睡眠的记忆巩固功能研究进展

睡眠和学习记忆同属于大脑最重要的基本功能．大量的动物实验和人体研究都证明睡眠在记忆巩固中发挥重要作用．综合此领域近年来的研究成果,着重阐述睡眠期间海马和皮层的记忆巩固过程,并简要介绍所涉及的初步的细胞和分子机制．     

Phagocyte migration and cellular stress induced in liver, lung, and intestine during sleep loss and sleep recovery

Sleep is understood to possess recuperative properties and, conversely, sleep loss is associated with disease and shortened life span. Despite these critical attributes, the mechanisms and functions by which sleep and sleep loss impact health still are speculative. One of the most consistent, if largely overlooked, signs of sleep loss in both humans and laboratory rats is a progressive increase in circulating phagocytic cells, mainly neutrophils. The destination, if any, of the increased circulating populations has been unknown and, therefore, its medical significance has been uncertain. The purpose of the present experiment was to determine the content and location of neutrophils in liver and lung tissue of sleep-deprived rats. These are two principal sites affected by neutrophil migration during systemic inflammatory illness. The content of neutrophils in the intestine also was determined. Sleep deprivation in rats was produced for 5 and 10 days by the Bergmann-Rechtschaffen disk method, which has been validated for its high selectivity under freely moving conditions and which was tolerated and accompanied by a deep negative energy balance. Comparison groups included basal conditions and 48 h of sleep recovery after 10 days of sleep loss. Myeloperoxidase (MPO), an enzyme constituent of neutrophils, was extracted from liver, lung, and intestinal tissues, and its activity was determined by spectrophotometry. Leukocytes were located in vasculature and interstitial spaces in the liver and the lung by immunohistochemistry. Heme oxygenase-1, also known as heat shock protein-32 and a marker of cellular stress, and corticosterone also were measured. The results indicate neutrophil migration into extravascular liver and lung tissue concurrent with cell stress and consistent with tissue injury or infection induced by sleep loss. Plasma corticosterone was unchanged. Recovery sleep was marked by increased lung heme oxygenase-1, increased intestinal MPO activity, and abnormally low corticosterone, suggesting ongoing reactive processes as a result of prior sleep deprivation.     

非人灵长类动物模型睡眠研究在神经精神疾病的早期诊断和药效评价中的作用

清醒-睡眠的周期性调节需要众多单胺类神经递质(5-HT、NE、DA等)、乙酰胆碱等兴奋性神经递质以及GABA等抑制性神经递质的参与。这些递质系统的异常不仅会导致睡眠周期紊乱,还与一系列的精神性和神经退行性疾病相关。睡眠异常被认为是抑郁症、帕金森氏病等神经系统疾病发生的早期预警信号。相比起低等哺乳动物,非人灵长类动物的睡眠与人类的睡眠具有更好的可比性。近来,利用非人灵长类动物来建立神经精神疾病模型的研究已取得明显进展。在建模的同时监测动物的睡眠状况,有助于我们进一步了解睡眠在这些疾病早期诊断和发展过程中的作用,为疾病的早期诊断、治疗和药效评价提供更好的客观依据。     

Correlation of sleep disturbances, anxiety and depression in Croatian war veterans with posttraumatic stress disorder

The aim of the study was to examine the relationships between global sleep quality and its specific components and Posttraumatic Stress Disorder (PTSD) symptom severity questionnaire. We also researched whether sleep quality and sleep disturbances differed among groups of PTSD based on symptom severity categories. This study was conducted on the sample of 120 Croatian war veterans with PTSD. The following self-report instruments were used: Pittsburgh Sleep Quality Index, the Pittsburgh Sleep Quality Index Addendum for PTSD, the Mississippi Scale for Combat-Related PTSD, the Spielberger State and Trait Anxiety Inventory and the Beck Depression Inventory. There were statistically significant differences between the three PTSD severity groups on general nervousness (PSQI-A variable), where patients with extremely severe PTSD have more symptoms of general nervousness than groups with severe or moderate PTSD. Differences were found between PTSD severity groups in episodes of terror and acting-out dreams, where patients with extremely severe PTSD have more symptoms of episodes of terror and acting-out dreams than groups with severe or moderate PTSD. Sleep quality was significantly correlated with state anxiety, trait anxiety, and depression, indicating that with decrease of anxiety and depression, sleep quality improves. Sleep latency was positively correlated with both state and trait anxiety. There wasn't any significant correlation between sleep latency and depression. Study suggests that sleep disturbances are equally severe across groups of veterans based on PTSD severity and that the severity of sleep disturbances is significantly related to severity of anxiety and depression symptoms.     

Sleep as a fundamental property of neuronal assemblies

Sleep is vital to cognitive performance, productivity, health and well-being. Earlier theories of sleep presumed that it occurred at the level of the whole organism and that it was governed by central control mechanisms. However, evidence now indicates that sleep might be regulated at a more local level in the brain: it seems to be a fundamental property of neuronal networks and is dependent on prior activity in each network. Such local-network sleep might be initiated by metabolically driven changes in the production of sleep-regulatory substances. We discuss a mathematical model which illustrates that the sleep-like states of individual cortical columns can be synchronized through humoral and electrical connections, and that whole-organism sleep occurs as an emergent property of local-network interactions.     

Searching for sleep mutants of Drosophila melanogaster

The functions of sleep are still unknown, but are probably related to cellular and molecular aspects of neural function. To better understand the benefits that sleep may bring at the cellular level, recent studies have employed Drosophila melanogaster as a model system and shown that fruit flies share the fundamental features of mammalian sleep. As in mammals, sleep in Drosophila is characterized by increased arousal threshold and by changes in brain electrical activity. Fly sleep is homeostatically regulated independent of the circadian clock, is modulated by stimulants and hypnotics, and is affected by age. Also, fly sleep is associated with changes in brain gene expression similar to those observed in mammals. While Drosophila neurobiology is sufficiently complex to permit meaningful generalizations to mammals and humans, Drosophila genetics is simple enough to allow a rapid mutagenesis screening. An ongoing mutagenesis study has screened approximately 5000 mutant Drosophila lines and found that sleep amount, sleep pattern, and the homeostatic regulation of sleep are highly conserved phenotypes in flies. So far, this study has identified 10 short sleeper lines and 4 lines that show no sleep rebound after sleep deprivation. Ultimately, the characterization of these lines should help identifying crucial cellular pathways involved in the regulatory mechanisms of sleep and its functional consequences.     

Individual differences in the sleep/wake cycle of Arctic flexitime workers

Daytime workers tend to have shorter sleep duration and earlier sleep onset during work days than on days off. Large individual differences in sleep onset and sleep duration may be observed on work days, but work usually synchronizes sleep offset to a similar time. The present study describes individual differences in sleep behaviour of 48 daytime workers (25 men, aged 20–58 years) from an iron ore mine in Northern Sweden. The aim of the study was to determine whether differences in sleep patterns during work days were associated with the outcomes of sleepiness and sleep complaints. Cluster analysis was used to group workers into two categories of sleep onset and sleep duration. The “Late Sleep Onset” cluster comprised workers who slept 1.30 h later than the “Early Sleep Onset” cluster (p < 0.0001 for all weekdays). The “Long Sleep Duration” cluster slept 1.10 h longer than the “Short Sleep Duration” cluster (p < 0.0002 for work nights). The “Late Sleep Onset” cluster reported less refreshing sleep (p < 0.01) and had lower sufficient sleep scores (p < 0.01) than the “Early Sleep Onset” cluster. The “Short Sleep Duration” cluster also reported lower scores for sufficient sleep (p < 0.04) than the “Long Sleep Duration” cluster. For combined characteristics (phase and duration), workers with a late phase and short sleep duration reported greater sleep debt and sleepiness than workers with an early phase and short sleep duration (p < 0.02). Work schedule and commuting time modulate both sleep phase and sleep duration independently. Workers, classified as having an intermediate sleep phase preference, can organize their sleep time in order to minimize sleep debt and sleepiness symptoms. Individual differences in sleep phase and duration should be considered when promoting well-being at work even among groups with similar sleep needs. In order to minimize sleep debt and sleepiness symptoms, successful sleep behaviour could be promoted involving extend use of flexitime arrangement (i.e. later starting times) and reduce use of alarm clocks.     

Functional conservation of MBD proteins: MeCP2 and Drosophila MBD proteins alter sleep

Proteins containing a methyl‐CpG‐binding domain (MBD) bind 5mC and convert the methylation pattern information into appropriate functional cellular states. The correct readout of epigenetic marks is of particular importance in the nervous system where abnormal expression or compromised MBD protein function, can lead to disease and developmental disorders. Recent evidence indicates that the genome of Drosophila melanogaster is methylated and two MBD proteins, dMBD2/3 and dMBD‐R2, are present. Are Drosophila MBD proteins required for neuronal function, and as MBD‐containing proteins have diverged and evolved, does the MBD domain retain the molecular properties required for conserved cellular function across species? To address these questions, we expressed the human MBD‐containing protein, hMeCP2, in distinct amine neurons and quantified functional changes in sleep circuitry output using a high throughput assay in Drosophila. hMeCP2 expression resulted in phase‐specific sleep loss and sleep fragmentation with the hMeCP2‐mediated sleep deficits requiring an intact MBD domain. Reducing endogenous dMBD2/3 and dMBD‐R2 levels also generated sleep fragmentation, with an increase in sleep occurring upon dMBD‐R2 reduction. To examine if hMeCP2 and dMBD‐R2 are targeting common neuronal functions, we reduced dMBD‐R2 levels in combination with hMeCP2 expression and observed a complete rescue of sleep deficits. Furthermore, chromosomal binding experiments indicate MBD‐R2 and MeCP2 associate on shared genomic loci. Our results provide the first demonstration that Drosophila MBD‐containing family members are required for neuronal function and suggest that the MBD domain retains considerable functional conservation at the whole organism level across species.     

Relationship between insomnia and depression in a community sample depends on habitual sleep duration

Sleep and Biological Rhythms - Sleep disturbances, such as short sleep duration and insomnia, are core features of depression. However, it is unclear if sleep duration and insomnia have an...     

Effects of short- and long-term pulsed radiofrequency electromagnetic fields on night sleep and cognitive functions in healthy subjects

There has been wide public discussion on whether the electromagnetic fields of mobile telephones and their base stations affect human sleep or cognitive functioning. As there is evidence for learning and memory-consolidating effects of sleep and particularly of REM sleep, disturbance of sleep by radiofrequency electromagnetic fields might also impair cognitive functions. Previously realized sleep studies yielded inconsistent results regarding short-term exposure. Moreover, data are lacking on the effect that short- and long-term exposure might have on sleep as well as on cognitive functions. Therefore, 10 healthy young male subjects were included and nocturnal sleep was recorded during eight consecutive nights. In the second, third, and last night, we investigated polysomnographic night sleep and cognitive functions. After the adaptation and baseline nights, the participants were exposed to a defined radiofrequency electromagnetic field during the following six nights. We analyzed polysomnographic night sleep according to Rechtschaffen and Kales [1968, Manual of Standardized Terminology, Techniques and Scoring System for Sleep of Human Subjects] as well as by power spectra and correlation dimension. Cognitive functions were investigated by an array of neuropsychological tests. Data analysis was done by comparing the baseline night with the first and last exposure night and the first two sleep cycles of the respective nights. We did not find significant effects, either on conventional sleep parameters or on power spectra and correlation dimension, nor were there any significant effects on cognitive functions. With our results, we are unable to reveal either short-term or cumulative long-term effects of radiofrequency electromagnetic fields on night sleep and cognitive functions in healthy young male subjects.     

Sleep and nesting behavior in primates: A review

Sleep is a universal behavior in vertebrate and invertebrate animals, suggesting it originated in the very first life forms. Given the vital function of sleep, sleeping patterns and sleep architecture follow dynamic and adaptive processes reflecting trade-offs to different selective pressures. Here, we review responses in sleep and sleep-related behavior to environmental constraints across primate species, focusing on the role of great ape nest building in hominid evolution. We summarize and synthesize major hypotheses explaining the proximate and ultimate functions of great ape nest building across all species and subspecies; we draw on 46 original studies published between 2000 and 2017. In addition, we integrate the most recent data brought together by researchers from a complementary range of disciplines in the frame of the symposium “Burning the midnight oil” held at the 26th Congress of the International Primatological Society, Chicago, August 2016, as well as some additional contributors, each of which is included as a “stand-alone” article in this “Primate Sleep” symposium set. In doing so, we present crucial factors to be considered in describing scenarios of human sleep evolution: (a) the implications of nest construction for sleep quality and cognition; (b) the tree-to-ground transition in early hominids; (c) the peculiarities of human sleep. We propose bridging disciplines such as neurobiology, endocrinology, medicine, and evolutionary ecology, so that future research may disentangle the major functions of sleep in human and nonhuman primates, namely its role in energy allocation, health, and cognition.     

Sleep after vaccination boosts immunological memory

Sleep regulates immune functions. We asked whether sleep can influence immunological memory formation. Twenty-seven healthy men were vaccinated against hepatitis A three times, at weeks 0, 8, and 16 with conditions of sleep versus wakefulness in the following night. Sleep was recorded polysomnographically, and hormone levels were assessed throughout the night. Vaccination-induced Th cell and Ab responses were repeatedly monitored for 1 y. Compared with the wake condition, sleep after vaccination doubled the frequency of Ag-specific Th cells and increased the fraction of Th1 cytokine-producing cells in this population. Moreover, sleep markedly increased Ag-specific IgG1. The effects were followed up for 1 y and were associated with high sleep slow-wave activity during the postvaccination night as well as with accompanying levels of immunoregulatory hormones (i.e., increased growth hormone and prolactin but decreased cortisol release). Our findings provide novel evidence that sleep promotes human Th1 immune responses, implicating a critical role for slow-wave sleep in this process. The proinflammatory milieu induced during this sleep stage apparently acts as adjuvant that facilitates the transfer of antigenic information from APCs to Ag-specific Th cells. Like the nervous system, the immune system takes advantage of the offline conditions during sleep to foster adaptive immune responses resulting in improved immunological memory.     

Entrainment of Drosophila circadian rhythms by temperature cycles

Sleep and Biological Rhythms - The fruit fly, Drosophila melanogaster, has been a good organism for elucidating the molecular and cellular bases of circadian behavioral rhythms. The fly shows a...     

Actigraphic sleep and developmental progress of one-year-old infants

The aims of this study were to pilot methods to monitor the sleep of infants, as well as explore the relationships between infant sleep and physical, cognitive and motor development. Fifty-two one-year-old infants and their parents participated in the study. Infant sleep was assessed by one week’s actigraphy, sleep diaries and by the Brief Infant Sleep Questionnaire. Parents also completed a background questionnaire and the Ages and Stages Questionnaire to measure stages of development across five domains. Infant’s weight and length were measured by the researcher at study onset and Body Mass Index (BMI) scores were calculated. Sleep efficiency, and having a higher proportion of total sleep at night, were significantly correlated with age as well as stages of cognitive and motor development. However, sleep measures were not correlated with infant BMI. These findings support increasing evidence that sleep matures quickly around the age of one year and is related to other stages of development. Further research is required to confirm whether links between sleep and development are simply a marker of maturation, or if sleep per se plays a specific role in infant cognitive and motor development. Sleep and physical growth at this age need further investigation with a more representative sample including short-sleeping and overweight infants.

     

Disturbances of sleep and wakefulness associated with the use of antihypertensive agents

Sleep disturbances are frequently associated with the use of antihypertensive drugs. They are observed mainly during the administration of drugs that affect central adrenergic mechanisms. Beta-adrenoceptor antagonists which readily penetrate into the brain (propranolol, pindolol) increase wakefulness and/or decrease REM sleep. Alpha 2-adrenoceptor agonists (clonidine, guanfacine) markedly reduce the duration of REM sleep. The catecholamine depleting agent reserpine increases REM sleep during single or repeated-dose administration, while the MAOI phenelzine shows opposite effects. The 5-HT2 antagonist ritanserin, which is chemically related to the antihypertensive agent ketanserin, increases slow wave sleep while REM sleep is decreased. Sleep disturbances have not been reported during the administration of calcium entry antagonists. However, they seem to modify the effects of hypnotics and CNS stimulants. There are no formal studies on the effects of angiotensin converting enzyme inhibitors and vasodilators on sleep in man.     

Risk factors for sleep disorders in patients undergoing peritoneal dialysis

Sleep and Biological Rhythms - Sleep disorders in patients with end-stage renal disease are common but have rarely been reported in previous studies. Therefore, we examined the prevalence of sleep...     

Ambulatory sleep recording in a healthcare network: a feasibility study

Sleep disorders have a high prevalence: around 20% of insomniacs, 10% hypersomnolent including 2 to 4% of sleep disordered breathing in the general adult population. The low availability of sleep centres implies the research of alternative recording techniques in the natural setting of the patient. The objective was to evaluate an ambulatory recorder and its integration in a managed healthcare network. Fifteen patients had a full set-up at home and ten patients were hooked-up in the hospital but recorded at home. Technical failures occurred in 2/15 with full polysomnographic recordings. Integration within an experimental sleep network is in progress. This managed care network will include training of general practitioners, teletransmissions between GP and sleep specialists for a graded use of available resources including ambulatory monitoring.