Prion protein: a role in sleep regulation?
(9/1273)
The prion protein (PrP) is a glycoprotein anchored to cell membranes and expressed in most cell types. Its structural features indicate possible relations to signal peptidases (Glockshuber et al. 1998). Since mutations in this protein lead to severe neurodegeneration and death in humans and animals, it is possible that the loss of its normal function contributes to the development of the pathology. Little is known about its normal function, but there are indications that it may play a role in circadian rhythm and sleep regulation in mice. We explored further whether PrP plays a role in sleep regulation by comparing sleep and the effects of 6 h sleep deprivation in PrP knockout mice and isogenic wild-type mice of the 129/Ola strain. The mice did not differ in the amount and distribution of the vigilance states or in the power spectra. The most remarkable difference was the larger and long-lasting increase of slow-wave activity (mean EEG power density 0.75-4.0 Hz) in non-rapid-eye-movement (NREM) sleep during recovery from sleep deprivation in the null mice. The results confirm our previous findings in mice with a mixed background. This observation applies also to slow-wave activity in NREM sleep episodes following spontaneous waking bouts of different duration. Sleep fragmentation in both genotypes was larger than in mice with the mixed background. A new aspect was revealed by the spectral analysis of the EEG, where the null mice had a lower peak frequency within the theta band in REM sleep and waking, and not in NREM sleep. Behavioural observations concomitant with the EEG indicated that the EEG difference in waking may be attributed to the smaller amount of exploratory behaviour in the null mice. The difference between the genotypes in theta peak frequency was not an overall effect on the EEG, since it was absent in NREM sleep. PrP therefore may be affecting the theta-generating mechanisms in the hippocampus during waking and REM sleep. It remains unresolved whether PrP plays a role in sleep consolidation, nevertheless the data suggest that it is involved in sleep regulation. A passive avoidance test showed a difference between the genotypes. It is not probable that this was due to memory differences, since the genotypes reacted similarly in a delayed T-maze alternation procedure. The behavioural differences need to be pursued further. (+info)
Differences in brain gene expression between sleep and waking as revealed by mRNA differential display and cDNA microarray technology.
(10/1273)
The consequences of sleep and sleep deprivation at the molecular level are largely unexplored. Knowledge of such molecular events is essential to understand the restorative processes occurring during sleep as well as the cellular mechanisms of sleep regulation. Here we review the available data about changes in neural gene expression across different behavioural states using candidate gene approaches such as in situ hybridization and immunocytochemistry. We then describe new techniques for systematic screening of gene expression in the brain, such as subtractive hybridization, mRNA differential display, and cDNA microarray technology, outlining advantages and disadvantages of these methods. Finally, we summarize our initial results of a systematic screening of gene expression in the rat brain across behavioural states using mRNA differential display and cDNA microarray technology. The expression pattern of approximately 7000 genes was analysed in the cerebral cortex of rats after 3 h of spontaneous sleep, 3 h of spontaneous waking, or 3 h of sleep deprivation. While the majority of transcripts were expressed at the same level among these three conditions, 14 mRNAs were modulated by sleep and waking. Six transcripts, four more expressed in waking and two more expressed in sleep, corresponded to novel genes. The eight known transcripts were all expressed at higher levels in waking than in sleep and included transcription factors and mitochondrial genes. A possible role for these known transcripts in mediating neural plasticity during waking is discussed. (+info)
Exercise-induced changes in plasma atrial natriuretic peptide and brain natriuretic peptide concentrations in healthy subjects with chronic sleep deprivation.
(11/1273)
Recent observations have shown that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) correlate with cardiac function or prognosis in heart failure patients. However, relatively little is known about changes in their plasma concentration during commonly occurring physiological states such as fatigue. Therefore, this study was designed to examine the physiological changes of plasma ANP and BNP concentrations using a chronic sleep-deprivation model. Bicycle ergometer cardiopulmonary exercise tests were performed in 10 healthy volunteers (mean age: 22.7 years). Blood samples for measuring ANP and BNP were drawn during the resting state and immediately after each exercise test. Cardiac output (CO) was measured during the exercise test by the impedance method. The study conditions were designed as follows: (A) a day following a period of normal sleep (control state) and (B) a day preceded by 1 month during which sleep lasted <60% of normal (chronic sleep-deprived state). Results were as follows. (1) Peak oxygen uptake and peak CO decreased during the sleep-deprived state compared with the control state. (2) There was no difference between peak heart rates measured during exercise under the 2 conditions. (3) Plasma ANP concentration during exercise increased significantly during the control state, whereas only a tendency toward increase was observed during the sleep-deprived state. (4) Plasma BNP concentration during exercise tended to increase in the control state compared with the resting state, whereas there was no difference in plasma BNP between after exercise and resting state in the sleep-deprived state. These results indicate that changes of ANP or BNP induced by exercise tended to be decreased by chronic sleep deprivation. (+info)
Vehicle accidents related to sleep: a review.
(12/1273)
Falling asleep while driving accounts for a considerable proportion of vehicle accidents under monotonous driving conditions. Many of these accidents are related to work--for example, drivers of lorries, goods vehicles, and company cars. Time of day (circadian) effects are profound, with sleepiness being particularly evident during night shift work, and driving home afterwards. Circadian factors are as important in determining driver sleepiness as is the duration of the drive, but only duration of the drive is built into legislation protecting professional drivers. Older drivers are also vulnerable to sleepiness in the mid-afternoon. Possible pathological causes of driver sleepiness are discussed, but there is little evidence that this factor contributes greatly to the accident statistics. Sleep does not occur spontaneously without warning. Drivers falling asleep are unlikely to recollect having done so, but will be aware of the precursory state of increasing sleepiness; probably reaching a state of fighting off sleep before an accident. Self awareness of sleepiness is a better method for alerting the driver than automatic sleepiness detectors in the vehicle. None of these have been proved to be reliable and most have shortcomings. Putative counter measures to sleepiness, adopted during continued driving (cold air, use of car radio) are only effective for a short time. The only safe counter measure to driver sleepiness, particularly when the driver reaches the stage of fighting sleep, is to stop driving, and--for example, take a 30 minute break encompassing a short (< 15 minute) nap or coffee (about 150 mg caffeine), which are very effective particularly if taken together. Exercise is of little use. CONCLUSIONS: More education of employers and employees is needed about planning journeys, the dangers of driving while sleepy, and driving at vulnerable times of the day. (+info)
Diurnal variations and sleep deprivation-induced changes in rat hypothalamic GHRH and somatostatin contents.
(13/1273)
Previous reports indicate that hypothalamic growth hormone-releasing hormone (GHRH) promotes sleep and is involved in sleep regulation. The aim of our experiments was to determine whether the GHRH and somatostatin contents of the rat hypothalamus have diurnal variations and whether they are altered by sleep deprivation (SD). Hypothalamic samples were collected at 10 time points during the 24-h light-dark cycle. SD started at light onset. Hypothalamic samples were obtained after 4 and 8 h of SD and after 1 and 2 h of recovery following 8 h of SD. The peptides were determined by means of radioimmunoassay. GHRH displayed significant diurnal variations with low levels in the morning (a transient rise occurred at 1 h after light onset), gradual increases in the afternoon (peak at the end of the light period and beginning of the dark period), and decreases at night. SD induced significant GHRH depletion, which persisted during recovery. The afternoon rise was delayed, and the nocturnal decline of somatostatin was more rapid than the changes in GHRH. Although the patterns of the diurnal variations in GHRH and somatostatin were similar, there was no significant correlation between them. SD did not alter somatostatin significantly. Comparisons of the present results with previously reported changes in hypothalamic GHRH mRNA suggest that periods of deep nonrapid eye movement sleep (first portion of the light period and recovery sleep after SD) are associated with intense hypothalamic GHRH release. (+info)
The acceptability of sleep-deprived electroencephalograms.
(14/1273)
The aim of this study was to ascertain the acceptability of sleep-deprived EEGs to parents and their young child. Fifty unselected children having a sleep-deprived EEG were recruited. Data were collected from a sleep diary, a parent questionnaire and the request form of the EEG. Data collected covered developmental, learning and behavioural problems and the acceptability of the sleep-deprived EEG. There were 29 males (58%) in the study group. The average age was 8.6 years (range 2-17 years). Fifty percent of parents found it difficult to keep their child awake at night and 30% of parents found it difficult to wake their child in the morning. Fifty-four percent of parents reported their child had difficult behaviour on the day of the EEG. None had seizures provoked by sleep deprivation. (+info)
Sleep patterns and sleep-related complaints of Brazilian interstate bus drivers.
(15/1273)
Sleep-related complaints have become a highlight for physicians as well as public health administrators. Studies of sleep patterns and sleep-related complaints of shift workers have been useful in minimizing reduction in the quality of life due to the warping of the sleep-wake cycle. The objective of the present study was to assess patterns of sleep, sleep-related complaints as well as physical activity and scoring rates for depression and anxiety in interstate bus drivers. Data were obtained with a sleep questionnaire, with the Beck inventory for depression, and the State-Trait Anxiety Inventory (STAI). A total of 400 interstate bus drivers from the northern, southern, central-western and south-eastern regions of Brazil were interviewed. Sixty percent of the subjects interviewed presented at least one sleep-related complaint, 16% admitted to have dozed at the wheel while on duty, and 41% stated that they exercised on a regular basis. Other sleep disturbance complaints reported were: sleep latency 29'17"; physical fatigue, 59.8%; mental fatigue, 45.4%; sleepiness, 25.8%; irritability, 20.6%; insomnia, 37.5%, respiratory disturbances, 19. 25% and snoring, 20.75%. Scores for anxiety and depression were not in the pathological range. The present data reinforce the view that bus drivers are generally discontent with shift work and its effects on sleep. Consequently, it is very important to establish an appropriate work schedule for drivers, besides implementing photo-therapy and physical activities in order to minimize sleepiness when driving. (+info)
Does sleep fragmentation impact recuperation? A review and reanalysis.
(16/1273)
Studies have shown that next-day performance and alertness are impaired by sleep fragmentation procedures even when total sleep time (TST) is unaffected. Based on these studies it has been hypothesized that both the duration and continuity of sleep determine its recuperative value. This review of the literature suggests that when sleep fragmentation procedures increase the relative amount of stage 1 sleep, next-day performance and alertness are impaired. Other studies suggest that stage 1 sleep has little or no recuperative value. Total sleep time, however, is typically defined as the sum of time spent in sleep stages 1, 2, 3, 4, and REM. In the present paper it is shown that when stage 1 sleep is excluded from TST, a stronger relationship between TST and subsequent alertness and performance emerges--and the need to invoke 'sleep continuity' as a variable that contributes independently to recuperative sleep processes is obviated. In the same way that partial or total sleep deprivation impairs alertness and performance, it is proposed that sleep disruption also impairs alertness and performance by reducing true recuperative sleep time. (+info)