Dysregulation of circadian rhythms following prolactin-secreting pituitary microadenoma

A patient who developed an irregular sleep-wake pattern following prolactin-secreting pituitary microadenoma is described. The patient reported difficulties in sleep onset and awakening at the desired time, which caused major dysfunction in his daily life activities. Despite these difficulties, the sleep-related complaints of the patient remained unrecognized for as long as three yrs. Statistical analyses of the patient's rest-activity patterns revealed that the disruption of the sleep-wake circadian rhythm originated from a disharmony between ultradian (semicircadian) and circadian components. The circadian component displayed shorter than 24 h periodicity most of the time, but the semicircadian component fluctuated between longer and shorter than 12 h periods. Additionally, desynchrony in terms of period length was found in the tentative analyses of the rest-activity pattern, salivary melatonin, and oral temperature. While the salivary melatonin time series data could be characterized by a best-fit cosine curve of 24 h, the time series data of oral temperature was more compatible with 28 h best-fit curve. The rest-activity cycle during the simultaneous measurements, however, was best approximated by a best-fit curve of 21 h. The dysregulation of circadian rhythms occurred concomitantly, but not beforehand, with the onset of pituitary disease, thus suggesting an association between the two phenomena. This association may have interesting implications to the modeling of the circadian time-keeping system. This case also highlights the need to raise the awareness to circadian rhythm sleep disorders and to consider disruptions of sleep-wake cycle in patients with pituitary adenoma.     

Phase-synchronization of daily motor activities can reveal differential circadian patterns

The aim of the study was to determine any alteration of the 24 h motor activity pattern of a bipolar patient in different mood states. Actigraphic records were collected on an outpatient basis for a total of 387 days. The daily actograms were synchronized in phase to the time of morning awakening before averaging, which significantly enhanced the structure of the averaged traces. The actograms were divided into three groups based on total daily count. The daily motor activity patterns of the low- and high-activity days have a different circadian pattern. We propose it may have a relevance to the different mood states. The phase-synchronization of the 24 h actograms to the patient's sleep-wake cycle, specifically to the time of awaking from the nighttime sleep, may help reveal differences in the daily temporal patterns of motor activity.     

Linear demasking techniques are unreliable for estimating the circadian phase of ambulatory temperature data.

Clinical investigators often use ambulatory temperature monitoring to assess the endogenous phase and amplitude of an individual's circadian pacemaker for diagnostic and research purposes. However, an individual's daily schedule includes changes in levels of activity, in posture, and in sleep-wake state, all of which are known to have masking or evoked effects on core body temperature (CBT) data. To compensate for or to correct these masking effects, many investigators have developed "demasking" techniques to extract the underlying circadian phase and amplitude data. However, the validity of these methods is uncertain. Therefore, the authors tested a variety of analytic methods on two different ambulatory data sets from two different studies in which the endogenous circadian pacemaker was not synchronized to the sleep-wake schedule. In both studies, circadian phase estimates calculated from CBT collected when each subject was ambulatory (i.e., free to perform usual daily activities) were compared to those calculated during the same study when the same subject's activities were controlled. In the first study, 24 sighted young and older subjects living on a 28-h scheduled "day" protocol were studied for approximately 21 to 25 cycles of 28-h each. In the second study, a blind man whose endogenous circadian rhythms were not synchronized to the 24-h day despite his maintenance of a regular 24-h sleep-wake schedule was studied for more than 80 consecutive 24-h days. During both studies, the relative phase of the endogenous (circadian) and evoked (scheduled activity-rest) components of the ambulatory temperature data changed progressively and relatively slowly, enabling analysis of the CBT rhythm at nearly all phase relationships between the two components. The analyses of the ambulatory temperature data demonstrate that the masking of the CBT rhythm evoked by changes in activity levels, posture, or sleep-wake state associated with the evoked schedule of activity and rest can significantly obscure the endogenous circadian component of the signal, the object of study. In addition, the masking effect of these evoked responses on temperature depends on the circadian phase at which they occur. These nonlinear interactions between circadian phase and sleep-wake schedule render ambulatory temperature data unreliable for the assessment of endogenous circadian phase. Even when proposed algebraic demasking techniques are used in an attempt to reveal the endogenous temperature rhythm, the phase estimates remain severely compromised.     

Working under daylight intensity lamp: an occupational risk for developing circadian rhythm sleep disorder?

A 47-yr-old male was admitted to the Institute for Fatigue and Sleep Medicine complaining of severe fatigue and daytime sleepiness. His medical history included diagnosis of depression and chronic fatigue syndrome. Antidepressant drugs failed to improve his condition. He described a gradual evolvement of an irregular sleep-wake pattern within the past 20 yrs, causing marked distress and severe impairment of daily functioning. He had to change to a part-time position 7 yrs ago, because he was unable to maintain a regular full-time job schedule. A 10-day actigraphic record revealed an irregular sleep-wake pattern with extensive day-to-day variability in sleep onset time and sleep duration, and a 36 h sampling of both melatonin level and oral temperature (12 samples, once every 3 h) showed abnormal patterns, with the melatonin peak around noon and oral temperature peak around dawn. Thus, the patient was diagnosed as suffering from irregular sleep-wake pattern. Treatment with melatonin (5 mg, 2 h before bedtime) did not improve his condition. A further investigation of the patient's daily habits and environmental conditions revealed two important facts. First, his occupation required work under a daylight intensity lamp (professional diamond-grading equipment of more than 8000 lux), and second, since the patient tended to work late, the exposure to bright light occurred mostly at night. To recover his circadian rhythmicity and stabilize his sleep-wake pattern, we recommended combined treatment consisting of evening melatonin ingestion combined with morning (09:00 h) bright light therapy (0800 lux for 1 h) plus the avoidance of bright light in the evening. Another 10-day actigraphic study done only 1 wk after initiating the combined treatment protocol revealed stabilization of the sleep-wake pattern with advancement of sleep phase. In addition, the patient reported profound improvement in maintaining wakefulness during the day. This case study shows that chronic exposure to bright light at the wrong biological time, during the nighttime, may have serious effects on the circadian sleep-wake patterns and circadian time structure. Therefore, night bright light exposure must be considered to be a risk factor of previously unrecognized occupational diseases of altered circadian time structure manifested as irregularity of the 24 h sleep-wake cycle and melancholy.     

Can dim light melatonin onset be predicted by the timing of sleep in patients with possible circadian sleep-wake rhythm disorders?

Dim Light Melatonin Onset (DLMO) is a reliable marker of the endogenous circadian rhythm. To determine if sleep timing can predict DLMO, we investigated the relationship between sleep timing and DLMO in patients in various circadian sleep-wake rhythm disorders (CSWRDs), ages and genders. We found that correlations were only moderate between DLMO and sleep-onset in the complete data-set, but they increased in patients with delayed sleep-wake phase disorder (DSWPD), DSWPD patients with a regular sleep pattern and patients with advanced sleep-wake phase disorder (ASWPD); the levels of correlation were r = 0.542, 0.657, 0.728 and 0.814, respectively. In DSWPD patients with a regular sleep pattern, mid-sleep strongly correlated (r = 0.839) with DLMO. Correlation in other CSRWDs was not significant. DLMO, sleep-onset and age were most discriminated factors between the various CSRWDs. Estimation of DLMO is only possible in patients with ASWPD and in DSWPD patients with a regular sleep pattern.     

Integration of human sleep-wake regulation and circadian rhythmicity.

The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular-genetic correlates of circadian sleep disorders suggest that the timing of the sleep-wake cycle and circadian rhythms is closely integrated but is, in part, regulated differentially.     

Disorders of Orcadian Body Temperature Rhythm in Severely Brain-Damaged Patients

Twenty-four hour patterns of body temperature (BT) were recorded during consecutive 3-10 day spans from 14 severely brain-damaged patients. Seven patients exhibited a normal circadian BT rhythm with an amplitude of more than 1°C and a normal phase position of the minimum BT being observed during the latter half of the nocturnal sleep. One patient with a dispersed type of sleep exhibited an extremely low amplitude of the BT rhythm with mean average 0.69°C. In this patient, an 24-hr observation span was insufficient to detect the existence of a BT rhythm. Two patients manifested disturbance of period. As acrophase of the BT rhythm varied from day to day, the standard deviation (S.D.) of mean acrophase wasextremely large. For these patients the light-dark cycle did not act as an entrainer because both had visual disturbance. A phase advance of the minimum BT was observed in four patients. The minimum BT appeared in the first half of nocturnal sleep. These three disturbances (amplitude, period and phase), were revealed only by longitudinal observation of the BT rhythm, indicating the importance of long-term observations over a sufficient period to make the nature of the rhythm disturbances clear. These disturbances were not related to that of the sleep-wake cycle, as two patients showed normal circadian BT rhythm in spite of their dispersed-type sleep.     

A three-oscillator model of the human circadian system controlling the core temperature rhythm and the sleep-wake cycle

Even during “free-running” experiments, in which subjects lived in caves or cellars without any time cues, various circadian rhythms such as core body temperature and the sleep-wake cycle remained for a long time mutually synchronized in one group of subjects. In another group of subjects, or later in the same subjects, a number of unusually long sleep-wake cycles occurred while body temperature persisted in a near-24 hr rhythm. This has been termed “internal desynchronization” by Aschoff & Wever (1962) to emphasize the uncoupling of rhythms. Zulley (1980) and Czeisler et al. (1980) found that the duration of sleep depends regularly on the phase of the sleep onset in the body temperature rhythm, even in the apparently “random and irregular” sleep-wake pattern. The graph which plots, the sleep duration against the sleep onset phase is called sleep duration in this paper. We develop a quantitative, multi-oscillator model of human circadian system following Wever (1979) and Kronauer et al. (1982). Because the simplest model, which describes the state of each component oscillator by only one variable (ptlase) was adopted for each component oscillator, we can determine the intFraction between oscillators using sleep duration. It is found that a three-oscillator model can simulate several qualitative features of human circadian rhythms, such as an irregular free-running pattern and sleep duration. Moreover we find that the model reproduces the mysterious phenomenon of “forbidden wake up”, although we do not incorporate a priori any mechanism to explain it.     

Regression Models for the Estimation of Orcadian Rhythms in the Presence of Effects Due to Masking

The estimation of human circadian rhythms from experimental data is complicated by the presence of “masking” effects associated with the sleep-wake cycle. The observed rhythm may include a component due to masking, as well as the endogenous component linked to a circadian pacemaker. In situations where the relationship between the sleep-wake cycle and the circadian rhythm is not constant, it may be possible to obtain individual estimates of these two components, but methods commonly used for the estimation of circadian rhythms, such as the cosinor analysis, spectral analysis, average waveforms and complex demodulation, have not generally been adapted to identify the modulations that arise from masking. The estimates relate to the observed rhythms, and the amplitudes and acrophases do not necessarily refer to the endogenous rhythm.

In this paper methods are discussed for the separation of circadian and masking effects using regression models that incorporate a sinusoidal circadian variation together with functions of time since sleep and time during sleep. The basic model can be extended to include a time-varying circadian rhythm and estimates are available for the amplitude and phase at a given time, together with their joint confidence intervals and tests for changes in amplitude and acrophase between any two selected times. Modifications of these procedures are discussed to allow for non-sinusoidal circadian rhythms, non-additivity of the circadian and time-since-sleep effects and the breakdown of the usual assumptions concerning the residual errors.

This approach enables systematic masking effects associated with the sleep-wake cycle to be separated from the circadian rhythm, and it has applications to the analysis of data from experiments where the sleep-wake cycle is not synchronized with the circadian rhythm, for example after time-zone transitions or during irregular schedules of work and rest.     

A phase dynamics model of human circadian rhythms

Nonphotic entrainment of an overt sleep-wake rhythm and a circadian pacemaker-driving temperature/melatonin rhythm suggests existence of feedback mechanisms in the human circadian system. In this study, the authors constructed a phase dynamics model that consisted of two oscillators driving temperature/melatonin and sleep-wake rhythms, and an additional oscillator generating an overt sleep-wake rhythm. The feedback mechanism was implemented by modifying couplings between the constituent oscillators according to the history of correlations between them. The model successfully simulated the behavior of human circadian rhythms in response to forced rest-activity schedules under free-run situations: the sleep-wake rhythm is reentrained with the circadian pacemaker after release from the schedule, there is a critical period for the schedule to fully entrain the sleep-wake rhythm, and the forced rest-activity schedule can entrain the circadian pacemaker with the aid of exercise. The behavior of human circadian rhythms was reproduced with variations in only a few model parameters. Because conventional models are unable to reproduce the experimental results concerned here, it was suggested that the feedback mechanisms included in this model underlie nonphotic entrainment of human circadian rhythms.     

Rhythms in Fos expression in brain areas related to the sleep-wake cycle in the diurnal Arvicanthis niloticus

Most mammals show daily rhythms in sleep and wakefulness controlled by the primary circadian pacemaker, the suprachiasmatic nucleus (SCN). Regardless of whether a species is diurnal or nocturnal, neural activity in the SCN and expression of the immediate-early gene product Fos increases during the light phase of the cycle. This study investigated daily patterns of Fos expression in brain areas outside the SCN in the diurnal rodent Arvicanthis niloticus. We specifically focused on regions related to sleep and arousal in animals kept on a 12:12-h light-dark cycle and killed at 1 and 5 h after both lights-on and lights-off. The ventrolateral preoptic area (VLPO), which contained cells immunopositive for galanin, showed a rhythm in Fos expression with a peak at zeitgeber time (ZT) 17 (with lights-on at ZT 0). Fos expression in the paraventricular thalamic nucleus (PVT) increased during the morning (ZT 1) but not the evening activity peak of these animals. No rhythm in Fos expression was found in the centromedial thalamic nucleus (CMT), but Fos expression in the CMT and PVT was positively correlated. A rhythm in Fos expression in the ventral tuberomammillary nucleus (VTM) was 180 degrees out of phase with the rhythm in the VLPO. Furthermore, Fos production in histamine-immunoreactive neurons of the VTM cells increased at the light-dark transitions when A. niloticus show peaks of activity. The difference in the timing of the sleep-wake cycle in diurnal and nocturnal mammals may be due to changes in the daily pattern of activity in brain regions important in sleep and wakefulness such as the VLPO and the VTM.     

Myotonic dystrophytype 1 – report of non-24-h sleep-wake disorder with excessive daytime sleepiness

ABSTRACT

Myotonic dystrophy (MD) is a neuromuscular disease with myotonia, progressive weakness, and involvement of CNS, heart, and gastrointestinal system. Excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 (MD1) is related to sleep breathing diseases, restless leg syndrome, periodic limb movements during sleep and narcoleptic-like phenotype. However, authors highlight a central dysfunction of sleep regulation.

We describe a 26-year-old, female, MD1 patient with EDS. Sleep diary/actigraphy evidenced two different circadian periods with values of 1442 and 1522 min. Agomelatine, 50 mg at night, was prescribed with improvement of the circadian rhythm and complaints of sleepiness.

The identification of unanticipated causes of EDS, such as circadian rhythm disorders permits an appropriated treatment. As we know, it is the first relate of non-24-h sleep-wake disorder in patient with MD1. Sleep diary and actigraphy could be good options to investigate sleep-wake cycle disorder in patients with MD and EDS.     

Working Under Daylight Intensity Lamp: An Occupational Risk for Developing Circadian Rhythm Sleep Disorder?

A 47‐yr‐old male was admitted to the Institute for Fatigue and Sleep Medicine complaining of severe fatigue and daytime sleepiness. His medical history included diagnosis of depression and chronic fatigue syndrome. Antidepressant drugs failed to improve his condition. He described a gradual evolvement of an irregular sleep‐wake pattern within the past 20 yrs, causing marked distress and severe impairment of daily functioning. He had to change to a part‐time position 7 yrs ago, because he was unable to maintain a regular full‐time job schedule. A 10‐day actigraphic record revealed an irregular sleep-wake pattern with extensive day‐to‐day variability in sleep onset time and sleep duration, and a 36 h sampling of both melatonin level and oral temperature (12 samples, once every 3 h) showed abnormal patterns, with the melatonin peak around noon and oral temperature peak around dawn. Thus, the patient was diagnosed as suffering from irregular sleep‐wake pattern. Treatment with melatonin (5 mg, 2 h before bedtime) did not improve his condition. A further investigation of the patient's daily habits and environmental conditions revealed two important facts. First, his occupation required work under a daylight intensity lamp (professional diamond‐grading equipment of more than 8000 lux), and second, since the patient tended to work late, the exposure to bright light occurred mostly at night. To recover his circadian rhythmicity and stabilize his sleep‐wake pattern, we recommended combined treatment consisting of evening melatonin ingestion combined with morning (09:00 h) bright light therapy (0800 lux for 1 h) plus the avoidance of bright light in the evening. Another 10‐day actigraphic study done only 1 wk after initiating the combined treatment protocol revealed stabilization of the sleep‐wake pattern with advancement of sleep phase. In addition, the patient reported profound improvement in maintaining wakefulness during the day. This case study shows that chronic exposure to bright light at the wrong biological time, during the nighttime, may have serious effects on the circadian sleep‐wake patterns and circadian time structure. Therefore, night bright light exposure must be considered to be a risk factor of previously unrecognized occupational diseases of altered circadian time structure manifested as irregularity of the 24 h sleep‐wake cycle and melancholy.     

Ring the bell for Matins: circadian adaptation to split sleep by cloistered monks and nuns

Cloistered monks and nuns adhere to a 10-century-old strict schedule with a common zeitgeber of a night split by a 2- to 3-h-long Office (Matins). The authors evaluated how the circadian core body temperature rhythm and sleep adapt in cloistered monks and nuns in two monasteries. Five monks and five nuns following the split-sleep night schedule for 5 to 46 yrs without interruption and 10 controls underwent interviews, sleep scales, and physical examination and produced a week-long sleep diary and actigraphy, plus 48-h recordings of core body temperature. The circadian rhythm of temperature was described by partial Fourier time-series analysis (with 12- and 24-h harmonics). The temperature peak and trough values and clock times did not differ between groups. However, the temperature rhythm was biphasic in monks and nuns, with an early decrease at 19:39 ± 4:30 h (median ± 95% interval), plateau or rise of temperature at 22:35 ± 00:23 h (while asleep) lasting 296 ± 39 min, followed by a second decrease after the Matins Office, and a classical morning rise. Although they required alarm clocks to wake-up for Matins at midnight, the body temperature rise anticipated the nocturnal awakening by 85 ± 15 min. Compared to the controls, the monks and nuns had an earlier sleep onset (20:05 ± 00:59 h vs. 00:00 ± 00:54 h, median ± 95% confidence interval, p= .0001) and offset (06:27 ± 0:22 h, vs. 07:37 ± 0:33 h, p= .0001), as well as a shorter sleep time (6.5 ± 0.6 vs. 7.6 ± 0.7 h, p= .05). They reported difficulties with sleep latency, sleep duration, and daytime function, and more frequent hypnagogic hallucinations. In contrast to their daytime silence, they experienced conversations (and occasionally prayers) in dreams. The biphasic temperature profile in monks and nuns suggests the human clock adapts to and even anticipates nocturnal awakenings. It resembles the biphasic sleep and rhythm of healthy volunteers transferred to a short (10-h) photoperiod and provides a living glance into the sleep pattern of medieval time.     

Melatonin rhythms in delayed sleep phase syndrome

The aim of this study was to compare circadian and sleep characteristics between patients with delayed sleep phase syndrome (DSPS) and healthy controls. The authors studied 8 DSPS patients and 15 normal controls. Serum melatonin concentration was assessed every hour for 24 h under dim light conditions. The sleep phase and the melatonin rhythm in DSPS patients were significantly delayed compared to those in normal controls. Sleep length was significantly greater in DSPS patients compared to that in controls, but the duration of melatonin secretion did not differ between the two groups. The final awakening, relative to melatonin onset, melatonin midpoint, and melatonin offset, was significantly longer in DSPS patients than in controls. By contrast, the timing of sleep onset relative to melatonin rhythm did not differ between the two groups. The authors found a significant positive correlation between sleep phase markers and melatonin phase markers in DSPS. They postulate that a delayed circadian pacemaker may be responsible for delayed sleep phase syndrome. The alteration of phase angle between melatonin rhythm and sleep phase suggested that not only the delay of the circadian clock but also a functional disturbance of the sleep-wake mechanism underlies DSPS.     

The pattern of entrainment of the human sleep-wake rhythm by the natural photoperiod in the north

Recently, it was shown that the sleep-wake rhythm of the inhabitants of the temperate zone is entrained to sun time. In the North, significant seasonal changes in the photoperiod may interfere with entrainment of the circadian system to sunlight. This investigation assessed the influence of photoperiod characteristics on the sleep length and sleep-wake rhythm of residents of high latitude. The study was conducted in four towns and six villages located between 59.5?N and 67.6?N latitude between the months of October and May from 2009 through 2011 and included 2822 subjects aged 10 to 97 yrs, 1621 of whom were females and 1201 males. The chronotype and sleep length of the subjects were assessed using the Munich Chronotype Questionnaire. The instructions for the questionnaire stressed the need to specify the sleep-wake schedule during the week preceding the date of completing the questionnaire. The study found that the length of sleep and the chronotype of the inhabitants surveyed in Northern European Russia depend on age, sex, type of settlement, and place of residence. The time of sunrise was a stronger predictor of sleep length and chronotype than the time of sunset and day length. A later chronotype and shorter sleep length were found for the subjects during the equinox (sunrise at 06:00 h) than under long-photoperiod conditions (sunrise at 04:00-05:00 h). During short-photoperiod conditions (sunrise at 07:00-10:00 h), no significant changes in the self-reported sleep-wake rhythm were found. The time of sunrise had the strongest impact on the sleep-wake rhythm of 30- to 97-yr-old persons. Sunrise had a stronger influence on chronotype and sleep length in January to May, when the days become longer, than in October to December, when the days become shorter. Age- and season-associated changes were found in the entrainment of the sleep-wake rhythm by photoperiod in the North.     

An endogenous circadian rhythm in sleep inertia results in greatest cognitive impairment upon awakening during the biological night

Sleep inertia is the impaired cognitive performance immediately upon awakening, which decays over tens of minutes. This phenomenon has relevance to people who need to make important decisions soon after awakening, such as on-call emergency workers. Such awakenings can occur at varied times of day or night, so the objective of the study was to determine whether or not the magnitude of sleep inertia varies according to the phase of the endogenous circadian cycle. Twelve adults (mean, 24 years; 7 men) with no medical disorders other than mild asthma were studied. Following 2 baseline days and nights, subjects underwent a forced desynchrony protocol composed of seven 28-h sleep/wake cycles, while maintaining a sleep/wakefulness ratio of 1:2 throughout. Subjects were awakened by a standardized auditory stimulus 3 times each sleep period for sleep inertia assessments. The magnitude of sleep inertia was quantified as the change in cognitive performance (number of correct additions in a 2-min serial addition test) across the first 20 min of wakefulness. Circadian phase was estimated from core body temperature (fitted temperature minimum assigned 0 degrees ). Data were segregated according to: (1) circadian phase (60 degrees bins); (2) sleep stage; and (3) 3rd of the night after which awakenings occurred (i.e., tertiary 1, 2, or 3). To control for any effect of sleep stage, the circadian rhythm of sleep inertia was initially assessed following awakenings from Stage 2 (62% of awakening occurred from this stage; n = 110). This revealed a significant circadian rhythm in the sleep inertia of cognitive performance (p = 0.007), which was 3.6 times larger during the biological night (circadian bin 300 degrees , approximately 2300-0300 h in these subjects) than during the biological day (bin 180 degrees , approximately 1500-1900 h). The circadian rhythm in sleep inertia was still present when awakenings from all sleep stages were included (p = 0.004), and this rhythm could not be explained by changes in underlying sleep drive prior to awakening (changes in sleep efficiency across circadian phase or across the tertiaries), or by the proportion of the varied sleep stages prior to awakenings. This robust endogenous circadian rhythm in sleep inertia may have important implications for people who need to be alert soon after awakening.     

Effects of Light Interruption on Sleep and Viability of Drosophila melanogaster

Light is a very important regulator of the daily sleep rhythm. Here, we investigate the influence of nocturnal light stimulation on Drosophila sleep. Results showed that total daytime sleep was reduced due to a decrease in daytime sleep episode duration caused by discontinuous light stimulation, but sleep was not strongly impacted at nighttime although the discontinuous light stimulation occurred during the scotophase. During a subsequent recovery period without light interruption, the sleep quality of nighttime sleep was improved and of daytime sleep reduced, indicating flies have a persistent response to nocturnal light stimulation. Further studies showed that the discontinuous light stimulation damped the daily rhythm of a circadian light-sensitive protein cryptochrome both at the mRNA and protein levels, which subsequently caused disappearance of circadian rhythm of the core oscillator timeless and decrease of TIMLESS protein at nighttime. These data indicate that the nocturnal light interruption plays an important role in sleep through core proteins CRYTOCHROME and TIMLESS, Moreover, interruption of sleep further impacted reproduction and viability.     

Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans.

Biological circadian clocks oscillate with an approximately 24-hour period, are ubiquitous, and presumably confer a selective advantage by anticipating the transitions between day and night. The circadian rhythms of sleep, melatonin secretion and body core temperature are thought to be generated by the suprachiasmatic nucleus of the hypothalamus, the anatomic locus of the mammalian circadian clock. Autosomal semi-dominant mutations in rodents with fast or slow biological clocks (that is, short or long endogenous period lengths; tau) are associated with phase-advanced or delayed sleep-wake rhythms, respectively. These models predict the existence of familial human circadian rhythm variants but none of the human circadian rhythm disorders are known to have a familial tendency. Although a slight 'morning lark' tendency is common, individuals with a large and disabling sleep phase-advance are rare. This disorder, advanced sleep-phase syndrome, is characterized by very early sleep onset and offset; only two cases are reported in young adults. Here we describe three kindreds with a profound phase advance of the sleep-wake, melatonin and temperature rhythms associated with a very short tau. The trait segregates as an autosomal dominant with high penetrance. These kindreds represent a well-characterized familial circadian rhythm variant in humans and provide a unique opportunity for genetic analysis of human circadian physiology.     

月经周期对女性睡眠-觉醒和静息-活动的影响

目前有关月经周期对睡眠影响的研究结果并不一致,而对月经周期中昼夜睡眠-觉醒及静息-活动节律尚缺乏系统性的研究.本研究旨在观察正常育龄期女性月经周期中睡眠-觉醒及静息-活动昼夜节律的变化.我们采用静息-活动监测仪(actigraphy)和睡眠日志,调查了12个自然生活状态下健康育龄期妇女在月经周期不同阶段,即行经期、围排卵期、黄体早期及黄体晚期中睡眠与活动节律的变化.结果显示,睡眠-觉醒节律参数在四期之间无统计学显著差异;而静息-活动节律方面,所有受试女性静息-活动节律的平均日周期长度为(24.01±0.29)h,并且四期之间无显著性差异.行经期日间稳定系数(interdaily stability,IS)比黄体早期显著增加(P＜0.05).黄体早期日间活动开始时间明显较黄体晚期提前(P＜0.05);黄体早期的活动峰值时相比围排卵期显著提前(P＜0.05).月经周期可以影响静息-活动昼夜节律时相.而总体静息-活动数量与质量未发生显著变化;健康育龄期妇女在月经周期的各阶段中睡眠-觉醒节律亦无明显变异.