Diurnal change in stature: effects of sleep deprivation in young men and middle-aged men

Sleep deprivation was associated with decreased stature and it blunted the normal 24-h rhythm in young and in middle-aged men. Loss in stature was regained during the first recovery night of sleep. The 24-h rhythm in height is not an endogenous circadian rhythm but depends upon the periods of recumbency over the sleep/wake cycle.     

Effects of vitamin B12 on plasma melatonin rhythm in humans: Increased light sensitivity phase-advances the circadian clock?

Vitamin B12 (methylcobalamine) was administered orally (3 mg/day) to 9 healthy subjects for 4 weeks. Nocturnal melatonin levels after exposure to bright light (ca. 2500 lx) were determined, as well as the levels of plasma melatonin over 24 h. The timing of sleep was also recorded. Vitamin B12 was given blind to the subjects and crossed over with placebo. We found that the 24-h melatlonin rhythm was significantly phase-advanced (1.1. h) in the vitamin B12 trial as compared with that in the placebo trial. In addition, the 24-h mean of plasma melatonin level was much lower in the vitamin B12 traial than with the placebo. Furthermore, the nocturnal melatonin levels during bright light exposure were significantly lower in the vitamin B12 trial than with the placebo. On the other hand, vitamin B12 did not affect the timing of sleep. These findings raise the possibility that vitamin B12 phase-advances the human circadian rhythm by increasing the light sensitivity of the circadian clock.     

Effects of vitamin B12 on plasma melatonin rhythm in humans: increased light sensitivity phase-advances the circadian clock?

Vitamin B12 (methylcobalamin) was administered orally (3 mg/day) to 9 healthy subjects for 4 weeks. Nocturnal melatonin levels after exposure to bright light (ca. 2500 lx) were determined, as well as the levels of plasma melatonin over 24 h. The timing of sleep was also recorded. Vitamin B12 was given blind to the subjects and crossed over with placebo. We found that the 24-h melatonin rhythm was significantly phase-advanced (1.1 h) in the vitamin B12 trial as compared with that in the placebo trial. In addition, the 24-h mean of plasma melatonin level was much lower in the vitamin B12 trial than with the placebo. Furthermore, the nocturnal melatonin levels during bright light exposure were significantly lower in the vitamin B12 trial than with the placebo. On the other hand, vitamin B12 did not affect the timing of sleep. These findings raise the possibility that vitamin B12 phase-advances the human circadian rhythm by increasing the light sensitivity of the circadian clock.     

Chronobiology of sleep in humans

Periodic circadian (24-h) cycles play an important role in daily hormonal and behavioural rhythms. Usually our sleep/wake cycle, temperature and melatonin rhythms are internally synchronized with a stable phase relationship. When there is a desynchrony between the sleep/wake cycle and circadian rhythm, sleep disorders such as advanced and delayed sleep phase syndrome can arise as well as transient chronobiologic disturbances, for example from jet lag and shift work. Appropriately timed bright light is effective in re-timing the circadian rhythm and sleep pattern to a more desired time, ameliorating these disturbances. Other less potent retiming effects may also be obtained from the judicious use of melatonin and exercise.     

Rhythms of enzymatic activity in maternal and umbilical cord blood

The 24-h activity patterns of variouns enzymes were determined in human serum, red blood cells and white blood cells of maternal and umbilical cord blood. Blood was drawn from the brachial vein of mothers and from the umbilical cord within ten minutes after delivery. Corresponding blood specimens were obtained from 83 spontaneous labors, occurring at different hours over a period of 60 days. For each variable (variable=activity of a specific enzyme in one of the blood components) the results were grouped according to delivery hour, forming a 24-h pattern which was analyzed to elucidate time dependency. Five out of six corresponding maternal and fetal variables were similar with regard to pattern and peak time. The activity rhythms of glyceraldehyde-3-phosphate dehydrogenase and glucose phosphate isomerase in red blood cells of mothers and fetuses possessed a significant bimodal pattern. The activity rhythms of the latter enzyme in white blood cells and sera exhibited a significant 24-h period. Hexosaminidase activity exhibited a distinct 24-h rhythm in maternal white blood cells, but no significant rhythm could be detected in the fetal white blood cells. The activity of hexosaminidase showed, identical 24-h patterns in maternal and cord serum when analyzed by best fit cosine, and no significant time-dependency when analyzed by ANOVA.     

Rhythms of enzymatic activity in maternal and umbilical cord blood.

The 24-h activity patterns of various enzymes were determined in human serum, red blood cells and white blood cells of maternal and umbilical cord blood. Blood was drawn from the brachial vein of mothers and from the umbilical cord within ten minutes after delivery. Corresponding blood specimens were obtained from 83 spontaneous labors, occurring at different hours over a period of 60 days. For each variable (variable = activity of a specific enzyme in one of the blood components) the results were grouped according to delivery hour, forming a 24-h pattern which was analyzed to elucidate time dependency. Five out of six corresponding maternal and fetal variables were similar with regard to pattern and peak time. The activity rhythms of glyceraldehyde-3-phosphate dehydrogenase and glucose phosphate isomerase in red blood cells of mothers and fetuses possessed a significant bimodal pattern. The activity rhythms of the latter enzyme in white blood cells and sera exhibited a significant 24-h period. Hexosaminidase activity exhibited a distinct 24-h rhythm in maternal white blood cells, but no significant rhythm could be detected in the fetal white blood cells. The activity of hexosaminidase showed, identical 24-h patterns in maternal and cord serum when analyzed by best fit cosine, and no significant time-dependency when analyzed by ANOVA.     

Long-term motor activity recording of dogs and the effect of sleep deprivation

Summary Motor activity of laboratory dogs was recorded for several weeks with an ambulatory monitoring device. The effect of 24 h sleep deprivation (SD) on motor activity during recovery was investigated. A clear rest-activity rhythm was established. The dogs exhibited a similar mean daily rest-activity pattern: 1) rest occurred mainly in the dark; 2) the amimals were most active after light onset; activity increased during the last two dark hours; 3) a rest period was found at noon and reduced activity during afternoon hours. There was a marked difference in total activity between individual dogs. Activity patterns varied as a function of the day of the week; this may have been a reflection of variations in the level of human activities in the laboratory. There was a significant reduction of motor activity during the 24-h period following SD. This was particularly evident in the first 6 h of the light period immediately following the deprivation.In addition, there was a significant increase in the number of episodes with activity 5 counts during recovery. The study confirms the possibility of measuring motor activity to assess compensatory mechanisms during recovery after SD. Sleep regulation, therefore, does not necessarily need to be exclusively examined by the invasive technique of EEG registration.     

Ein 24-Stunden-Rhythmus des Herz- und Milzglykogens der weissen Laboratoriumsratte

Summary A definite 24-h rhythm was demonstrated in the glycogen content of heart muscle and of spleen of white laboratory rats, which makes it essential to take account of this fact when interpreting experimental results on these organs.     

Experimental dissociation between hippocampal theta activity in wakefulness and hippocampal theta activity in paradoxal sleep in the rat]

The effects of electrolytic lesion of the septum on the theta activity of the dorsal hippocampus were studied in the chronically implanted Rat during wakefulness and paradoxical sleep. The experimental results show that depending on its localization, septal lesion can either: (1) eliminate the wakefulness theta rhythm without suppressing that of paradoxical sleep; (2) eliminate the paradoxical sleep theta rhythm without suppressing that of wakefulness. These results suggest that there are two kinds of theta activity having different anatomophysiological bases and a different functional significance: one associated with wakefulness and the other with paradoxical sleep.     

Effects of bilateral dorsolateral pontine tegmentum lesions on hippocampus theta rhythm during paradoxical sleep in the rat]

Electrolytic lesions of the dorsolateral pontine tegmentum aimed at the locus coeruleus (LC) were performed bilaterally in 13 chronically implanted Rats. Following lesions, transient alterations of characteristic components of theta rhythm appeared. No shortening of duration of paradoxical sleep (PS) was observed. These results do not support the hypothesis that neurons of LC are directly involved in the production of theta rhythm during PS; moreover they seem not to be necessary to the normal appearance of this state of sleep.     

Exogenous melatonin accelerates re-entrainment: Attenuation of the circadian rhythm of metabolic rate in the canary,Serinus canaria

Administration of melatonin in the drinking water (200 g/ml in 1% ethanol) decreased the time of re-entrainment of the circadian rhythm of the metabolic rate (measured as oxygen uptake) of domestic canaries (Serinus canaria) after 10-h delay phase shifts of the light-dark (LD) cycle by 1.3 days on average. Associated with faster re-entrainment, the amplitude of the metabolic rhythm was attenuated by 46% on, average on the first day after the shift as compared with about 25% in the controls. After re-entrainment, the amplitude of the metabolic rhythm during melatonin administration was about 23% lower than in the controls. The minimum resting metabolic rate increased by ca 5% on average during treatment with melatonin. The results are consistent with the hypothesis that constant high plasma levels of melatonin act on higher levels of the circadian oscillatory system rather than by directly affecting peripheral or central photoreceptors.     

Pineal function in the sheep: evidence for a possible mechanism mediating seasonal reproductive activity

Summary The 24-h profiles of plasma melatonin in the intact ewe in natural light indicate that a bimodal pattern of secretion is frequently present in oestrus, whereas a single dark-phase peak is characteristic of anoestrus. Based on these findings, a mechanism for the possible pineal-mediated control of seasonal breeding is proposed.This work was supported by the Medical Research Council and the Agricultural Research Council of Great Britain. Preliminary results from this study were reported in the proceedings of the 1st meeting of the European Pineal Study Group; J. Arendt, Prog. Brain Res.52, 249 (1979).We are grateful for the excellent technical assistance of A. Marston and J. Bradtke.     

Human slow wave sleep: A review and appraisal of recent findings,with implications for sleep functions,and psychiatric illness

Recent findings concerning human slow wave sleep (hSWS-stages 3+4; delta EEG activity) are critically reviewed. Areas covered include the significance of the first hSWS cycle; hSWS in extended sleep; relationship between hSWS, prior wakefulness and sleep loss; hSWS influence on sleep length; problems with hSWS deprivation; influence of the circadian rhythm; individual differences in hSWS, especially, age, gender and constitutional variables such as physical fitness and body composition. Transient increases in hSWS can be produced by increasing both the quality and quantity of prior wakefulness, with an underlying mechanism perhaps relating to the waking level of brain metabolism. Whilst there may also be thermoregulatory influences on hSWS, hypotheses that energy conservation and brain cooling are major roles for hSWS are debatable. hSWS seems to offer some form of cerebral recovery, with the prefrontal cortex being particularly implicated. The hSWS characteristics of certain forms of major psychiatric disorders may well endorse this prefrontal link.     

Human slow wave sleep: a review and appraisal of recent findings, with implications for sleep functions, and psychiatric illness.

Recent findings concerning human slow wave sleep (hSWS-stages 3 + 4; delta EEG activity) are critically reviewed. Areas covered include the significance of the first hSWS cycle; hSWS in extended sleep; relationship between hSWS, prior wakefulness and sleep loss; hSWS influence on sleep length; problems with hSWS deprivation; influence of the circadian rhythm; individual differences in hSWS, especially, age, gender and constitutional variables such as physical fitness and body composition. Transient increases in hSWS can be produced by increasing both the quality and quantity of prior wakefulness, with an underlying mechanism perhaps relating to the waking level of brain metabolism. Whilst there may also be thermoregulatory influences on hSWS, hypotheses that energy conservation and brain cooling are major roles for hSWS are debatable. hSWS seems to offer some form of cerebral recovery, with the prefrontal cortex being particularly implicated. The hSWS characteristics of certain forms of major psychiatric disorders may well endorse this prefrontal link.     

Development of post-hatching melatonin rhythm in zebra finches (Poephila guttata)

We examined levels of melatonin in the pineal, eyes and plasma over a 24 h period during development in the altricial zebra finch. Beginning as early as 2 days after hatching there was a distinct 24 h rhythm in melatonin in the pineal and plasma. Beginning at day seven after hatching there was also a 24 h rhythm present in the eyes. In the pineal and eyes the amplitude of the 24 h rhythm increased with age. In contrast, the amplitude of the plasma melatonin rhythm at 2 days was already within the range of adults and did not increase with age. These results confirm and expand earlier findings in the European starling and parallel those from precocial birds indicating that the circadian system is already competent at or shortly after hatching even in atricial birds.     

Sex differences in human circadian rhythms: Intrinsic periods and sleep fractions

Summary The period of freerunning circadian rhythms is significantly shorter and the fraction of sleep is significantly larger in human females than in males, as long as the rhythms run internally synchronized. The sex difference in the period could be a property either of the whole circadian system or of only one of the oscillators in a multi-oscillator system. The sex difference in the sleep fraction could be a fixed property of the sleep-wake rhythm or could depend on interactions in the multi-oscillator system. To investigate these questions, a sample of 33 long-term experiments, in which the rhythms ran internally synchronized in one section and internally desynchronized in another section, were analyzed. The periods of rhythms in rectal temperature were different in females and males during internal synchronization, but became identical during internal desynchronization. In contrast, sex differences in sleep-wake periods were more pronounced when the rhythms were desynchronized than when they were internally synchronized. This result provides evidence that the sex difference in periodicity is a property only of the sleep-wake rhythm; the intrinsic periods of temperature rhythms are identical in females and males, whereas those of sleep-wake rhythms are distinctly shorter in females than in males. In the state of internal synchronization, the joint period is a compromise between the intrinsic periods of the rhythms involved, and therefore it shows a small but significant sex difference. Moreover, the transition from internally synchronized to desynchronized rhythms is combined with a highly significant reduction in the sleep fraction, which is considerably greater in females than in males. These results suggest that the occurrence of internal desynchronization strongly affects the sleep-wake rhythm, and that the influence of rhythm disorders is considerably greater in females than in males.     

Circabidian rhythm: its appearance and disappearance in association with a bright light pulse

A shift from circadian to circabidian periods or vice versa was observed in the rhythm of sleep and wakefulness under temporal isolation. The shift occurred in two subjects, 3 times in association with a single bright light pulse applied, 4 times in all. The finding suggests that the bright light pulse has an additional effect to the phase shift on the human circadian system.     

Persistent 24-h variations of urinary 6-hydroxy melatonin sulphate and cortisol in Antarctica

Bright light (2000-3000 lux) of sufficient intensity to suppress human melatonin secretion, acts as a strong zeitgeber in the entrainment of circadian rhythms in man. In polar conditions, light of this intensity is not experienced for several weeks during the winter. The entrainment of human circadian rhythms, in particular that of melatonin, is clearly of interest in these circumstances. Urinary 6-hydroxy melatonin sulphate (aMT6s) is a good index of melatonin secretion in man. In a limited study of seven male volunteers living on an Antarctic base the overall 24-h rhythm of aMT6s excretion was maintained at four different times of year (spring, summer, autumn and winter) and no significant seasonal effects were noted. Cortisol excretion, appeared to be markedly affected by the season although other factors such as social and environmental stress cannot be discounted. These observations suggest that in the absence of a strong light-dark cycle melatonin production may be entrained by other factors.     

Ontogenetic analysis of the theta rhythm during paradoxical sleep in rats]

In the rat, an ontogenetic study of theta rhythm during paradoxical sleep shows a clear evolution between the 14th and the 30th postnatal day. During this period, its mean frequency increases from 5 to 7 cycles per second, and its spectrum shows significant changes. These parameters (mean frequency and spectral components) of the theta rhythm could be a useful index of brain maturation in the rat.