Plasma Melatonin Rhythm Research Articles

Differential responses to artificial photoperiods of the rising and falling phases of human melatonin rhythm are consistent with a dual oscillator hypothesis.

Circadian rhythms and sleep-wake cycles were measured in volunteers staying singly in temporal isolation unit where they were exposed to artificial short and long light-dark (LD) cycles for 7 days. The long day consisted of 16-h light and 8-h dark (LD 16:8) and the short day consisted of 8-h light and 16-h dark (LD 8:16). During the light period, bright light of approximately 5,000 lux was given from the ceiling and during the dark period there was no illumination. Sleep was monitored by bed sensors, wrist actiwatch, and polysomnography (PSG) on the first and last nights of the schedule. Sleep length was significantly longer under LD 8:16 than under LD 16:8 and the sleep quality estimated by PSG was worse under LD 8:16 than under LD 16:8, which were comparable to natural seasonality in sleep. The circadian rhythm in plasma melatonin was measured in dim light (10 lux) before and after the LD exposures. The nocturnal melatonin secretion (NMS) was significantly longer after LD 8:16 than after LD 16:8 due to differential phase shifts of the rising and falling phases of NMS. After LD 8:16, the falling phase was much advanced than the rising phase, whereas after LD 16:8 the rising phase was much delayed than the falling phase, resulting in the NMS compression. These results indicate that the light sensitivity in terms of phase shifting is different in the two circadian phases, supporting a dual oscillator hypothesis with different phase-response curves for light in the human circadian system.NEW & NOTEWORTHY The present study demonstrated differential light responsiveness of the rising and falling phases of nocturnal melatonin secretion in human subjects exposed to artificial long (LD 16:8) and short days (LD 8:16) and suggested the involvement of different oscillators under these phases. The findings well mimicked the seasonality of the circadian rhythms in nature and consisted with the evening/morning dual oscillator hypothesis proposed originally for nocturnal rodents, providing a new concept for the human circadian system.

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.

Born without night: the consequence of the no-night environment on reproductive performance in diurnal zebra finches.

We investigated the consequence of no-night environment (constant light, LL) on reproductive performance in zebra finches in the parent (P) and subsequent (F1) generation. As a measure of the overall effects on metabolic reproductive health, we monitored daily activity behaviour, recorded song and cheek patch size in males, and measured body size and hormone levels. As compared with controls under 12 h light:12 h darkness (12h:12 h LD), both P and F1 pairs showed a compromised reproductive success, as evidenced by fewer fledglings and fewer viable offspring with longer fledging durations, and increased offspring mortality with three successive clutches under LL. The overall negative effect of the no-night environment was increased in the F1 generation. As compared with P pairs, F1 pairs had more failed nesting and breeding attempts, took longer to initiate reproduction, incubated fewer eggs, produced fewer viable offspring with longer fledging duration, and showed increased offspring mortality. Consistent with negative reproductive effects, P males showed significant changes in the motif duration and other spectral features of song, and both F1 and F2 males copied poorly the song of their parent under LL. Plasma corticosterone and sex hormone (testosterone in males and oestradiol in females) levels were significantly lower under LL. Daily plasma melatonin rhythm persisted but with a reduced amplitude under LL. These results demonstrate the importance of night in reproduction in a continuously breeding diurnal species, and give insight into the possible impact on physiology of animals whose surrounding environment is consistently losing the darkness of night.

Sex-related Changes in Circadian Rhythm of Inflammatory and Oxidative Stress Markers in CKD.

Introduction. Circadian system is deeply involved in renal function. The circadian timing system may be disrupted in chronic kidney disease (CKD) patients. Gender differences in CKD have been reported. This research aimed to investigate the gender differences in the circadian rhythm of inflammatory and oxidant markers of CKD. Methods. Male, intact female, and ovariectomized (OVX) female rats (twenty-four in each group) were randomly assigned to control and CKD groups. The rats were further divided into day (12:00 p.m.) and night (12:00 a.m.) subgroups. Evaluations of each sample were carried out a day after the last day of adenine administration. Results. Final results revealed that the circadian rhythm of plasma melatonin , kidney malondialdehyde (MDA), and transforming growth factor- β (TGF-β) levels in CKD group were the same as the control group. Melatonin and total antioxidant capacity (TAC) levels significantly decreased in the CKD group compared with the control group in day and night subgroups, whereas MDA and TGF-β levels increased. Male group in comparison with the intact female group significantly showed less melatonin and TAC but higher MDA and TGF-β levels which could be due to CKD. Conclusion. Findings of this study represent gender differences in circadian rhythm amplitude of inflammation, melatonin, and oxidative stress in CKD animals, probably in favor of female sex steroids. These findings emphasize on the importance of gender differences in CKD progression; therefore, considerable attention must be paid to gender in the treatment of CKD.Introduction. Circadian system is deeply involved in renal function. The circadian timing system may be disrupted in chronic kidney disease (CKD) patients. Gender differences in CKD have been reported. This research aimed to investigate the gender differences in the circadian rhythm of inflammatory and oxidant markers of CKD. Methods. Male, intact female, and ovariectomized (OVX) female rats (twenty-four in each group) were randomly assigned to control and CKD groups. The rats were further divided into day (12:00 p.m.) and night (12:00 a.m.) subgroups. Evaluations of each sample were carried out a day after the last day of adenine administration. Results. Final results revealed that the circadian rhythm of plasma melatonin , kidney malondialdehyde (MDA), and transforming growth factor- β (TGF-β) levels in CKD group were the same as the control group. Melatonin and total antioxidant capacity (TAC) levels significantly decreased in the CKD group compared with the control group in day and night subgroups, whereas MDA and TGF-β levels increased. Male group in comparison with the intact female group significantly showed less melatonin and TAC but higher MDA and TGF-β levels which could be due to CKD. Conclusion. Findings of this study represent gender differences in circadian rhythm amplitude of inflammation, melatonin, and oxidative stress in CKD animals, probably in favor of female sex steroids. These findings emphasize on the importance of gender differences in CKD progression; therefore, considerable attention must be paid to gender in the treatment of CKD. DOI: 10.52547/ijkd.6242

Effects of exogenous melatonin on sleep and circadian rhythms in women with premenstrual dysphoric disorder.

We previously found normal polysomnographic (PSG) sleep efficiency, increased slow-wave sleep (SWS), and a blunted melatonin secretion in women with premenstrual dysphoric disorder (PMDD) compared to controls. Here, we investigated the effects of exogenous melatonin in five patients previously studied. They took 2 mg of slow-release melatonin 1 h before bedtime during their luteal phase (LP) for three menstrual cycles. At baseline, patients spent every third night throughout one menstrual cycle sleeping in the laboratory. Measures included morning urinary 6-sulfatoxymelatonin (aMt6), PSG sleep, nocturnal core body temperature (CBT), visual analog scale for mood (VAS-Mood), Prospective Record of the Impact and Severity of Menstrual Symptoms (PRISM), and ovarian plasma hormones. Participants also underwent two 24-hour intensive physiological monitoring (during the follicular phase and LP) in time-isolation/constant conditions to determine 24-hour plasma melatonin and CBT rhythms. The same measures were repeated during their third menstrual cycle of melatonin administration. In the intervention condition compared to baseline, we found increased urinary aMt6 (p < 0.001), reduced objective sleep onset latency (p = 0.01), reduced SWS (p < 0.001), and increased Stage 2 sleep (p < 0.001). Increased urinary aMt6 was correlated with reduced SWS (r = -0.51, p < 0.001). Circadian parameters derived from 24-hour plasma melatonin and CBT did not differ between conditions, except for an increased melatonin mesor in the intervention condition (p = 0.01). Ovarian hormones were comparable between the conditions (p ≥ 0.28). Symptoms improved in the intervention condition, as measured by the VAS-Mood (p = 0.02) and the PRISM (p < 0.001). These findings support a role for disturbed melatonergic system in PMDD that can be partially corrected by exogenous melatonin.

738 Effects of exogenous melatonin on sleep, circadian rhythms, and mood in women with premenstrual dysphoric disorder

Abstract Introduction Most women with premenstrual dysphoric disorder (PMDD) report sleep disturbances. Our group found normal polysomnographic (PSG) sleep efficiency and increased slow wave sleep (SWS) across the menstrual cycle in women with PMDD and insomnia compared to controls. Reduced melatonin levels were found in PMDD women compared to controls, with reduced secretion during their luteal phase (LP) compared to follicular phase (FP). Here, we investigated the effects of exogenous melatonin in the patients we previously studied. Methods Five patients (age, mean: 33.6, SD: 2.7) diagnosed prospectively with PMDD and insomnia participated in the study. Following a baseline assessment, patients took 2 mg of slow-release melatonin 1h before bedtime during their LP for three consecutive menstrual cycles. At baseline (treatment-free condition), patients spent every third night of their menstrual cycle sleeping in the laboratory. Measures included morning urinary 6-sulfatoxymelatonin (aMt6), PSG sleep, nocturnal core body temperature (CBT), visual analogue scale for mood (VAS-Mood), Prospective Record of the Impact and Severity of Menstrual symptoms (PRISM), subjective sleep and ovarian hormones (estrogen and progesterone). Participants also underwent two 24-hour intensive physiological monitoring (during the FP and LP) in time-isolation/constant conditions to determine 24-hour plasma melatonin and CBT rhythms. The same measures were repeated during their third menstrual cycle of melatonin administration. Results In the intervention condition compared to baseline, we found increased urinary aMt6 (p&amp;lt;0.001), reduced objective SOL (p=0.01), SWS (p&amp;lt;0.001) and increased Stage 2 sleep (p&amp;lt;0.001). Increased urinary aMt6 was associated with reduced SWS (r=-0.51, p&amp;lt;0.001). Circadian parameters derived from 24-hour plasma melatonin and CBT did not differ between conditions, except for an increased melatonin mesor in the intervention condition (p=0.01). Ovarian hormones were comparable between the conditions (p≥0.28). Symptoms improved in the intervention condition, as measured by the VAS-Mood (p=0.02) and the PRISM (p&amp;lt;0.001). Conclusion We have shown normalization of SWS and reduction in self-reported mood and somatic symptoms after administrating exogenous melatonin in women with PMDD. These findings support a role for disturbed melatoninergic system in PMDD that can be partially corrected by exogenous melatonin. Support (if any) This study was supported by the Canadian Institutes of Health Research (CIHR)

Diurnal Rhythm of Plasma Melatonin Concentration in the Domestic Turkey and Its Regulation by Light and Endogenous Oscillators.

Simple SummaryEnvironmental light regulates a wide range of phenomena in almost all organisms on Earth. Daily and seasonal changes in the photoperiod duration are the most important factors controlling the secretion of melatonin (MLT), a pineal hormone that affects many physiological processes in birds. The results of previous studies on the effect of MLT on the productivity and health of poultry have been promising. However, there are very few studies on the daily profiles of plasma MLT concentrations in domestic birds; therefore, we decided to examine plasma MLT levels in 10-week-old domestic turkeys exposed to different light conditions. The results demonstrated that plasma MLT concentration in turkeys kept under a 12 h light: 12 h dark cycle showed a prominent diurnal rhythm. Night-time light exposure caused a rapid decrease in plasma MLT concentrations. The housing of turkeys in continuous dim red light revealed endogenously generated diurnal rhythm of MLT secretion. The rhythm of the plasma MLT level in a reversed cycle of 12 h dark: 12 h light adapted quickly to the new lighting condition. The aim of this study was to characterize the diurnal rhythm of plasma melatonin (MLT) concentration and its regulation by light and endogenous oscillators in 10-week-old domestic turkeys. Three experiments were performed to examine (i) the course of daily changes in plasma MLT concentration in turkeys kept under a 12 h light: 12 h dark (12L:12D) cycle; (ii) the influence of night-time light exposure lasting 0.5, 1, 2, or 3 h on the plasma MLT level; and (iii) the occurrence of circadian fluctuations in plasma MLT levels in birds kept under continuous dim red light and the ability of turkeys to adapt their pineal secretory activity to a reversed light-dark cycle (12D:12L). The plasma MLT concentration was measured with a direct radioimmunoassay. The plasma MLT concentration in turkeys kept under a 12L:12D cycle changed significantly in a daily rhythm. It was low during the photophase and increased stepwise after the onset of darkness to achieve the maximal level in the middle of the scotophase. Next, it decreased during the second half of the night. The difference between the lowest level of MLT and the highest level was approximately 18-fold. The exposure of turkeys to light during the scotophase caused a rapid, large decrease in plasma MLT concentration. The plasma MLT concentration decreased approximately 3- and 10-fold after 0.5 and 1 h of light exposure, respectively, and reached the day-time level after 2 h of exposure. In turkeys kept under continuous darkness, the plasma MLT level was approximately 2.5-fold higher at 02:00 h than at 14:00 h. In birds kept under 12D:12L, the plasma MLT level was significantly higher at 14:00 h than at 02:00 h. The results showed that plasma MLT concentrations in 10-week-old turkeys have a prominent diurnal rhythm, which is endogenously generated and strongly influenced by environmental light.

Effect of acute total sleep deprivation on plasma melatonin, cortisol and metabolite rhythms in females.

Disruption to sleep and circadian rhythms can impact on metabolism. The study aimed to investigate the effect of acute sleep deprivation on plasma melatonin, cortisol and metabolites, to increase understanding of the metabolic pathways involved in sleep/wake regulation processes. Twelve healthy young female participants remained in controlled laboratory conditions for ~92 hr with respect to posture, meals and environmental light (18:00–23:00 hr and 07:00‐09:00 hr <8 lux; 23:00–07:00 hr 0 lux (sleep opportunity) or <8 lux (continuous wakefulness); 09:00–18:00 hr ~90 lux). Regular blood samples were collected for 70 hr for plasma melatonin and cortisol, and targeted liquid chromatography–mass spectrometry metabolomics. Timepoints between 00:00 and 06:00 hr for day 1 (baseline sleep), day 2 (sleep deprivation) and day 3 (recovery sleep) were analysed. Cosinor analysis and MetaCycle analysis were performed for detection of rhythmicity. Night‐time melatonin levels were significantly increased during sleep deprivation and returned to baseline levels during recovery sleep. No significant differences were observed in cortisol levels. Of 130 plasma metabolites quantified, 41 metabolites were significantly altered across the study nights, with the majority decreasing during sleep deprivation, most notably phosphatidylcholines. In cosinor analysis, 58 metabolites maintained their rhythmicity across the study days, with the majority showing a phase advance during acute sleep deprivation. This observation differs to that previously reported for males. Our study is the first of metabolic profiling in females during sleep deprivation and recovery sleep, and offers a novel view of human sleep/wake regulation and sex differences.

The Effects of Naturalistic Light on Diurnal Plasma Melatonin and Serum Cortisol Levels in Stroke Patients during Admission for Rehabilitation: A Randomized Controlled Trial.

Background: Stroke patients admitted for rehabilitation often lack sufficient daytime blue light exposure due to the absence of natural light and are often exposed to light at unnatural time points.We hypothesized that artificial light imitating daylight, termed naturalistic light, would stabilize the circadian rhythm of plasma melatonin and serum cortisol levels among long-term hospitalized stroke patients.Methods: A quasi-randomized controlled trial. Stroke patients in need of rehabilitation were randomized between May 1, 2014, and June 1, 2015 to either a rehabilitation unit equipped entirely with always on naturalistic lighting (IU), or to a rehabilitation unit with standard indoor lighting (CU). At both inclusion and discharge after a hospital stay of at least 2 weeks, plasma melatonin and serum cortisol levels were measured every 4 hours over a 24-hour period. Circadian rhythm was estimated using cosinor analysis, and variance between time-points.Results: A total of 43 were able to participate in the blood collection. Normal diurnal rhythm of melatonin was disrupted at both inclusion and discharge. In the IU group, melatonin plasma levels were increased at discharge compared to inclusion (n = 23; median diff, 2.9; IQR: -1.0 to 9.9, p = 0.030) and rhythmicity evolved (n = 23; p = 0.007). In the CU group, melatonin plasma levels were similar between discharge and inclusion and no rhythmicity evolved. Overall, both patient groups showed normal cortisol diurnal rhythms at both inclusion and discharge.Conclusions: This study is the first to demonstrate elevated melatonin plasma levels and evolved rhythmicity due to stimulation with naturalistic light.

Meagre's melatonin profiles under captivity: circadian rhythmicity and light sensitiveness.

The present study reveals the first characterization of the plasma melatonin rhythms of the meagre (Argyrosomus regius) under aquaculture conditions. Melatonin levels were monitored during a 24h cycle under a photoperiod of 16L:8D and under constant darkness (DD), respectively to characterize the daily rhythm of this indoleamine and to test its endogenous origin. Besides, to identify which light intensities are perceived as night or day by this species, the degree of inhibition of nocturnal melatonin production caused by increasing intensities of light was tested (3.3, 5.3, 10.5, and 120μW/cm2), applying 1h light pulses at Mid-Dark. The result for melatonin daily rhythm in plasma showed a typical profile: concentration remained low during all daytime points, increasing greatly during dark points, with maximum values at 16:00 and 22:00h, zeitgeber time. Under DD conditions, the plasma melatonin profile persisted, with a similar acrophase but with a lower amplitude between subjective day and night periods, indicating this rhythm as being endogenously driven. Moreover, meagre seemed to be very sensitive to dim levels of illumination during the night, since an intensity of just 3.3μW/cm2 inhibited melatonin production. However, only the pulse of 5.3μW/cm2 caused a melatonin drop till daytime concentrations. Thus, the threshold of light detection by the pineal organ was suggested as being located between 3.3 and 5.3μW/cm2. Such results are an added value for this species biology knowledge, and in consequence to its adaptation to aquaculture conditions, allowing the improvement of culture husbandry protocols.

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.

Effect of caloric restriction on plasma melatonin levels in aged rhesus macaques

In this study, we examined the 24-hour plasma melatonin patterns of young adult (∼11 years of age) and old (∼24 years of age) rhesus macaques, and determined how they would be influenced by 30% caloric restriction (CR). Well-defined 24-hour plasma melatonin rhythms were observed in all the males but only the old animals showed significant attenuation of night-time melatonin levels. Moreover, 4.5 years of CR failed to prevent the age-associated decline in plasma melatonin levels in the old males and caused a significant decrease in the young adult males. Similar plasma melatonin rhythms were also observed in all the females but no age-related decline was detected, and 2 years of CR had no obvious effect on plasma melatonin levels. If anything, there was a trend for the CR to decrease melatonin levels in the young adult females. Taken together, the results fail to show any clear benefit of CR on plasma melatonin levels in old rhesus macaques and may even be detrimental to plasma melatonin levels in young adults.

Gestational Chronodisruption Impairs Circadian Physiology in Rat Male Offspring, Increasing the Risk of Chronic Disease.

Chronic exposure to light at night, as in shift work, alters biological clocks (chronodisruption), negatively impacting pregnancy outcome in humans. Actually the interaction of maternal and fetal circadian systems could be a key factor determining a fitting health in adults. We propose that chronic photoperiod shift (CPS) during pregnancy alter maternal circadian rhythms and impair circadian physiology in the adult offspring, increasing health risks. Pregnant rats were exposed to normal photoperiod (12 h light, 12 h dark) or to CPS until 85% of gestation. The effects of gestational CPS were evaluated on the mother and adult offspring. In the mother we measured rhythms of heart rate, body temperature, and activity through gestation and daily rhythms of plasma variables (melatonin, corticosterone, aldosterone, and markers of renal function) at 18 days of gestation. In adult offspring, we measured rhythms of the clock gene expression in the suprachiasmatic nucleus (SCN), locomotor activity, body temperature, heart rate, blood pressure, plasma variables, glucose tolerance, and corticosterone response to ACTH. CPS altered all maternal circadian rhythms, lengthened gestation, and increased newborn weight. The adult CPS offspring presented normal rhythms of clock gene expression in the SCN, locomotor activity, and body temperature. However, the daily rhythm of plasma melatonin was absent, and corticosterone, aldosterone, renal markers, blood pressure, and heart rate rhythms were altered. Moreover, CPS offspring presented decreased glucose tolerance and an abnormal corticosterone response to ACTH. Altogether these data show that gestational CPS induced long-term effects on the offspring circadian system, wherein a normal SCN coexists with altered endocrine, cardiovascular, and metabolic function.

Morning and evening physical exercise differentially regulate the autonomic nervous system during nocturnal sleep in humans.

Effects of daily physical exercise in the morning or in the evening were examined on circadian rhythms in plasma melatonin and core body temperature of healthy young males who stayed in an experimental facility for 7 days under dim light conditions (<10 lux). Sleep polysomnogram (PSG) and heart rate variability (HRV) were also measured. Subjects performed 2-h intermittent physical exercise with a bicycle ergometer at ZT3 or at ZT10 for four consecutive days, where zeitgeber time 0 (ZT0) was the time of wake-up. The rising phase of plasma melatonin rhythm was delayed by 1.1 h without exercise. Phase-delay shifts of a similar extent were detected by morning and evening exercise. But the falling phase shifted only after evening exercise by 1.0 h. The sleep PSG did not change after morning exercise, while Stage 1+2 sleep significantly decreased by 13.0% without exercise, and RE sleep decreased by 10.5% after evening exercise. The nocturnal decline of rectal temperature was attenuated by evening exercise, but not by morning exercise. HRV during sleep changed differentially. Very low frequency (VLF) waves increased without exercise. VLF, low frequency (LF), and high frequency (HF) waves increased after morning exercise, whereas HR increased after evening exercise. Morning exercise eventually enhanced the parasympathetic activity, as indicated by HRV, while evening exercise activated the sympathetic activity, as indicated by increase in heart rate in the following nocturnal sleep. These findings indicated differential effects of morning and evening exercise on the circadian melatonin rhythm, PSG, and HRV.

Seasons induce changes in the daily rhythm of plasma melatonin in goats (Capra hircus)

To evaluate the influence of natural photoperiod on the daily rhythm of melatonin, we assessed melatonin plasma concentration at four different times of the year. Ten Sarda breed goats were led to the natural pasture during the day and were kept in a common stall during the night. Blood samples were collected by means of a cannula inserted into the jugular vein, every two hours for a 24-hour period during the vernal equinox, summer solstice, autumn equinox, and winter solstice. Our results showed the existence of clear seasonal variation in the daily rhythm of plasma melatonin in goats, with the highest MESOR value in winter followed by spring. Acrophase was always observed in the middle of the scotophase. Robustness of the rhythm was higher in the spring as compared to the winter. Our results showed a daily rhythm of plasma melatonin concentration strongly related to the seasons. These results could be useful to establish appropriately timed melatonin and/or photoperiod treatments for the management of reproductive physiology in goats.

The effects of the duration and onset of light stimulation during incubation on the behavior, plasma melatonin levels, and productivity of broiler chickens1

Light stimulation during incubation can affect the behavior, health, and performance of poultry posthatch. However, there has been relatively little work systematically assessing the pattern of light stimulation needed to produce these effects or the mechanism underlying them. We conducted 2 experiments to assess the effects of duration and onset of light exposure during incubation on Cobb 500 broiler chickens. In the first, eggs (n = 1,404) were incubated under photoperiods of either 0 h of light and 24 h of darkness (0 L:24 D), 1 h of light and 23 h of darkness (1 L:23 D), 6 h of light and 18 h of darkness (6L:18D), or 12 h of light and 12 h of darkness (12L:12D). In the second, eggs (n = 1,008) were incubated in either complete darkness or under 12L:12D, which was applied either for the entire incubation period or with light onset beginning at either 7 or 14 d of incubation. Broilers were then housed in floor pens under a 12L:12D cycle posthatch. Measurements included performance outcomes, plasma melatonin, general behavioral activity assessed using passive infrared detection, and feeding activity assessed using automated continuous monitoring of feed intake at wk 5 of age. There were no treatment differences in hatchability, mortality, growth, feed consumption, feed conversion ratio, overall feeding behavior activity, or general behavioral activity over a 24-h period in either experiment. However, broilers incubated under 12L:12D fed more (P < 0.05) than the 0 L:24 D broilers during the first 3 h after the lights came on in Exp. 1 and during the first hour after the lights came on in Exp. 2. In Exp. 1, general activity levels measured using passive infrared detection at night also differed (P = 0.05), with 0 L:24 D more active than 12L:12D. There was a treatment difference between the 0 L:12 D and 12 L:12 D in their plasma melatonin rhythms during d 19 of incubation, but this difference had disappeared when broilers were sampled at wk 5 posthatch. The results of this study indicate that providing 12 h of light during incubation can have a long-lasting effect on the diurnal rhythms of behavior, although the mechanism underlying this does not appear to be related to a persistent change in melatonin rhythm.

Pilot Investigation of the Circadian Plasma Melatonin Rhythm across the Menstrual Cycle in a Small Group of Women with Premenstrual Dysphoric Disorder

Women with premenstrual dysphoric disorder (PMDD) experience mood deterioration and altered circadian rhythms during the luteal phase (LP) of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP) and LP of the menstrual cycle, consisting of intensive physiological monitoring under “unmasked”, time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03) worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025) increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05) decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed.

Photoperiodic lighting (16 hours of light:8 hours of dark) programs during incubation: 1. Effects on growth and circadian physiological traits of embryos and early stress response of broiler chickens

This study was conducted to evaluate the effect of a 16L:8D photoperiod during incubation, either during the whole incubation period (Inc(0-21d)) or the last week of incubation (Inc(14-21d)), on embryo growth, incubation performance, and light:dark rhythm of plasma melatonin and corticosterone in relation to early stress responses of newly hatched chicks to the posthatching environment. A dark incubation condition (Inc(Dark)) served as control. Three batches of eggs (n = 1,080, 1,320, 720) from Ross 308 broiler breeders were used in the experiment. Embryos from Inc(0-21d) presented a daily rhythm of melatonin at internal pipping and hatching, but Inc(Dark) embryos did not. The Inc(14-21d) group had rhythmic plasma melatonin at hatching only. A L:D rhythm of corticosterone was apparent at hatching. A significant incubation × sampling time interaction suggested that a lower increment in blood corticosterone level in Inc(0-21d) at 8 h posthatching (light period), as compared with hatching (dark period) values, might be associated with probable changes in the hypothalamic-pituitary-adrenal axis in Inc(0-21d) through incubation lighting. This finding may also suggest improved adaptation to the posthatching environment. Incubation lighting did not consistently affect brain malondialdehyde concentration; the only difference between groups was higher concentrations at hatching in Inc(14-21d), whereas incubation groups at the internal pipping stage had similar values. Mean relative asymmetry (RA) did not differ with incubation lighting. The malondialdehyde and RA results indicate that neither lighting nor darkness during the overall incubation exacerbated embryo oxidative and developmental stress. An increased breast muscle weight was observed at hatching only in Inc(14-21d). The Inc(0-21d) group had increased embryo weights relative to egg weight and decreased residual yolk but had no effect on chick weight, relative heart and liver (% of embryo weight), hatchability, embryo mortality, incubation time, oxidative stress, or mean RA. In conclusion, these results provide further evidence that photoperiodic lighting during incubation (Inc(0-21d)) may improve adaptation of chicks to a novel environment at hatching, possibly giving birds a better start for early posthatching development.

Effects of 1800-MHz Radiofrequency Fields on Circadian Rhythm of Plasma Melatonin and Testosterone in Male Rats

Radiofrequency fields (RF) at 1800 MHz are known to affect melatonin (MEL) and testosterone in male rats, but it remains to be determined whether RF affected circadian rhythm of these plasma hormones. Male Sprague-Dawley rats were exposed to 1800-MHz RF at 208 μw/cm2 power density (SAR: 0.5762 W/kg) at different zeitgeber (ZT) periods of the day, including 0 (ZT0), 4 (ZT4), 8 (ZT8), 12 (ZT12), 16 (ZT16), and 20 (ZT20) h. RF exposure was 2 h/d for 32 d. From each rat, the concentrations of plasma MEL and testosterone were determined in plasma after RF exposure and compared with controls. The results confirmed the existence of circadian rhythms in the synthesis of MEL and testosterone, but revealed an inverse relationship in peak phase of these rhythms. These rhythms were disturbed after exposure to RF, with the effect being more pronounced on MEL than testosterone. The most pronounced effect of RF exposure on MEL and testosterone appears to be in rats exposed to RF at ZT 16 and ZT0 h, respectively. Data suggest that regulation of testosterone is controlled by MEL and that MEL is more sensitive to RF exposure.

Timed Maternal Melatonin Treatment Reverses Circadian Disruption of the Fetal Adrenal Clock Imposed by Exposure to Constant Light

Surprisingly, in our modern 24/7 society, there is scant information on the impact of developmental chronodisruption like the one experienced by shift worker pregnant women on fetal and postnatal physiology. There are important differences between the maternal and fetal circadian systems; for instance, the suprachiasmatic nucleus is the master clock in the mother but not in the fetus. Despite this, several tissues/organs display circadian oscillations in the fetus. Our hypothesis is that the maternal plasma melatonin rhythm drives the fetal circadian system, which in turn relies this information to other fetal tissues through corticosterone rhythmic signaling. The present data show that suppression of the maternal plasma melatonin circadian rhythm, secondary to exposure of pregnant rats to constant light along the second half of gestation, had several effects on fetal development. First, it induced intrauterine growth retardation. Second, in the fetal adrenal in vivo it markedly affected the mRNA expression level of clock genes and clock-controlled genes as well as it lowered the content and precluded the rhythm of corticosterone. Third, an altered in vitro fetal adrenal response to ACTH of both, corticosterone production and relative expression of clock genes and steroidogenic genes was observed. All these changes were reversed when the mother received a daily dose of melatonin during the subjective night; supporting a role of melatonin on overall fetal development and pointing to it as a ‘time giver’ for the fetal adrenal gland. Thus, the present results collectively support that the maternal circadian rhythm of melatonin is a key signal for the generation and/or synchronization of the circadian rhythms in the fetal adrenal gland. In turn, low levels and lack of a circadian rhythm of fetal corticosterone may be responsible of fetal growth restriction; potentially inducing long term effects in the offspring, possibility that warrants further research.