The Shape of the Endogenous Circadian Rhythm of Rectal Temperature in Humans

Fourteen healthy subjects have been studied in an isolation unit while living on a 30h “day” (20h awake, 10h asleep) for 14 (solar) days but while aware of real time. Waking activities were sedentary and included reading, watching television, and so forth. Throughout, regular recordings of rectal temperature were made, and in a subgroup of 6 subjects, activity was measured by a wrist accelerometer. Temperature data have been subjected to cosinor analysis after “purification,” a method that enables the endogenous (clock-driven) and exogenous (activity-driven) components of the circadian rhythm to be assessed. Moreover, the protocol enables effects due to the circadian rhythm and time-since-waking to be separated. Results showed that activity was slightly affected by the endogenous temperature rhythm. Also, the masking effects on body temperature exerted by the exogenous factors appeared to be less than average in the hours before and just after the peak of the endogenous temperature rhythm. This has the effect of producing a temperature plateau rather than a peak during the daytime. The implications of this for mental performance and sleep initiation are discussed. (Chronobiology International, 13(4), 261-271, 1996)     

Temperature Dependency of Circadian Period in a Single Cell (Acetabularia)

The circadian rhythm in the oxygen production of 30 individual Acetabularia cells has been studied at different temperatures. The temperature induced period variation was continuously evaluated over the whole data record of each individual cell with an advanced spectral analysis technique. The observed circadian periods of O₂ production displayed a well established region of temperature compensation between 25 °C and 30 °C with a Q₁₀, value of 0.9, whereas between 15°C and 22°C a positive temperature coefficient was measured (Q₁₀ at 22 °C 0.9, Q₁₀ at 20°C 0.8, Q₁₀at 17°C 0.7).     

Some Perturbations That Disturb the Circadian Melatonin Rhythm

The circadian melatonin rhythm is highly reproducible and generally not easily altered. The few perturbations that are capable of significantly changing either the amplitude or the pattern of the 24-h melatonin rhythm are summarized herein. Aging alters cyclic melatonin production by decreasing the amplitude of the nocturnal melatonin peak in all species in which it has been studied. The best known acute suppressor of nocturnal melatonin is light exposure. The brightness of light required to acutely depress pineal melatonin production is species dependent; of the visible wavelengths, those in the blue range (～500-520 nm) seem most effective in suppressing melatonin production. Nonvisible, nonionizing radiation in the extremely low frequency range (e.g., 60 Hz) seems also capable of altering pineal melatonin synthesis. Hormones have relatively little influence on the circadian production of melatonin, although either adrenalectomy or hypo-physectomy does attenuate the amplitude of the melatonin cycle. Exercise at the time of high melatonin production rapidly depresses pineal concentrations of the indole without influencing its synthesis; the mechanism of this suppression remains unknown.     

Some Perturbations That Disturb the Circadian Melatonin Rhythm

The circadian melatonin rhythm is highly reproducible and generally not easily altered. The few perturbations that are capable of significantly changing either the amplitude or the pattern of the 24-h melatonin rhythm are summarized herein. Aging alters cyclic melatonin production by decreasing the amplitude of the nocturnal melatonin peak in all species in which it has been studied. The best known acute suppressor of nocturnal melatonin is light exposure. The brightness of light required to acutely depress pineal melatonin production is species dependent; of the visible wavelengths, those in the blue range (∼500-520 nm) seem most effective in suppressing melatonin production. Nonvisible, nonionizing radiation in the extremely low frequency range (e.g., 60 Hz) seems also capable of altering pineal melatonin synthesis. Hormones have relatively little influence on the circadian production of melatonin, although either adrenalectomy or hypo-physectomy does attenuate the amplitude of the melatonin cycle. Exercise at the time of high melatonin production rapidly depresses pineal concentrations of the indole without influencing its synthesis; the mechanism of this suppression remains unknown.     

The Circadian Body Temperature Rhythm in the Elderly: Effect of Single Daily Melatonin Dosing

The present study is part of a more extensive investigation dedicated to the study and treatment of age‐dependent changes/disturbances in the circadian system in humans. It was performed in the Tyumen Elderly Veteran House and included 97 subjects of both genders, ranging from 63 to 91 yrs of age. They lived a self‐chosen sleep‐wake regimen to suit their personal convenience. The experiment lasted 3 wks. After 1 control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen?) daily at 22:30 h for 2 wks. The other 34 subjects were given placebo. Axillary temperature was measured using calibrated mercury thermometers at 03:00, 08:00, 11:00, 14:00, 17:00, and 23:00 h each of the first and third week. Specially trained personnel took the measurements, avoiding disturbing the sleep of the subjects. To evaluate age‐dependent changes, data obtained under similar conditions on 58 young adults (both genders, 17 to 39 yrs of age) were used. Rhythm characteristics were estimated by means of cosinor analyses, and intra‐ and inter‐individual variability by analysis of variance (ANOVA). In both age groups, the body temperature underwent daily changes. The MESOR (36.38±0.19°C vs. 36.17±0.21°C) and circadian amplitude (0.33±0.01°C vs. 0.26±0.01°C) were slightly decreased in the elderly compared to the young adult subjects (p<0.001). The mean circadian acrophase was similar in both age groups (17.19±1.66 vs. 16.93±3.08 h). However, the inter‐individual differences were higher in the older group, with individual values varying between 10:00 and 23:00 h. It was mainly this phase variability that caused a decrease in the inter‐daily rhythm stability and lower group amplitude. With melatonin treatment, the MESOR was lower by 0.1°C and the amplitude increased to 0.34±0.01°C, a similar value to that found in young adults. This was probably due to the increase of the inter‐daily rhythm stability. The mean acrophase did not change (16.93 vs. 16.75 h), although the inter‐individual variability decreased considerably. The corresponding standard deviations (SD) of the group acrophases were 3.08 and 1.51 h (p<0.01). A highly significant correlation between the acrophase before treatment and the phase change under melatonin treatment indicates that this is due to a synchronizing effect of melatonin. Apart from the difference in MESOR, the body temperature rhythm in the elderly subjects undergoing melatonin treatment was not significantly different from that of young adults. The data clearly show that age‐dependent changes mainly concern rhythm stability and synchronization with the 24 h day. A single daily melatonin dose stabilizes/synchronizes the body temperature rhythm, most probably via hypothermic and sleep‐improving effects.     

The Relation of Shift Work Tolerance to the Circadian Adjustment

The amplitude and phasing of circadian rhythms are under discussion as possible predictors of tolerance to night work. In a field study, subjective sleepiness and oral temperature of 147 female nurses were measured at 2-hour intervals during a period with one morning shift and two consecutive night shifts. The nurses also filled out a questionnaire. Two types of tolerance indices were constructed: The “health index” was based on questions referring to general fatigue, gastrointestinal symptoms, and sleep disturbances, and the “sleepiness index” on the actual subjective ratings of sleepiness. According to the health index, the group with good tolerance had a larger circadian amplitude of the oral temperature rhythm on the day of the morning shift than the group with poor tolerance. However, with regard to the sleepiness index, the corresponding difference between the groups with good or poor tolerance was not significant. The data did not confirm the hypothesis that predicts a quick adjustment of the circadian rhythm when the circadian amplitude is small before the change to night work. The contradictory results found in this and in other studies do not yet permit prediction of tolerance to night work.     

The Relation of Shift Work Tolerance to the Circadian Adjustment

The amplitude and phasing of circadian rhythms are under discussion as possible predictors of tolerance to night work. In a field study, subjective sleepiness and oral temperature of 147 female nurses were measured at 2-hour intervals during a period with one morning shift and two consecutive night shifts. The nurses also filled out a questionnaire. Two types of tolerance indices were constructed: The “health index” was based on questions referring to general fatigue, gastrointestinal symptoms, and sleep disturbances, and the “sleepiness index” on the actual subjective ratings of sleepiness. According to the health index, the group with good tolerance had a larger circadian amplitude of the oral temperature rhythm on the day of the morning shift than the group with poor tolerance. However, with regard to the sleepiness index, the corresponding difference between the groups with good or poor tolerance was not significant. The data did not confirm the hypothesis that predicts a quick adjustment of the circadian rhythm when the circadian amplitude is small before the change to night work. The contradictory results found in this and in other studies do not yet permit prediction of tolerance to night work.     

Circadian Rhythm in Pineal Methionine S-Adenosyltransferase

Abstract: The circadian rhythm of methionine S -adenosyltransferase, which catalyzes the formation of S -adenosylmethionine, a cosubstrate for melatonin in the pineal gland, follows the pattern of hydroxyindole- O -methyltransferase. Around the middle of the dark period, methionine S -adenosyltransferase and hydroxyindole- O -methyltransferase appear to be elevated by 2.5- and 1.5-fold, respectively, and tend to fall back during the light period.     

Circadian Rhythm in Plasma Noradrenaline of Healthy Sleep-Deprived Subjects

Under normal sleep-wake conditions, noradrenaline (NA) secretions in supine subjects exhibit a weak circadian variation with a peak that occurs around noon; the sleep span is characterized by reduced NA secretion. Some investigators have reported that the circadian NA rhythm is completely obliterated during sleep deprivation. In our laboratory, plasma NA was assayed every hour for 24 h in nine healthy men 20-23 years of age. All men were deprived of sleep and were required to eat and walk around every hour to prevent sleep. However, subjects remained supine for 20 min before blood samples were collected to eliminate the effect of activity. Persistence of a slight decrease in the night concentration in several subjects, despite sleep deprivation, suggests that NA secretion may be influenced by a biological clock whose activity becomes visible when the influence of posture is removed.     

The Circadian Rhythm of Plasma Thyrotropin in Depression and Recovery

The 24-hr patterns of plasma thyrotropin have been observed in 12 endogenous depressed patients in both depressed and recovered states and in 13 normal subjects. A clear circadian rhythm was detected in controls with high values at night. In depression, the circadian rhythm was altered with amplitude reduction and blunted nocturnal secretion, abnormalities particularly relevant in bipolar patients. This flattened profile could be linked to the blunted response of TSH to TRH administration reported in depressed patients. Normal nyctohemeral patterns have been restored after recovery. These chronobiological abnormalities as well as their normalization under antidepressant drugs seem to be similar to those reported for various parameters (e.g. temperature, Cortisol, etc) in depression which could support the chronobiological hypothesis for affective disorders.     

The Circadian Rhythm of Plasma Thyrotropin in Depression and Recovery

The 24-hr patterns of plasma thyrotropin have been observed in 12 endogenous depressed patients in both depressed and recovered states and in 13 normal subjects. A clear circadian rhythm was detected in controls with high values at night. In depression, the circadian rhythm was altered with amplitude reduction and blunted nocturnal secretion, abnormalities particularly relevant in bipolar patients. This flattened profile could be linked to the blunted response of TSH to TRH administration reported in depressed patients. Normal nyctohemeral patterns have been restored after recovery. These chronobiological abnormalities as well as their normalization under antidepressant drugs seem to be similar to those reported for various parameters (e.g. temperature, Cortisol, etc) in depression which could support the chronobiological hypothesis for affective disorders.     

Timekeeping Through Social Contacts: Social Synchronization of Circadian Locomotor Activity Rhythm in the Carpenter Ant Camponotus paria

In ant colonies a large proportion of individuals remain inside nests for most of their lives and come out only when necessary. It is not clear how, in a nest of several thousand individuals, information about local time is communicated among members of the colony. Central to this seem to be circadian clocks, which have an intrinsic ability to keep track of local time by entraining to environmental light-dark, temperature, and social cycles. Here, the authors report the results of their study aimed at understanding the role of cyclic social interactions in circadian timekeeping of a day-active species of carpenter ant Camponotus paria. The authors found that daily social interactions with visitors (worker ants) was able to synchronize the circadian locomotor activity rhythm of host worker ants and queens, in one-on-one (pair-wise) and multi-individual (group-wise) interactions. Interestingly, the outcome of cyclic social interactions was context specific; when visitor workers socially interacted with host workers one-on-one, host workers considered the time of interaction as subjective day, but when visitor workers interacted with a group of workers and queens, the hosts considered the time of interaction as subjective night. These results can be taken to suggest that members of the ant species C. paria keep track of local time by socially interacting with workers (foragers) who shuttle in and out of the colony in search of food. (Author correspondence: vsharma@jncasr.ac.in)     

生理节律与日常活动对人体疲劳程度的影响

目的:研究生理节律和日常活动分别对人体疲劳程度的影响大小。方法:选取某校7名大学生志愿者,在军训期间对每日军训科目严格限制条件下进行该实验,以闪光临界融合频率、心率变异性、反应时、静态姿势图TLX-NASA量表评分作为指标,对每天分别在训练前和训练后疲劳程度的大小进行测量,以这些指标描述训练前后的疲劳程度。结果:反应时降低(0.60±0.09)、反应正确率提高(0.97±0.03);闪光临界光融合频率升高(40.84±2.14);心率变异性TP(3076.60±382.08)降低、心率变异性SDNN(55.28±16.85)降低;静态姿势图晃动减少,中低频率段(0.15±0.01)、前后方向重心变位(7.92±0.63),TLX-NASA量表评分降低(30.47±10.23)。以上差异均具有统计学意义(P<0.05)。结论:生理节律相对于日常活动对机体的疲劳状态有更大的影响。     

动物内源褪黑素调控生物节律的研究进展

内源褪黑素对人类和其他哺乳动物的节律行为具有调控功能。生物节律是自然进化赋予生命的基本特征之一,生物体的生命活动受到生物节律的控制与影响。在哺乳动物中,节律调控中心是松果体,其主要功能是合成和分泌褪黑素。褪黑素广泛参与生物体节律行为的调节,本文从褪黑素的产生和作用机制,分别阐述褪黑素对昼夜节律行为和多种年节律行为的调控作用,同时明确褪黑素与生物钟及神经内分泌系统的直接作用和反馈互动的复杂集合,进一步揭示褪黑素调控生物节律的重要作用,以期为褪黑素的基础研究以及未来探究生物体的生物钟内源性发生机制提供参考。     

血压昼夜节律特征及其分子调控机制

正常血压具有典型的昼夜节律特征。血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系,是独立于血压水平的重要致病因素。血压昼夜节律的产生和维持与时钟基因的周期性表达有关。时钟基因bmal1、per2是体内生物钟系统运行的关键基因,其表达水平和节律变化直接调节血压的昼夜节律。     

Identification of an Annexin-Like Protein and Its Possible Role in the Aplysia Eye Circadian System

Abstract: Light and serotonin regulate the phase of the circadian rhythm of the isolated eye of Aplysia . To screen for possible protein components of the eye circadian oscillator, we identified a number of proteins whose synthesis was altered in opposite ways by light and serotonin. The cellular function of one of these proteins was investigated by obtaining a partial amino acid sequence of it and by examining its immunoreactivity. A 38-amino acid sequence was obtained from a 40-kDa (isoelectric point 5.6) protein. A greater than 60% amino acid identity existed between this sequence and sequences of a family of calcium/phospholipid-binding proteins called annexins. Furthermore, the 40-kDa protein reacted with antibodies generated against a conserved amino acid sequence of annexins and with antibodies raised against human annexin I. The identification of the 40-kDa, light- and serotonin-regulated protein as an annexin led us to hypothesize that arachidonic acid metabolism plays a role in the Aplysia eye circadian system. To test this hypothesis, we examined the ability of an inhibitor of the arachidonic acid metabolic pathway to perturb the eye rhythm. Pulse treatments of isolated eyes with a lipoxygenase inhibitor, nordihydroguaiaretic acid, phase shifted the rhythm. The phase-shifting ability of nordihydroguaiaretic acid suggests that arachidonic acid and some of its metabolites may play a role in the eye circadian system. The results of our studies raise the possibility that links may exist between the 40-kDa annexin-like protein, arachidonic acid metabolism, and the circadian oscillator.     

血压昼夜节律特征及其分子调控机制

正常血压具有典型的昼夜节律特征。血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系,是独立于血压水平的重要致病因素。血压昼夜节律的产生和维持与时钟基因的周期性表达有关。时钟基因bmal1、per2是体内生物钟系统运行的关键基因,其表达水平和节律变化直接调节血压的昼夜节律。     

Circadian Rhythm of Total Protein Synthesis in the Cytoplasm and Chloroplasts of Gonyaulaxpolyedra

Protein synthesis of Gonyaulax polyedra was analyzed by means of electron microscopic autoradiographs under constant conditions at different times of the 24-hr cycle. Circadian rhythmic changes in the synthesis rate of total protein were determined in the cytoplasm and chloroplasts of growing cells. Three independent series of experiments in constant light showed a maximum of grains per unit area during the 'subjective' dark phase (=phase that corresponds to the dark phase during a 12:12 hr LD cycle) in both compartments. Minimum and maximum grain number are different by a factor of 5-10. The maximum of total protein synthesis coincided with the maximum phase shift by cycloheximide pulses (1) suggesting protein species within the total pool involved in the mechanism of the circadian clock. A similar rhythm of lower amplitude was observed in the mitochondria, but this rhythm cannot with certainty be attributed to these organelles. In a slowly growing culture a rhythm of total protein synthesis was observed that showed a smaller amplitude and a different phasing.     

Reliability of the Circadian Rhythm of Water and Macronutrient-Rich Diets Intake in Dietary Choice

Rats with ad libitum water and the ability to self-select among three macronutrient-rich diets—carbohydrate (CHO), protein (PRO), and lipid (LIP)—show a circadian rhythmicity in their ingestion. The aim of the present study was to determine whether this circadian rhythmicity is reliable from day to day. Eight rats were offered ad libitum water and a choice of three isoenergetic diet rations providing carbohydrate, protein, and lipid. Water and food intake was recorded every 3 h for 7 days. The reliability of the circadian rhythm of water and food intake was assessed by the Intraclass Correlation Coefficient (ICC) and the test-retest reliability using the Pearson's Correlation Coefficient (r). The results showed that the circadian rhythm of water, CHO, and PRO intake are strongly reliable. However, the circadian rhythm of LIP intake is less reproducible. Among the three reliable parameters—water, CHO, and PRO, the circadian rhythm of water intake was the most reproducible over 7 days. This suggests that water intake may be used as a marker of circadian rhythmicity in ingestive behavior.