Clear Circadian Pattern Research Articles

Ozone-induced paradoxical sleep decrease is related to diminished acetylcholine levels in the medial preoptic area in rats

Ozone (O 3) produces significant effects on sleep, characterized specially by a decrease in paradoxical sleep (PS) and increase in slow-wave sleep (SWS), which in turn represent a sleep-wake cycle disruption. On the other hand, neuronal activity recorded in the cholinoceptive hypothalamic medial preoptic area (MPO) has been involved in the regulation of sleep. However, there is no direct evidence on the role that acetylcholine (Ach) release in the MPO plays in the sleep-wake cycle. In order to study this relation, we measured the Ach concentration in dialysates collected from MPO in rats exposed to coal-filtered air (clean air) for 48 h and in rats exposed to clean air for 24 h followed by 24-h of O 3 exposure to 0.5 ppm. Polygraphic sleep records were taken simultaneously to neurochemical sampling. O 3 was employed to disrupt the sleep-wake cycle and relate these changes with concomitant disruptions in Ach concentration dialyzed from MPO. A clear circadian pattern of Ach concentration was observed in dialysates from MPO and also in PS, SWS and wakefulness of rats exposed to filtered air. However, O 3 exposure decreased the PS by 65% (Mann–Whitney's U-test, p ≤ 0.0003) and a concomitant decrease of extracellular Ach of 58% ( p ≤ 0.0239) was observed during the light phase. These changes were maintained during the dark phase, although it was also observed that slow-wave sleep increased by 75% ( p ≤ 0.0013) while wakefulness was decreased in 35% ( p ≤ 0.0007). We conclude that Ach release in MPO follows a circadian rhythm that is disrupted by O 3 exposure, and these changes are strongly associated with the O 3-induced PS disruptions.

Ritmo circadiano da taxa respiratória de Tetragonisca angustula fiebrigi (Schwarz), T. a. angustula (Latreille) e Trigona spinipes (Fabricius) (Hymenoptera, Apidae, Meliponinae)

Foi determinado em operárias isoladas de Tetragonisca angustula fiebrigi (Schwarz, 1938), T. a. angustula (Latreille, 1807) e Trigona spinipes (Fabricius, 1793) o ritmo circadiano das taxas respiratórias médias (VO2) em condições de ciclo normal (dia/claro e noite/escuro), durante a primavera. O consumo de oxigênio foi determinado a 30ºC usando um respirômetro de Warburg. A análise estatística dos resultados revelou interações significativas entre intervalos de tempo e entre as espécies. Foram comparadas as taxas respiratórias usando o teste do Tukey. Um padrão definido de ritmo circadiano metabólico foi observado para ambas as espécies, apresentando um maior consumo de oxigênio durante o dia, com um pico entre 10:00 e 15:00. À noite o consumo diminuiu, alcançando os níveis mínimos entre 2:00 e 3:00. Tetragonisca angustula angustula e T. a. fiebrigi não apresentaram diferenças significativas entre si, mas diferiram de T. spinipes, que apresentou taxas respiratórias maiores.

Light and circadian regulation in the expression of LHY and Lhcb genes in Phaseolus vulgaris.

In order to understand some aspects of the circadian clock function in Phaseolus vulgaris, we analyzed the temporal transcript profile of Lhcb genes, typical clock reporters in plants, and that of PvLHY, an orthologue of Arabidopsis thaliana LHY which is a putative transcription factor of Lhcb genes. Under different light regimes, Lhcb and PvLHY exhibit a clear circadian pattern of expression. Moreover, the rhythm of Lhcb genes appears to be tightly coupled to that of PvLHY with the latter having a slightly earlier phase. This supports the idea that the oscillating capacity of PvLHY may be one of the causes of the rhythmic expression of Lhcb genes in bean. In addition to their circadian regulation, Lhcb and PvLHY are induced by light with similar and relatively slow induction kinetics. Moreover, this light induction is gated by the circadian oscillator: minimal responses occur at times around peaks of the pre-existing rhythm, while maximal ones occur at troughs of the pre-existing rhythm. This pattern of gating is opposite to that observed in Arabidopsis. The failure to block the light induction pathways at pre-existing troughs appears to have a detrimental effect to the subsequent circadian rhythmicity. Briefly, the overall regulation of PvLHY and Lhcb genes by light and the circadian clock reveals different strategies between Phaseolus and Arabidopsis in the adaptation to photoperiodic conditions.

Normal Values and Determinants of Circadian Urine Production in Older Men: A Population Based Study

We evaluated circadian urine production and its determinants in a large population based sample of older men. We collected data on 1,688 men 50 to 78 years old, without radical prostatectomy, prostate or bladder cancer, neurogenic bladder disease or negative advice from their general practitioner, recruited from the population of Krimpen, the Netherlands. Measurements consisted of self-administered questionnaires, including the International Prostate Symptom Score, a 3-day frequency-volume chart, transrectal prostatic ultrasound, uroflowmetry and post-void residual volume. Hourly urine production was determined and urine production day-to-night ratio was calculated from the frequency-volume chart. Men younger than 65 years showed a clear circadian urine production pattern, whereas in older men this pattern was less clear. Smoking, use of diuretic drugs, post-void residual and 24-hour polyuria reinforced the circadian pattern, in favor of daytime urine production. The urine production day-to-night ratio was not associated with prostate enlargement, reduced urinary flow rate, body weight, hypertension, cardiac symptoms, diabetes mellitus, use of antidepressants, cardiac or hypnotic drugs. Urine production in men younger than 65 years showed a clear circadian pattern in contrast to men older than 65 years. These data can be used as a reference when describing urine production patterns in select populations. In daily practice frequency-volume charts can be used to determine urine production. This method is inexpensive, easy to use and provides valid information on urine production in a natural environment.

Restless legs syndrome: a sensorimotor disorder of sleep/wake motor regulation.

Restless legs syndrome (RLS) remains an underappreciated sensorimotor disorder of sleep/wake regulation. It is one of the few sensorimotor disorders that is provoked by rest and that also follows a clear circadian pattern. Recent epidemiologic studies have verified that the condition is common in populations derived from the north and west of Europe, and have begun to uncover some of the genetic substrate of the disorder. New instruments have been developed to facilitate diagnosis and assessment of severity. The pathogenesis of the condition remains uncertain, but recent discoveries implicate areas of the nervous system from the spinal cord up to the basal ganglia. A current hypothesis undergoing vigorous exploration is that the condition results from a deficiency of dopaminergic function based on abnormalities of iron transport and storage. Therapeutically, studies have shown the dopamine agonists to be the most reliable treatment for severe cases, whereas other recent studies have successfully utilized a number of other medications, including levodopa, opioids, and anticonvulsants. New standards provide guidelines for management of RLS and make specific pharmacotherapeutic recommendations.

Circadian rhythm of breath hydrogen in young women.

Breath hydrogen levels, which reflect colonic fermentation of undigested starches, are usually low in the fasted state. Fasting levels of breath hydrogen are important for estimation of oro-cecal transit time and diagnosis of lactase deficiency. In young women, however, fasting levels of breath hydrogen are high. To clarify the reason for this, we studied the circadian pattern of breath hydrogen and the effect of alpha-D-galactosidase on fasting breath hydrogen in one study, and the effect of sleep deprivation on fasting breath hydrogen in another study, in 13 women students aged 21-23 years. In the first study, two breath samples were collected, one in the evening and the other the next morning. On another occasion, alpha-D-galactosidase was given before dinner and breath samples were collected the next morning. In the second study, the circadian rhythm of breath hydrogen was assessed for 3 days and the subjects were deprived of sleep on the second night. Breath samples were collected every 30 min, except during the second night when samples were collected at 1-h intervals. Fasting breath hydrogen was 24 +/- 3.9 ppm (mean +/- SE), which did not differ from the value for the previous night. Alpha-D-galactosidase significantly decreased fasting breath hydrogen levels, to 17 +/- 2.4 ppm (P < 0.05). There was a clear circadian pattern of breath hydrogen, high in the morning and decreasing to the nadir by 16:00. After dinner, the level increased again and stayed high during the night. Sleep deprivation did not affect fasting levels of breath hydrogen. High fasting breath hydrogen levels in young women followed a circadian pattern and this may have been due, in part, to an high intake of dietary fiber on the previous day.

Pulsatile secretion of thyrotropin in children.

To examine pulsatile TSH secretion, serum TSH was determined every 30 min for 24 h in eight short normal prepubertal children (3 males and 5 females, age 4.0-12.6 yr). All children exhibited a clear circadian pattern of TSH secretion. Pulsatile TSH secretion was identified in all subjects with a mean (+/- SD) TSH pulse frequency of 6.9 +/- 1.2 pulses/24 h. The group mean TSH pulse amplitude was 1.4 +/- 0.3 mU/L. Mean TSH concentration was higher during the night hours (2.1 +/- 0.8 mU/L) than during the day hours (1.3 +/- 0.4 mU/L, p < 0.005), and significantly more pulses were detected during the night (mean 4.7 +/- 1.4) than during the day hours (2.1 +/- 0.6, p < 0.005). On average, 62 to 68% of the peaks were detected in the night hours. Mean TSH pulse amplitude during the night hours was not significantly different from that during the day hours. Our findings indicate that, as previously shown in adults, a pulsatile pattern of TSH secretion is present in children. In our study group, the nocturnal TSH surge is associated with an increase in pulse frequency but not amplitude.

Quality of life and circadian variation of heart rate and heart rate variability in short‐term survivors and nonsurvivors after acute myocardial infarction

The purpose of this study was the simultaneous examination of the quality of life and changes in heart rate (HR) variables of patients immediately following acute myocardial infarction (AMI). Quality of life, estimated on a rating scale assessing the patients' well-being, as well as the circadian rhythm of their HR and HR variability, were determined within the first 3 days and at approximately 3 weeks after admission and the results were related to survival. The quality of life within the first 3 days post AMI was low in both the surviving (n = 42) and the nonsurviving (n = 5) patients but only the scores of the survivors increased significantly over the following three weeks. The HR of the survivors, initially lower than that of the nonsurvivors, decreased significantly at 3 weeks and a normal circadian pattern had developed. The HR variability of the survivors within the first 3 days was significantly higher than that of the nonsurvivors and had developed a clear circadian pattern after 3 weeks. It is concluded that in patients with AMI such diverse clinical aspects as quality of life and circadian patterns of HR and HR variability can be assessed meaningfully immediately post AMI and may find common expression in changes in sympathovagal balance.

Use of breath hydrogen and methane as markers of colonic fermentation in epidemiologic studies: circadian patterns of excretion.

Fermentation in the large bowel has been postulated to play a protective role against colon cancer. Hydrogen and methane are end products of this fermentation process and are absorbed into the bloodstream and excreted via expired air in the breath. Breath levels of hydrogen and, to a lesser extent, methane correlate strongly with colonic fermentation and may serve as useful biomarkers for this process. In a preliminary study to assess the usefulness of these two markers in epidemiologic studies, we followed the hourly excretion of the two gases in expired alveolar air for 48 hr in 20 healthy subjects, using a Quintron gas chromatograph equipped with a solid-state detector specific for reducing gases. All subjects excreted hydrogen, but 71% did not excrete methane. Possible atmospheric contamination of the samples was corrected for on the basis of breath carbon dioxide levels. A clear circadian pattern of excretion was observed for breath hydrogen, with a decrease during the early morning followed by a progressive increase during the rest of the day. Methane excretion was constant throughout the day. This study shows that four samples collected at convenient times (0600, 1300, 1800, and 2200 hr) are optimal to characterize individuals by their breath excretions of hydrogen and methane during a 24-hr period.

Development of a Circadian Variation of Plasma Oxytocin Concentration in the Late Gestation Rhesus Monkey*

The 24-h pattern of oxytocin (OT) concentrations in maternal plasma was investigated serially from 112-168 days gestation in four chair-restrained pregnant rhesus monkeys. No change in the mean daily plasma OT concentration was observed with advancing gestational age; there was a change in the pattern of plasma OT secretion throughout the period, however. About 21 days from delivery (150.8 +/- 1.8 days gestational age), plasma OT levels showed occasional fluctuations, distributed throughout the day. About 8 days from delivery (163.2 +/- 2.4 days gestational age), a clear circadian pattern of OT was detected, with an acrophase at 2200 h. These results suggest that there is a relationship between the pattern of OT secretion and advancing pregnancy. This may account partially for the increase in uterine activity known to occur in term rhesus monkeys.

Selective dopamine D 1 and D 2 agonists independently affect different components of the free-running circadian rhythm of locomotor activity in rats

The effects of selective dopamine D 1 (SKF 38393) and D 2 (4-propyl-9-hydroxynaphthoxazine or PHNO) agonists on free-running rhythms of locomotor activity in rats were investigated under either constant light (LL) or dark (DD) condition. Rats under the DD condition exhibited clear circadian patterns of activity, while circadian patterns of activity in animals kept under the LL condition were more ambiguous. Under the DD condition, SKF 38393 significantly increased the length of the period of free-running rhythms of locomotor activity but had no effect on the amplitude and the mesor, while PHNO significantly increased the amplitude and the mesor of free-running rhythms but had no effect on the length of the period.

The Circadian Rhythm of Angina Pectoris

Analysis of diary card data from 33,999 angina attacks recorded in 1,022 patients with chronic stable angina showed a clear circadian pattern to the frequency of angina that resembles patterns previously described for myocardial infarction and sudden cardiac death, with a peak in the morning. The majority of angina attacks were preceded by physical exertion and the circadian pattern was more pronounced for exertional angina than nonexertional angina. In this study, treatment with beta-blockers did not prevent the morning peak of angina attacks.

Relations between depressed mood and vocal parameters before, during and after sleep deprivation: a circadian rhythm study

The mechanism underlying improvement after total sleep deprivation (TSD) was studied in 14 major depressed patients. The suggestions that (1) circadian processes and/or (2) dimensions of arousal may play a role in the response to TSD were investigated. Diurnal variation of depressed mood and of mood- and arousal-related vocal parameters was studied in relation to the effect of TSD on depressed mood and vocal parameters. During 3 baseline days, during TSD and 2 days after TSD vocal parameters and depressed mood were assessed 6 and 3 times daily respectively. The mean fundamental frequency (frequency of vocal fold vibration, F0) (presumably reflecting aspects of arousal) as well as the range of the F0 (proposed to reflect sadness) showed a clear circadian pattern with a peak at about 4.00 p.m. TSD affected the circadian organization of the mean F0 and advanced the peak of the curve. After one night of subsequent sleep this effect disappeared. In addition, improvement after TSD coincided with an increase of the mean F0. The diurnal variation of mood before TSD predicted the mood response to TSD, whereas diurnal variation of vocal parameters did not. Moreover, circadian changes in vocal parameters were not related to changes in depressed mood. These findings suggest that the diurnal variations in mood and vocal parameters are regulated by different mechanisms. Data support the presumption that circadian as well as arousal processes are involved in the mood response to TSD. Circadian changes in vocal parameters due to TSD are not likely to reflect changes in the biological clock.

Twenty-four-hour profiles of body temperature and plasma TSH in bipolar patients during depression and during remission and in normal control subjects.

The 24-hour patterns of body temperature and plasma thyrotropin (TSH) were measured in eight bipolar patients in both depressed and recovered (after 3 weeks of treatment) states and in eight normal control subjects. Clear circadian patterns were detected for both temperature and TSH. Nocturnal body temperature was increased and the nocturnal surge of TSH was blunted during depression; these abnormalities were corrected after recovery. The inverse relationship between changes in body temperature and TSH levels at night suggests that changes in thermoregulation may be responsible for the neuroendocrine disturbance and may play a role in the pathophysiology of depression.

Diurnal patterns in brain biogenic amines of rats exposed to 60-Hz electric fields.

Levels of brain neurotransmitters and their metabolites, as well as concentrations of enzymes associated with their synthesis and metabolism, fluctuate during the day in patterns defined as circadian. The present study examined these rhythms in albino rats exposed to 60-Hz electric fields. Thirty-six animals were exposed to a 39 kV/m field for 4 weeks, 20 h/day, in a parallel-plate electrode system. A group of 36 sham animals was similarly handled and housed in a nonenergized exposure system. On the sampling day, animals were sacrificed at 4-h intervals throughout the 24-h day. Brains were removed, dissected, and kept frozen until chemically analyzed. The levels of biogenic amines and their acidic metabolites in the striatum, hypothalamus, and hippocampus were determined by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) methods. Repeated exposure to 60-Hz electric fields produced significant alterations in the diurnal rhythms of several biogenic amines: dihydroxyphenylacetic acid (DOPAC, the primary metabolite of dopamine in the rat) in the striatum, and norepinephrine, dopamine, and 5-hydroxyindoleacetic acid (5-HIAA; serotonin metabolite) in the hypothalamus. Levels of serotonin in the striatum and hypothalamus showed clear circadian patterns that was not affected by the field. No diurnal or field-related changes were observed in the hippocampal amines.

Effects of adult or perinatal hormonal environment on ultradian rhythms in locomotor activity of laboratory LEW/Ztm rats

Four experiments were performed with male and female rats of the inbred strain LEW/Ztm maintained under a light-dark schedule of 12:12 hours. The animals were subject to castration (GOX) or ovariectomy (OVX), estradiol 17β-implantation (E2-capsules), and perinatal hormonal treatments with testosterone propionate (TP) and an androgen antagonist (cyproterone acetate, CA). Results indicated a difference in the locomotor activity pattern between the two sexes as a result of the endogenous estradiol levels of the adult animals. The activity pattern of male LEW rats was characterized by ultradian rhythms of 4 and 4.8 hr periods. The female LEW rats, on the other hand, generally exhibited a clear circadian activity pattern and no ultradian activity rhythms. Following ovariectomy, each of the females showed distinct ultradian rhythms. These disappeared after E2-implantation. Castration of adult males had no effect on the ultradian activity pattern. Implantation of E2-capsules resulted in a marked decrease of the ultradian activity components. Perinatal treatment of the males with an androgen antagonist (CA) did not appear to effect ultradian rhythms during adulthood. Females treated perinatally with testosterone showed a significant increase in the ultradian activity components. This effect is assumed to be due to low estrogen levels in these animals during adulthood. Our study supports the assumption that ultradian rhythms are a result of changes in the phase relationships between several circadian oscillators. The synchrony of these oscillations seems to be facilitated by estradiol.

An EEG averaging technique for automated sleep-wake stage identification in the rat

An automated on-line sleep-wake classification system based on an averaging technique of the running EEG is described. It operates for three rats simultaneously and is able to discriminate every 5 sec between wakefulness, light slow-wave sleep, deep slow-wave sleep, and paradoxical sleep. The hippocampal EEG and nuchal EMG are used as input parameters. The EEG is bandpass filtered after which a microcomputer samples and averages the filtered EEG and constructs spectrograms. The variability, the theta-delta ratio and the amplitude of the delta waves are obtained from these spectrograms. Together with the amplitude index of the EMG, these three EEG indices are subjected to decision rules for the identification of sleep-wake states. A first evaluation study showed 93% agreement between visual inspection and computer classification. In a second evaluation study 24-hr recordings were made. Clear circadian patterns emerged especially during the light period: deep slow-wave sleep was enhanced during the initial hours, while paradoxical sleep tended to increase over the latter hours. The outcome of these studies is compared with the results obtained with other automated sleep identification procedures.

Circadian variation of catecholamine excretion and sleep

Six male subjects were exposed to seven different bedtimes — one per week — scheduled in 4-h intervals. Sleep length was ad lib with spontaneous awakenings. The time awake varied between 16 and 40 h. The influence of overt time-of-day cues was minimized. Urine for analysis of catecholamines was collected in 2-h intervals during waking and for each of the sleep episodes. Sleep length varied strongly with the time of day, the longest sleep (8–11 h) occurring after evening bedtimes, and the shortest (4–5 h) after morning and noon bedtimes. Adrenaline excretion during waking showed a clear circadian pattern, peaking around noon, while no significant rhythm was found for noradrenaline excretion. The excretion of noradrenaline was strongly reduced by sleep, irrespective of the time of day. The circadian pattern of adrenaline during waking was abolished during sleep; sleep reduced excretion to the same low level irrespective of the time of day. In the early morning waking levels were equal to those of sleep. Waking adrenaline excretion correlated r=−0.59 with total sleep time. It was concluded that sleep exerts a strong inhibitory effect on both catecholamines and that, for adrenaline, this masking effect combines with circadian effects.

The suckling behavior of a captive beluga ( Delphinapterus leucas) calf

Observations of suckling activities of a beluga cow and calf were carried out during five 24-h watches from 3 to 38 days of age, and six 12-h watches from 52 to 109 days of age. The calf died at 111 days. No clear circadian pattern of suckling was seen in the first month. At 3 and 52 days of age, the calf intensively suckled another sub-adult female in the pool. Suckling patterns were irregular during the first month and then stabilised. The number of separate suckling attempts fluctuated considerably between ages but the number of suckling bouts were relatively constant. Tail flexing and rubbing of the mammaries on the bottom of the pool indicated that milk can be expelled from the beluga mammary by pressure external to the gland and in the absence of suckling.

Circadian rhythm in plasma concentrations of gamma-hydroxybutyric acid in alcoholics.

Gamma-hydroxybutyric acid (GHB) was orally administered to six alcoholics at 09.00 and 23.00 h. The plasma concentrations of GHB show a clear circadian pattern, the area under the curve in the daytime experiments being 61% of that in the night experiments. The significance of alcohol dehydrogenase, the catabolic enzyme of GHB, for the difference is discussed. It is concluded that, although the activity of alcohol dehydrogenase in alcoholics is quantitatively disturbed, it remains subject to physiologic circadian activation.