controls (d = 1.23; P = .003). Conclusions: In patients with TBI, melatonin production was attenuated overnight, and the timing of melatonin secretion was delayed. We suggest that disruption to the circadian regulation of melatonin synthesis is a feature of severe TBI, possibly contributing to the sleep difficulties that are commonly reported in this population.

Personality differences in patients with delayed sleep–wake phase disorder and non-24-h sleep–wake rhythm disorder relative to healthy sleepers

Objective/BackgroundDelayed sleep–wake phase disorder (DSWPD) is associated with a delayed timing of circadian rhythms, and this delay is suggested to be the basis of the disorder. However, this has been questioned due to frequent relapses following treatment based on this aetiology. Recent studies have emerged suggesting personality factors may contribute to sleep patterns in DSWPD. The aim of this study was to further investigate circadian and personality factors in DSWPD patients as well as patients with non-24-h sleep–wake rhythm disorder (N24SWD) relative to control sleepers. Patients/MethodsThis sample consisted of 16 DSWPD (age = 21.1 ± 2.8, 10 m, 7 f), and three N24SWD patients (age = 24.0 ± 4.4, 2 m, 1 f). Controls were seven males and seven females (age = 23.4 ± 5.9). Before starting an 80-h modified constant routine, eligible participants’ sleep patterns were monitored for a week and they completed a personality questionnaire (NEO PI–R). An ultradian routine with alternating 20-min sleep opportunities and 40 min of enforced wakefulness was used to measure the timing of endogenous circadian temperature and melatonin rhythms. ResultsAs compared with controls, DSWPD patients reported higher neuroticism, significantly lower extraversion, conscientiousness and agreeableness. Similarly, N24SWD patients’ patterns of personality traits were similar to that of DSWPD. Conscientiousness, in particular, was associated with phase timings of circadian rhythms as well as sleep measures and lifestyle factors within the DSWPD group. ConclusionsThese findings suggest that circadian rhythm sleep–wake disorders (CRSWDs) may not only stem from circadian abnormalities but personality factors may also drive lifestyle choices, including sleep timing.

Basing Turkey Lighting Programs on Broiler Research: A Good Idea? A Comparison of 18 Daylength Effects on Broiler and Turkey Welfare.

Simple SummaryAltering daylength in a poultry management program is a simple tool that can have immense impacts on productivity and bird welfare. It is not uncommon for lighting data derived from broiler research to be extrapolated to turkey production. This review of two studies (one with broilers and the second with turkeys), completed in the same research facility using the same lighting programs, shows evidence that some, but not all responses to graded daylengths are similar between these two species. It defines that daylength choices for turkeys should be based on research conducted with turkeys.Daylength used as a management tool has powerful implications on the welfare of both broilers and turkeys. Near-constant light results in many detrimental impacts, including lack of behavioural rhythms and circadian melatonin rhythms. Both are suggestive that sleep fragmentation could result in birds reared on long photoperiods, which can lead to the same negative health and physiological responses as total sleep deprivation. An indirect comparison of the welfare implications of graded levels of daylength on broilers and turkeys clearly indicate that long daylengths depress welfare by increasing mortality, reducing mobility, increasing ocular pathologies and changing behaviour in both species. Furthermore, long daylengths change melatonin secretion patterns and eliminate behavioural and melatonin circadian rhythms, which were measured in broilers in these works. However, feather pecking in turkeys was reduced when birds were exposed to long daylengths. Exactly how much darkness should be included in a management program to maximize welfare will depend on the species, the age of marketing, and in turkeys, bird gender.

Environmental stress of mobile phone EM radiation on locomotor activity and melatonin circadian rhythms of rats

Biological clocks are innate timing mechanisms that regulate many behavioral and physiological parameters in most organisms. In our modern life, heavy use of mobile phones (MPs) exerts a massive stress on organisms because their electromagnetic radiation usually results in varying degrees of damage to their biological systems including the biological rhythms. In the present study, the possible effects of exposure to radiofrequency–electromagnetic radiation (RF–EMR) from MPs on two characteristic circadian rhythms, locomotor activity and melatonin hormone rhythms, were investigated. Rats were exposed to RF–EMR from MPs at 900 MHz frequency (2-h/day for 2 weeks) during nighttime (20:00–22:00 h) followed by another two weeks without exposure for recovery. Locomotor activity rhythms of the control and treated groups (n = 5/group) were daily recorded using running wheels along the experimental period. For evaluating melatonin hormone rhythm, blood samples of control and treated groups (n = 12/group), were collected at the end of exposure and recovery periods, at 6-h time intervals per day (at 4:00, 10:00, 16:00, and 22:00 h). Rats exposed to RF–EMR exhibited phase shifting as well as a significant increased acrophase level in locomotor activity. Meanwhile, a significant decrease in serum melatonin levels with retaining lower amplitude rhythmicity was observed. Ceasing exposure for two weeks did not restore melatonin levels and circadian locomotor activity rhythms. It could be concluded that, under the current conditions, exposure to RF–EMR revealed disturbances in locomotor activity and melatonin level, although they maintained rhythmicity.

Melatonin and cortisol profiles in late midlife and their association with age-related changes in cognition.

Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than in the high-functioning group (−4.6 pg/mL, 95% CI: −7.84, −1.36, P=0.006). The 24-hour mean melatonin concentration (high-functioning group: 4.80±0.70 pg/mL, vs cognitively impaired group: 4.81±0.76 pg/mL; P>0.05) (or the area under the curve, AUC) was not significantly different between the two groups. Cortisol levels were low during the night, and peaked at approximately 8 am. Median cortisol concentrations were similar at all times, as were the 24-hour mean cortisol concentrations and AUC. To the best of our knowledge, ours is the first study to assess circadian measures (ie, melatonin and cortisol) in healthy middle-aged men with different cognitive trajectories in midlife. We found evidence of altered circadian rhythms with a reduced nocturnal melatonin response at 4 am in men with cognitive impairment. The 24-hour concentration and AUC of melatonin and cortisol were similar in the cognitively high-functioning group and in the cognitively impaired.

Analysis of trough and peak of plasma melatonin circadian rhythm in ewes

This study evaluates the pattern of plasma melatonin during the trough and the peak of its daily rhythm. Blood samples from 8 ewes were collected every 3 h for a 48-h period. On the third day, blood samples were collected from 10:00 to 13:00 (trough) and from 20:00 to 23:00 (peak) every 20 min. Our results showed a robust daily rhythm of melatonin in both days of monitoring, with nocturnal acrophase. During the trough, a significant decrease was observed starting from the 10:40 with a progressive decrease about every 40 min. During the peak of the plasma melatonin daily rhythm, an increase was observed starting from the 20:40 with a progressive increase about every 40 min. These data could be taken in consideration to monitor the plasma melatonin variations during the 24 h, and for the administration of melatonin for breeding in ewes.