Circadian Temperature and Activity Rhythms in Mice under Free-Running and Entrained Conditions; Assessment after Purification of the Temperature Rhythm

Six female mice were studied separately for six weeks, first in constant light (300 lx), and then on a 12 : 12 L : D schedule (light on 07:00–19:00–h). Food and water were available ad libitum. Abdominal temperature and spontaneous locomotor activity were measured every 10 min. In constant light, the animals free-ran with both temperature and activity records showing circadian rhythms that were significantly greater than 24 h; by contrast, in the LD schedule, the circadian rhythms had become entrained and showed a stable phase relation to this schedule. The direct masking effects upon raw temperatures caused by bursts of activity were clearly seen, and could be removed by a process of ‘purification’. A comparison of the activity profiles during the entrained and free-running phases showed that the imposed light-dark cycle resulted in decreased activity in the light, increased activity in the dark, and bursts of activity at the light-dark and dark-light transitions. Masking effects due to the activity profile were present in the raw temperature profile, and many could be removed by purification using the activity profile; however, there was evidence that other masking effects, independent of activity, were present also. The efficacy of thermoregulatory compensation, as assessed from the rise of core temperature produced by spontaneous locomotor activity, was, in comparison with the free-running condition, increased in the dark phase and decreased in the light phase; this would appear to be one way to limit the temperature rise that occurs in the active phase of the rest-activity cycle.     

Effects of Pregnancy and Parturition on Free-Running Circadian Activity Rhythms in the Rat

Alterations in circadian rhythms have previously been associated with estrous and seasonal changes in reproductive state. In the present study we explored the effects of the reproductive events of pregnancy and parturition on free-running circadian activity rhythms in the rat. Free-running rhythms were monitored before mating, during pregnancy, and following parturition and removal of pups. Systematic and long-lasting alterations of the period of the free-running activity rhythm were seen following parturition. The effects of estrous, seasonal, and gestational reproductive states on circadian rhythms may be mediated by the endocrine events which accompany these states.     

Effects of Pregnancy and Parturition on Free-Running Circadian Activity Rhythms in the Rat

Alterations in circadian rhythms have previously been associated with estrous and seasonal changes in reproductive state. In the present study we explored the effects of the reproductive events of pregnancy and parturition on free-running circadian activity rhythms in the rat. Free-running rhythms were monitored before mating, during pregnancy, and following parturition and removal of pups. Systematic and long-lasting alterations of the period of the free-running activity rhythm were seen following parturition. The effects of estrous, seasonal, and gestational reproductive states on circadian rhythms may be mediated by the endocrine events which accompany these states.     

Plasticity of Circadian Activity and Body Temperature Rhythms in Golden Spiny Mice

Most animals can be categorized as nocturnal, diurnal, or crepuscular. However, rhythms can be quite plastic in some species and vary from one individual to another within a species. In the golden spiny mouse (Acomys russatus), a variety of rhythm patterns have been seen, and these patterns can change considerably as animals are transferred from the field into the laboratory. We previously suggested that these animals may have a circadian time‐keeping system that is fundamentally nocturnal and that diurnal patterns seen in their natural habitat reflect mechanisms operating outside of the basic circadian time‐keeping system (i.e., masking). In the current study, we further characterized plasticity evident in the daily rhythms of golden spiny mice by measuring effects of lighting conditions and access to a running wheel on rhythms in general activity (GA) and body temperature (Tb). Before the wheel was introduced, most animals were active mainly during the night, though there was considerable inter‐individual variability and patterns were quite plastic. The introduction of the wheel caused an increase in the level of nighttime activity and Tb in most individuals. The periods of the rhythms in constant darkness (DD) were very similar, and even slightly longer in this study (24.1±0.2 h) than in an earlier one in which animals had not been provided with running wheels. We found no correlation between the distance animals ran in their wheels and the period of their rhythms in DD. Re‐entrainment after phase delays of the LD cycle occurred more rapidly in the presence than absence of the running wheel. The characteristics of the rhythms of golden spiny mice seen in this study may be the product of natural selection favoring plasticity of the circadian system, perhaps reflecting what can happen during an evolutionary transition as animals move from a nocturnal to a diurnal niche.     

The Circadian Activity and Body Temperature Rhythms of Mice During Their Last Days of Life

Motor activity and body temperature rhythms have been investigated telemetrically in old mice until their death. The present paper is based mainly on the data of two animals which could be monitored over a sufficient length of time (more than three weeks), though the other three animals showed similar results. The daily body temperature rhythm of old mice was more stable as compared to the activity rhythm and was detectable until the last day of life. Its magnitude, defined as the difference between maximum and minimum, was similar to that obtained in middle-aged mice. By contrast, the activity rhythm disappeared or started to become erratic earlier. Unlike the position in younger animals, the body temperature rhythm was phase delayed with respect to the activity rhythm. In one mouse, the increased instability of the phase position two weeks before its death led to a free run with a period length of about 23.7 h. Both activity and temperature rhythms were fragmented in old mice. In the case of the body temperature this was obviously caused by masking. After purifying the raw temperatures, the fragmentation disappeared. On the other hand, the free-run condition was not caused by masking. The sensitivity of body temperature to motor activity was different from younger mice, and this probably reflects changes/deteriorations in the physiology of thermoregulation during the last days of life. In one mouse, during the last 4 days of life, a sharp, torpor-like decrease of body temperature corresponding with the time of the daily minimum was observed. This phenomenon was not found in other mice, though all of them died during the falling period of the temperature rhythm. The results confirm our hypothesis that the endogenous clock may work even during the very last days of life. The ability to synchronize with the periodic environment deteriorates earlier. Also they suggest that these phenomena are not only typical for the activity rhythm but apply also to the body temperature rhythm.     

The Circadian Activity and Body Temperature Rhythms of Mice During Their Last Days of Life

Motor activity and body temperature rhythms have been investigated telemetrically in old mice until their death. The present paper is based mainly on the data of two animals which could be monitored over a sufficient length of time (more than three weeks), though the other three animals showed similar results. The daily body temperature rhythm of old mice was more stable as compared to the activity rhythm and was detectable until the last day of life. Its magnitude, defined as the difference between maximum and minimum, was similar to that obtained in middle-aged mice. By contrast, the activity rhythm disappeared or started to become erratic earlier. Unlike the position in younger animals, the body temperature rhythm was phase delayed with respect to the activity rhythm. In one mouse, the increased instability of the phase position two weeks before its death led to a free run with a period length of about 23.7 h. Both activity and temperature rhythms were fragmented in old mice. In the case of the body temperature this was obviously caused by masking. After purifying the raw temperatures, the fragmentation disappeared. On the other hand, the free-run condition was not caused by masking. The sensitivity of body temperature to motor activity was different from younger mice, and this probably reflects changes/deteriorations in the physiology of thermoregulation during the last days of life. In one mouse, during the last 4 days of life, a sharp, torpor-like decrease of body temperature corresponding with the time of the daily minimum was observed. This phenomenon was not found in other mice, though all of them died during the falling period of the temperature rhythm. The results confirm our hypothesis that the endogenous clock may work even during the very last days of life. The ability to synchronize with the periodic environment deteriorates earlier. Also they suggest that these phenomena are not only typical for the activity rhythm but apply also to the body temperature rhythm.     

The Effect of Old Age on the Free-Running Period of Circadian Rhythms in Rat

The free-running period is regarded to be an exclusive feature of the endogenous circadian clock. Changes during aging in the free-running period may therefore reflect age-related changes in the internal organization of this clock. However, the literature on alterations in the free-running period in aging is not unequivocal. In the present study, with various confounding factors kept to a minimum, it was found that the free-running periods for active wakefulness, body temperature, and drinking behavior were significantly shorter (by 12-17 min) in old than in young rats. In addition, it was found that the day-to-day stability of the different sleep states was reduced in old rats, whereas that of the drinking rhythm was enhanced. Transient cycles were not observed, nor were there any age-related differences in daily totals of the various sleep-wake states. The amplitudes of the circadian rhythms of active wakefulness, quiet sleep, and temperature were reduced, whereas those of paradoxical sleep and quiet wakefulness remained unchanged.     

Circadian Activity Rhythms of Laboratory Mice during the Last Weeks of their Life

The aim of the present paper was a detailed analysis of changes of circadian activity rhythms immediately before natural death. Investigations were carried out on individually housed female laboratory mice. Locomotor activity was measured by passive infrared detectors starting with an age of about 75 weeks up to death. At the beginning all animals had pronounced circadian activity rhythms with a main maximum during the dark time and a secondary one just after light-on. As compared to adult mice the amount of activity and the circadian range of oscillation were lower. The main maximum was phase advanced in most of the animals, so that the percentage of activity during dark time accounted for less than 50% of the total 24-h activity. Towards death the amount of activity and the amplitude decreased even more. A circadian rhythm was preserved however as long as the animals were active, although its synchronization with LD-Zeitgeber deteriorated markedly. The phase position of the main maximum became more unstable, leading in some cases to complete uncoupling (free-run with t < 24 h). The secondary maximum in contrast was more stable in its phase and remained synchronized longer. The results show that in old age the mechanisms of synchronization break down earlier than the circadian rhythms. Therefore it seems possible to stabilize the circadian rhythms, e.g. by strengthening of Zeitgebers, which in turn may improve wellbeing and performance.     

Ultradian Rhythm of Activity in Japanese Quail Groups under Semi-Natural Conditions during Ontogeny: Functional Aspects and Relation to Circadian Rhythm

The function of ultradian rhythms is not yet clearly elucidated. In particular, short-term rhythms are expressed during early ontogeny, especially in broods of precocial birds. We investigated the relationship between the clarity of the ultradian rhythm of the activity/rest cycle of a group of young Japanese quail (Coturnix japonica) and the level of social synchronisation and spatial cohesion between the birds within that group. The subjects were descended from two lines selected for either very pronounced rhythmic or arrhythmic circadian activity. We found a positive relationship between the clarity of the ultradian rhythm of the activity/rest cycle when birds were young and the clarity of the circadian rhythm of feeding activity when birds were older, but still immature. The temporal organisation of the behaviour of the chicks from these two lines was observed in outdoor aviaries, when they were 4, 8, 12 and 15 days old. The mean ultradian period expressed by groups of 12 chicks was variable, with a minimum of 6 minutes. The ultradian period lengthened regularly as chicks grew older, and reached approximately 40 min on day 15. The clarity of the ultradian rhythmicity of group activity was linked to the level of inter-individual social synchronisation and of spatial cohesion; the more pronounced the ultradian rhythms of a group, the greater the temporal and spatial cohesion of the chicks within the group. Moreover, these characteristics varied with the age of the chicks. Finally, chicks in the less rhythmic groups weighed less. These results stress the adaptive value of this temporal organisation strategy under natural conditions.     

Circadian Rhythms of Enzymes' Activity in Mice Tissues During Exposure to Continuous Illumination

Activity rhythms of enzymes were determined in various tissues of C57BL/6J male mice. The determinations were carried out on mice which were kept in 14 hr light: 10 hr dark regimen, and on day 2, day 5 and day 21 during exposure to continuous illumination. Locomotor activity rhythms were followed in light: dark and up to the seventh day in constant light. All the activities exhibited a significant circadian rhythm in the light: dark regimen. During the exposure to continuous illumination, the locomotor activity exhibit a free running circadian rhythm with a consistent 24 hr and 40 min, major period component. At the same time recording the rhythms of enzyme activity; enzymes exhibited various formats of response which differed from those of the locomotor activity. The results suggest that rhythms of enzyme activity, as well as the desynchronization of the rhythms, are not enzyme specific.     

Assessment of Circadian Rhythms of Both Skin Temperature and Motor Activity in Infants During the First 6 Months of Life

The authors developed a method useful for home measurement of temperature, activity, and sleep rhythms in infants under normal-living conditions during their first 6 mos of life. In addition, parametric and nonparametric tests for assessing circadian system maturation in these infants were compared. Anthropometric parameters plus ankle skin temperature and activity were evaluated in 10 infants by means of two data loggers, Termochron iButton (DS1291H, Maxim Integrated Products, Sunnyvale, CA) for temperature and HOBO Pendant G (Hobo Pendant G Acceleration, UA-004-64, Onset Computer Corporation, Bourne, MA) for motor activity, located in special baby socks specifically designed for the study. Skin temperature and motor activity were recorded over 3 consecutive days at 15 days, 1, 3, and 6 mos of age. Circadian rhythms of skin temperature and motor activity appeared at 3 mos in most babies. Mean skin temperature decreased significantly by 3 mos of life relative to previous measurements (p?=?.0001), whereas mean activity continued to increase during the first 6 mos. For most of the parameters analyzed, statistically significant changes occurred at 3–6 mos relative to 0.5–1 mo of age. Major differences were found using nonparametric tests. Intradaily variability in motor activity decreased significantly at 6 mos of age relative to previous measurements, and followed a similar trend for temperature; interdaily stability increased significantly at 6 mos of age relative to previous measurements for both variables; relative amplitude increased significantly at 6 mos for temperature and at 3 mos for activity, both with respect to previous measurements. A high degree of correlation was found between chronobiological parametric and nonparametric tests for mean and mesor and also for relative amplitude versus the cosinor-derived amplitude. However, the correlation between parametric and nonparametric equivalent indices (acrophase and midpoint of M5, interdaily stability and Rayleigh test, or intradaily variability and P₁/P_ultradian) despite being significant, was lower for both temperature and activity. The circadian function index (CFI index), based on the integrated variable temperature-activity, increased gradually with age and was statistically significant at 6 mos of age. At 6 mos, 90% of the infants' rest period coincided with the standard sleep period of their parents, defined from 23:00 to 07:00?h (dichotomic index I?<?O; when I?<?O?=?100%, there is a complete coincidence between infant nocturnal rest period and the standard rest period), whereas at 15 days of life the coincidence was only 75%. The combination of thermometry and actimetry using data loggers placed in infants' socks is a reliable method for assessing both variables and also sleep rhythms in infants under ambulatory conditions, with minimal disturbance. Using this methodological approach, circadian rhythms of skin temperature and motor activity appeared by 3 mos in most babies. Nonparametric tests provided more reliable information than cosinor analysis for circadian rhythm assessment in infants. (Author correspondence: elvirada@um.es)     

Ultradian Rhythm of Activity in Japanese Quail Groups under Semi-Natural Conditions during Ontogeny: Functional Aspects and Relation to Circadian Rhythm

The function of ultradian rhythms is not yet clearly elucidated. In particular, short-term rhythms are expressed during early ontogeny, especially in broods of precocial birds. We investigated the relationship between the clarity of the ultradian rhythm of the activity/rest cycle of a group of young Japanese quail (Coturnix japonica) and the level of social synchronisation and spatial cohesion between the birds within that group. The subjects were descended from two lines selected for either very pronounced rhythmic or arrhythmic circadian activity. We found a positive relationship between the clarity of the ultradian rhythm of the activity/rest cycle when birds were young and the clarity of the circadian rhythm of feeding activity when birds were older, but still immature. The temporal organisation of the behaviour of the chicks from these two lines was observed in outdoor aviaries, when they were 4, 8, 12 and 15 days old. The mean ultradian period expressed by groups of 12 chicks was variable, with a minimum of 6 minutes. The ultradian period lengthened regularly as chicks grew older, and reached approximately 40 min on day 15. The clarity of the ultradian rhythmicity of group activity was linked to the level of inter-individual social synchronisation and of spatial cohesion; the more pronounced the ultradian rhythms of a group, the greater the temporal and spatial cohesion of the chicks within the group. Moreover, these characteristics varied with the age of the chicks. Finally, chicks in the less rhythmic groups weighed less. These results stress the adaptive value of this temporal organisation strategy under natural conditions.     

Circadian Rhythm of Irinotecan Tolerability in Mice

The toxicity of irinotecan (CPT-11), a topoisomerase-I inhibitor largely used in cancer patients, was investigated as a function of the circadian time of its administration in mice, with mortality, body weight loss, leukopenia, neutropenia, intestinal lesions, and bone marrow cell cycle phase distribution as end points. Four experiments were performed on a total of 773 male mice standardized with 12 h light/12 h darkness. Irinotecan was administered daily for 4 or 10 consecutive days (D1-4 and D1-10, respectively, in different experiments) at one of six circadian stages expressed in hours after light onset (HALO). The survival curves differed significantly as a function of the dosage and circadian time of drug administration by the D1-10 schedule, with 70% survival at 7 or 11 HALO and 51% at 19 or 23 HALO ( p = 0.039 from log rank test). CPT-11 administration at 19 or 23 HALO resulted in (1) greatest mean body weight loss at nadir; (2) most severe colic and bone marrow lesions and/or slowest recovery; and (3) deepest neutropenia nadir and/or slowest hematologic recovery. These circadian treatment time-related differences were statistically validated. The bone marrow cell cycle data revealed a four to eight-fold larger G2-M phase arrest following irinotecan administration at 19 or 23 HALO in comparison to the other times of drug administration, apparently representative of the repair of more extensive DNA damage ( p < 0.001 from ANOVA) when the medication was given at these circadian times. Overall, CPT-11 was better tolerated by mice treated during the light (animals’ rest) span. The results support the administration of CPT-11 to cancer patients in the second half of the night, during sleep, in order to improve drug tolerability.     

Relationship Between Infant and Mother Circadian Rest-Activity Rhythm Pre- and Postpartum,in Comparison to an Infant With Free-Running Rhythm

Some infants show a free-running rhythm in their rest-activity. We do not know why, nor do we know exactly what the entrainment factors are for the development of the normal 24-h rest-activity rhythm. Actigraphic recordings on 10 primiparae during late pregnancy and these mothers and their infants during the 2nd, 6th, and 12th wks after birth were made over 3–5 continuous days to investigate maternal and infant entrainment. One infant showed a free-running rest-activity circadian rhythm. In late pregnancy, the period in the autocorrelogram of the mother with the free-running infant was longer than the significant period of the mean autocorrelogram of the mothers with non-free-running infants. The finding of this study indicates the free-running rhythm of infant is not reset by maternal entrainment factors. (Author correspondence: nishihara-kk@igakuken.or.jp)     

光周期对棕色田鼠和昆明小鼠昼夜节律及活动的影响

光周期对动物昼夜节律的维持具有重要的影响,地下鼠的生活方式导致其昼夜活动节律产生变化,分化出随机活动和节律型两种模式.本文采用录像观察记录的方法,测定了棕色田鼠(Lasioposomys mandarinus)和昆明小鼠(Mus musculus)在不同光暗周期下的昼夜节律变化.结果表明:28 d的光周期变化对棕色田鼠...     

Circadian Rhythms in Photosynthesis : Oscillations in Carbon Assimilation and Stomatal Conductance under Constant Conditions

Net carbon assimilation and stomatal conductance to water vapor oscillated repeatedly in red kidney bean, Phaseolus vulgaris L., plants transferred from a natural photoperiod to constant light. In a gas exchange system with automatic regulation of selected environmental and physiological variables, assimilation and conductance oscillated with a free-running period of approximately 24.5 hours. The rhythms in carbon assimilation and stomatal conductance were closely coupled and persisted for more than a week under constant conditions. A rhythm in assimilation occurred when either ambient or intercellular CO₂ partial pressure was held constant, demonstrating that the rhythm in assimilation was not entirely the result of stomatal effects on CO₂ diffusion. Rhythms in assimilation and conductance were not expressed in plants grown under constant light at a constant temperature, demonstrating that the rhythms did not occur spontaneously but were induced by an external stimulus. In plants grown under constant light with a temperature cycle, a rhythm was entrained in stomatal conductance but not in carbon assimilation, indicating that the oscillators driving the rhythms differed in their sensitivity to environmental stimuli.     

Alterations of Circadian Rhythms in Mice Induced by Anti-Cancer Drugs

Carboplatinum was injected into four groups of mice for 5 successive days at one out of four daily equidistant hours. Upon the cessation of these injections, granulocyte colony stimulating factor was injected into half of these mice for 2 days at the same times. The stimulating factor was also injected into groups of untreated mice for 2 days at the same times. In each experiment the rhythms of four variables were monitored after the cessation of all injections: peripheral WBC count, bone marrow and sperm stem cells DNA synthesis, and sperm ribosomal RNA content. The results indicated that in the course of repeated drug administrations, variables' rhythm parameters (phases and periods) were altered. These changes have to be considered in chronotherapeutic schedules when variables which serve for toxicity diagnosis or as drug target are rhythmic in nature.     

Zebrafish Temperature Selection and Synchronization of Locomotor Activity Circadian Rhythm to Ahemeral Cycles of Light and Temperature

In addition to light cycles, temperature cycles are among the most important synchronizers in nature. Indeed, both clock gene expression and circadian activity rhythms entrain to thermocycles. This study aimed to extend our knowledge of the relative strength of light and temperature as zeitgebers for zebrafish locomotor activity rhythms. When the capacity of a 24∶20°C (thermophase∶cryophase, referred to as TC) thermocycle to synchronize activity rhythms under LL was evaluated, it was found that most groups (78%) synchronized to these conditions. Under LD, when zebrafish were allowed to select the water temperature (24°C vs. 20°C), most fish selected the higher temperature and showed diurnal activity, while a small (25%) percentage of fish that preferred the lower temperature displayed nocturnal activity. Under conflicting LD and TC cycles, fish showed diurnal activity when the zeitgebers were in phase or in antiphase, with a high percentage of activity displayed around dawn and dusk (22% and 34% of the total activity for LD/TC and LD/CT, respectively). Finally, to test the relative strength of each zeitgeber, fish were subjected to ahemeral cycles of light (T=25 h) and temperature (T=23 h). Zebrafish synchronized mostly to the light cycle, although they displayed relative coordination, as their locomotor activity increased when light and thermophase coincided. These findings show that although light is a stronger synchronizer than temperature, TC cycles alone can entrain circadian rhythms and interfere in their light synchronization, suggesting the existence of both light‐ and temperature‐entrainable oscillators that are weakly coupled.