睡眠剥夺对大鼠免疫功能的影响

已有实验证明 ,睡眠剥夺或缺失可降低机体的防御能力。Ｂｒｏｗｎ[1 ] 曾发现睡眠剥夺能使小鼠对流感病毒的抵抗力减弱 ,ＩＬ 1或胞壁肽可对抗这一改变。相继的研究显示白细胞介素与肿瘤坏死因子等细胞因子可不同程度地促进睡眠[2 ] 。睡眠是否与免疫有关 ,本文拟通过对睡眠剥夺大鼠Ｔ细胞和Ｂ细胞增殖反应的变化 ,来探讨睡眠对免疫功能的影响。1　材料与方法1 1　主要仪器及药品 :刀豆蛋白Ａ(ＣｏｎＡ) ,北京中山生物公司 ;脂多糖 (ＬＰＳ) ,Ｓｉｇｍａ产品 ;四甲基偶氮唑盐 (ＭＴＴ) ,瑞士ＦＬＵＫＡ产品 ;十二烷基硫酸钠 (ＳＤＳ) ,日本…     

The effect of sleep deprivation on sleep in rats with suprachiasmatic lesions

The adenosine agonist 2-chloroadenosine inhibited the K+-induced release of endogenously synthesized [3H]glutamate but not [3H]GABA from slices of rat dentate gyrus. In contrast, the K+-stimulated release of [3H]glutamate was augmented by the adenosine antagonist theophylline and was further enhanced by the cyclic AMP analogue 8-bromo-cyclic AMP in the presence of theophylline.     

睡眠剥夺对大鼠海马miRNAs的影响

目的:探讨睡眠剥夺(sleep deprivation,SD)对成年大鼠海马miR132,miR138,miR127,miR128及let-7b的影响。方法:成年雄性Sprague-Dawley30只随机分为对照组(con),睡眠剥夺8 h组(sd8h),睡眠剥夺1 d组(sd1),睡眠剥夺3 d组(sd3),睡眠剥夺6 d组(sd6);采用改良多平台睡眠剥夺法(MMPM)建立大鼠SD模型,SYBRA greenⅠ荧光定量RT-PCR检测大鼠海马miRNAs的变化。结果:RT-PCR结果显示:(1)海马sd8 h组和sd1组miR132水平均低于control组(P0.05),但sd3组高于control组(P0.05);(2)海马sd8 h、sd3组miR138水平均低于control组(P0.01)但sd1组高于control组(P0.01);(3)海马sd8 h、sd1、sd3组miR127水平均低于control组(P0.05),但sd6组高于control组(P0.05);(4)海马sd1组miRl28水平低于control组(P0.05),sd8h组高于control组(P0.05);(5)海马sd8h、sdl、sd3组let-7b水平均高于control组(P0.05)。结论:睡眠剥夺可能与海马的miR132,miR138,miR127,miR128及let-7b的水平有关。     

Effects of sleep deprivation on wound healing

Sleep deprivation is widely regarded as a stressor and has been shown to have significant effects on host defences. Severely sleep-deprived rats develop lesions on their paws and tails, suggesting possible deficits in the healing process. The purpose of this study was to assess the impact of rapid eye-movement (REM) sleep deprivation (RSD) on wound healing in a rat model. Male dark-hooded Long-Evans rats, 2-4 months old, were subjected to dorsal application of two sterile punch biopsies, each 3.5 mm in size. Biopsies were performed either immediately before or immediately after 5 days of sleep deprivation. Wound healing in REM sleep-deprived animals was compared with home cage control and yoked control animals. RSD did not produce differences in the rate of healing, regardless of the timing of the biopsy punch. RSD does not appear to have significant effects on wound healing and thus appears to act differently from other types of stressors on wound healing.     

Effects of a 25-h sleep deprivation on daytime sleep in the middle-aged

Our understanding of the mechanisms by which sleep deteriorates with age almost exclusively stems from comparisons of young and elderly subjects. The present study investigated the different effects of a 25-h sleep deprivation on the recovery sleep initiated in the morning (when circadian sleep propensity decreases) of young (20-39 y) and middle-aged subjects (40-60 y). Middle-aged subjects showed a steeper increase in the duration of wakefulness during daytime recovery sleep than the young subjects. Slow-wave sleep (SWS) and EEG slow-wave activity (SWA: spectral power between 0.5-4.5 Hz) were potentiated in both groups following sleep deprivation. However, the rebound of SWS and SWA was significantly less pronounced in the middle-aged than in the young. This reduction in homeostatic recuperative drive in middle-aged subjects might account for the decrease in their ability to maintain sleep when they have to recuperate at an abnormal circadian phase. These results helps to understand the increase in complaints related to shift work and jet lag in the middle years of life.     

Effects of repeated deprivation of drinking water on the structure of renal medulla of rats.

Rats were exposed to repeated episodes of hydropenia for periods of 5 and 16 weeks, and structural alterations of renal medulla were investigated by light and electron microscopy. The hydropenia induced, within the inner medulla, focally severe structural changes in the tubular and endothelia and loss of interstitial cells. The findings present evidence that repeated episodes of hydropenia are capable of inducing cellular alterations of the renal medulla, particularly in the interstitial cells.     

Effects of paradoxical sleep deprivation in the rabbit

The effects of nonpharmacologically-induced deprivation of paradoxical sleep for a 24 hour period were studied in rabbits. Response characteristics commonly associated with the deprivation procedure in other species were observed, as well as features apparently peculiar to the rabbit. Like other mammals, rabbits: (1) show increased attempts to experience PS during the deprivation procedure relative to the baseline occurrence of PS; (2) become increasingly difficult to arouse from PS as the deprivation period progresses; (3) show increased amounts of PS (rebound) in post-deprivation recordings relative to baseline; and (4) compensate for only one-third of the PS deficit incurred during deprivation. Rabbits' response to PS deprivation differs from other mammals in the following ways: (1) the deprivation procedure is truly selective, significantly affecting only amounts of PS and not total sleep time or other sleep stages; (2) the rebound response is restricted to the light phase of the light-dark cycle on the first recovery day; and (3) as indexed by eye movement density, phasic activity during PS is not enhanced during the recovery period. Given that the crucial factor in the PS deprivation-compensation phenomenon is thought to be the deprivation and subsequent enhanced occurrence of phasic events, and considering that events within the oculomotor system have been emphasized in this regard, the results of this investigation suggest the existence of species differences regarding the nature and form of the compensatory response to PS deprivation.     

Effects of sleep deprivation on sleepiness and increased REM sleep in rats selectively bred for cholinergic hyperactivity.

In this study we employed a modification of the multiple sleep latency test (MSLT) to determine whether rats of a strain with increased cholinergic activity were sleepier compared to randomly bred control rats. Seven rats each from the Flinders sensitive line (FSL, hypercholinergic) and Flinders resistant line (FRL, age-matched controls) were kept awake for 20 min and then allowed to sleep ad libitum for 20 min. The regimen of 20 min of wakefulness followed by 20 min of sleep was repeated 12 times during the day. There were no differences in latency to sleep or to rapid eye movement (REM) sleep or in percent total sleep time, drowsy, or slow-wave sleep between FSL rats and FRL rats. However, FSL rats showed a significant increase in REM sleep compared to FRL rats. This selective increase in REM sleep may be coupled to an increase in brain muscarinic receptors in the FSL rats.     

Effects of anesthesia on the response to sleep deprivation

Study Objective:

Slow wave activity (SWA) during NREM sleep is the best characterized marker of sleep homeostasis, and the occurrence of sleep slow waves is necessary to reduce sleep need. Recent evidence suggests that sleep slow waves may mediate several beneficial effects of sleep on performance, from the prevention of cognitive impairments to memory consolidation. However, slow waves are also triggered by low doses of many anesthetics, but very few reports have examined whether anesthesia-mediated slow waves affect the homeostatic regulation of sleep. Moreover, no study has examined how sleep is affected by higher doses of anesthetics, which lead to a predominantly “isoelectric” EEG tracing without slow waves.

Design:

We studied in rats whether 1 hour of a dose of isoflurane or desflurane able to induce almost continuous slow waves (ISO-sw, DES-sw), and of a dose of desflurane resulting in a predominantly isoelectric EEG (DES-iso) reduces the sleep pressure caused by 4 h of sleep deprivation. Anesthesia was compared to a mock condition in which rats were only anesthetized for 2-3 min.

Setting:

Basic sleep research laboratory.

Patients or Participants:

Male WKY rats (n = 31).

Interventions:

Total sleep deprivation by exposure to novel objects starting at light onset, followed by one hour of anesthesia or mock anesthesia.

Measurements and Results:

One hour of anesthesia (sw or iso) did not affect either sleep duration or the overall sleep pattern. Anesthesia with ISO-sw or DES-sw, both associated with the occurrence of almost continuous slow waves, reduced the SWA rebound expected following 4 h of sleep deprivation. One hour of anesthesia with DES-iso, associated with isoelectric EEG and few slow waves, also reduced the SWA rebound after sleep deprivation, and did so to an extent similar to that observed after DES-sw. However, in contrast to DES-sw, SWA after DES-iso remained chronically lower than in baseline, resulting in reduced slow wave energy (SWE, SWA × time) for at least 2 days.

Conclusion:

The blunted SWA rebound after ISO-sw and DES-sw suggests that anesthesia slow waves may substitute for sleep slow waves. The reduced SWA rebound after DES-iso may reflect a pathological condition that results in a chronic decrease in SWA, or may suggest that anesthesia slow waves are not an absolute requirement to discharge sleep pressure.

Citation:

Nelson AB; Faraguna U; Tononi G; Cirelli C. Effects of anesthesia on the response to sleep deprivation. SLEEP 2010;33(12):1659-1667.     

Effects of age on recovery of body weight following REM sleep deprivation of rats

Chronically enforced rapid eye (paradoxical) movement sleep deprivation (REM-SD) of rats leads to a host of pathologies, of which hyperphagia and loss of body weight are among the most readily observed. In recent years, the etiology of many REM-SD-associated pathologies have been elucidated, but one unexplored area is whether age affects outcomes. In this study, male Sprague-Dawley rats at 2, 6, and 12 months of age were REM sleep-deprived with the platform (flowerpot) method for 10-12 days. Two-month-old rats resided on 7-cm platforms, while 10-cm platforms were used for 6- and 12-month-old rats; rats on 15-cm platforms served as tank controls (TCs). Daily changes in food consumption (g/kg(0.67)) and body weight (g) during baseline, REM-SD or TCs, and post-experiment recovery in home cages were determined. Compared to TCs, REM-SD resulted in higher food intake and decreases in body weight. When returned to home cages, food intake rapidly declined to baseline levels. Of primary interest was that rates of body weight gain during recovery differed between the age groups. Two-month-old rats rapidly restored body weight to pre-REM-SD mass within 5 days; 6-month-old rats were extrapolated by linear regression to have taken about 10 days, and for 12-month-old rats, the estimate was about 35 days. The observation that restoration of body weight following its loss during REM-SD may be age-dependent is in general agreement with the literature on aging effects on how mammals respond to stress.     

Effects of sleep deprivation on spontaneous arousals in humans

STUDY OBJECTIVES: The hierarchical definition of arousals from sleep includes a range of physiologic responses including microarousals, delta and K-complex bursts, and variations in autonomic system. Whether patterns in slow-wave electroencephalographic activity and autonomic activation are primary forms of arousal response can be addressed by studying effects of total sleep deprivation. We therefore examined changes in arousal density during recovery sleep in healthy subjects. DESIGN: Participants spent 6 consecutive 24-hour periods in the laboratory. Nights 1 and 2 were baseline nights followed by 64-hour total sleep deprivation, then 2 consecutive recovery nights. SETTING: Sleep-deprivation protocol was conducted under laboratory conditions with continuous behavioral and electrophysiologic monitoring. PARTICIPANTS: Twelve drug-free men aged 27.4 +/- 7.9 years were studied. None reported sleepiness or altered sleep-wake cycle, and none had neurologic, psychiatric or sleep disorders. INTERVENTION: N/A. MEASUREMENTS AND RESULTS: Arousals were classified into 4 levels: microarousals, phases of transitory activation, and delta and K-complex bursts. Sleep deprivation induced changes in the density of considered arousals except phases of transitory activation, with a distinct pattern among the different types. The greatest change was found for microarousals, which showed a significant decrease in the first recovery night (P = .01), with return to baseline thereafter. A fall in K-complex and delta-burst density was noted in the first recovery night, not, however, reaching statistical significance. The phases of transitory activation rate were virtually unaffected throughout the experimental nights. CONCLUSIONS: We conclude that homeostatic sleep processes exert an inhibitory effect on arousal response from sleep with a significant effect only on the microarousal density. Decreased delta and K-complex burst rates, though not significant, support the hypothesis that they may be activating processes, probably modulated by factors independent from those implicated in cortical arousal.     

Effects of sleep deprivation on sleepiness, sleep intensity, and subsequent sleep in the rat

The effects of 24 hr of sleep deprivation on cortical EEG and ventral hippocampus EEG recordings, ventral hippocampus spike rates, sleep stages percentages, and bout length measures were studied in rats. Two groups, differing only in the rate and distance they were forced to walk during deprivation by the water wheel method, were recorded continuously (23 hr per day) for one baseline, one deprivation, and two recovery days. During deprivation, microsleeps, increased hippocampal spike rates, and increased amplitude of the EEG recordings all suggested the intrusion of sleep processes. Nonetheless, there was no evidence to support the idea that these animals were not substantially deprived of sleep. No important differences were found in the recovery data of the two groups, even though one group walked three times as far as the other during deprivation. This supports the idea that, in conjunction with large amounts of sleep deprivation, changes in exercise and energy depletion may have little effect on sleep measures. During recovery, increased hippocampal spike rates and bout lengths, as well as increases in EEG amplitude, were interpreted in terms of increased sleep "intensity." High amplitude NREM sleep rebounded first, followed by rebounds in both paradoxical sleep and low amplitude NREM sleep. This pattern was compared to patterns previously reported for humans, cats, and rats. Finally, the tendency for some measures to fall below their baseline levels after an initial rebound was discussed in terms of "sleep inhibition" and servomechanism theory.     

Effects of pinealectomy on baseline sleep and response to sleep deprivation

STUDY OBJECTIVES: We have previously reported that older (24 mo.) Fischer rats manifest a diminished post-sleep deprivation increase in NREM and REM sleep. In order to examine whether this decline reflects an age-related change in pineal function, we are now reporting on baseline and recovery sleep parameters in pinealectomized 3-, 12-, and 24-month old rats following 24 hours of sleep deprivation using the disk-over-water method. DESIGN: Three independent age groups; within each group there were sequential measures of sleep under baseline conditions and during recovery from sleep deprivation. SETTING: The Sleep Research Laboratory at the University of Chicago PARTICIPANTS: 56 male Fisher (F344) rats INTERVENTIONS: 24 hours of total sleep deprivation using the disk-over-water method MEASUREMENTS: Sleep staging of EEG and EMG, and power spectral analysis of the EEG RESULTS: Pinealectomized (pinex) rats did not differ from sham-operated (sham) rats in total sleep, REM sleep, super-modal high-amplitude NREM sleep (HS2), a measure of NREM EEG delta power, or circadian rhythm amplitude. In the pinex rats, there was a modest (2.5%) age-independent increase in NREM sleep (p<0.02). The pinex rats of all ages failed to manifest the increase in NREM sleep during recovery seen in the sham-operated animals (p<0.04). CONCLUSIONS: We found no evidence that altered pineal function is responsible for age-related changes in baseline sleep in the rat. These data also suggest that, independent of age, normal pineal function may be relevant to the ability to generate increased NREM sleep in response to prior sleep deprivation.     

REM sleep deprivation impairs muscle regeneration in rats

Introduction: The aim was observe the influence of sleep deprivation (SD) and sleep recovery on muscle regeneration process in rats submitted to cryolesion.

Methods: Thirty-two Wistar rats were randomly allocated in four groups: control (CTL), SD for 96?h (SD96), control plus sleep recovery period (CTL?+?R) and SD96h plus 96?h of sleep recovery (SD96?+?R). The animals were submitted to muscle injury by cryolesioning, after to SD and sleep recovery.

Results: The major outcomes of this study were the reduction of muscular IGF-1 in both legs (injured and uninjured) and a delay in muscle regeneration process of animals submitted to SD compared to animals that slept, with increase connective tissue, inflammatory infiltrate and minor muscle fibers.

Conclusions: SD impairs muscle regeneration in rats, moreover reduces muscular IGF-1 and sleep recovery was able to restore it to basal levels, but it was not enough to normalize the muscle regeneration.     

REM sleep deprivation diminishes fear in rats.

To test the hypothesis that REM sleep deprivation decreases fear, the behavior of 44 rats was measured in an open-field test. Prior to this test, the animals were exposed to 4 days to one of four treatments, i.e., either a dry environment control, a wet environment control, a 2-day REM deprivation period, or a 4-day REM deprivation period. During the test both exploration and three parameters of emotionality were recorded. The results offered convincing evidence in support of the hypothesis.     

REM sleep deprivation impairs latent extinction in rats

Preextinction exposure to some aspects of the nonreward condition has been shown to facilitate extinction of bar pressing. Deprivation of REM sleep immediately following preextinction experience blocked this facilitation. REM sleep appears to be necessary for assimilation of the preextinction experience.     

Effects of sleep deprivation on serum testosterone concentrations in the rat

Sleep deprivation (SD) leads to decreases in circulating levels of testosterone with unknown mechanisms. We tested the hypothesis that decreased testosterone levels associated with SD may be caused by serotonin-mediated inhibition of its production. Male rats were subjected to SD for 24 or 48 h using the dish-over-water-method with a Rechtschaffen apparatus. Serum testosterone, corticosterone and serotonin (5-HT) concentrations were assessed thereafter, as were testicular StAR and 5-HT 2 receptor levels. SD, regardless of duration led to significant decreases in serum testosterone levels and testicular steroid acute regulatory protein (StAR) protein expression, while 5-HT levels were significantly elevated (all P<0.05). Corticosterone concentrations were significantly increased in 48 h SD rats (P<0.05). In primary Leydig cell cultures, 5-HT decreased chorionic gonadotropin-induced testosterone secretion and StAR expression, which appeared to be dependent on 5-HT 2 receptor activation but independent of cyclic AMP signaling. These findings suggest that decreased serum testosterone levels in SD rats may be the result of 5-HT-related inhibition of testosterone production and decreased testicular expression of StAR protein.     

REM sleep deprivation impairs bar-press acquisition in rats

Brief REM sleep deprivation immediately after training temporarily retarded bar-press acquisition, abolished observational learning of the bar-press habit, and prevented adaptation to a shift from a CRF to a DRL schedule. These results support the information-processing model of REM sleep function.     

Effects of sleep deprivation on daytime sleepiness in primary insomnia

STUDY OBJECTIVES: This study investigated changes in MSLT scores and recovery sleep following total sleep deprivation in subjects with insomnia as compared to normal sleepers. DESIGN: Matched-groups design. SETTING: A sleep disorders center in a large medical center. PARTICIPANTS: Ten individuals with psychophysiological insomnia and ten age- and sex-matched normal sleepers served as subjects. INTERVENTIONS: Subjects underwent total sleep deprivation after baseline polysomnography and MSLT. A post-deprivation MSLT was obtained, as well as polysomnography on the recovery night and an MSLT after the recovery night. MEASUREMENTS AND RESULTS: Both groups showed significant decreases in MSLT scores following total sleep deprivation, as compared to baseline. Both groups had significantly shorter scores on a nighttime MSLT compared to a daytime MSLT. The insomnia group also showed a significant increase in total sleep time on the recovery night compared to baseline. CONCLUSIONS: The MSLT is sensitive to changes in sleepiness associated with total sleep deprivation in individuals with primary insomnia.     

Age-dependent changes in recovery sleep after 48 hours of sleep deprivation in rats

To characterize possible changes in homeostatic regulation of sleep with aging, we have examined sleep stages during recovery sleep after 48 h of sleep deprivation in young (3 months), middle aged (12 months), and old (24 months) rats. It was found that young and middle aged, in contrast to old rats, had large (21-24%) increases in total sleep time during recovery sleep; the old rats experienced a quantitatively small (8%) but significant rise in total sleep. NREM sleep increased significantly during the recovery period in young and middle aged, but not older rats. High voltage NREM sleep (HS2) declined by 30% during recovery in the young animals, but remained unchanged compared to baseline in the middle aged and old animals. The young and middle aged rats had increases in REM sleep during recovery compared to their baseline by 96% and 93%, respectively, which was significantly greater than a 65% increase during recovery in the old rats. Increases in total sleep and REM sleep during recovery were largely confined to the first 6 h in young and middle aged rats, but maxima for the old rats occurred in the second 6 h.