OBJECTIVES: To assess the regulatory effect of cannabidiol (CBD) on circadian rhythm sleep disorders following general anesthesia and explore its potential mechanism in a rat model of propofol-induced rhythm sleep disorder. METHODS: An electrode was embedded in the skull for cortical EEG recording in 24 male SD rats, which were randomized into control, propofol, CBD treatment, and diazepam treatment groups (n=6). Eight days later, a single dose of propofol (10 mg/kg) was injected via the tail vein with anesthesia maintenance for 3 h in the latter 3 groups, and daily treatment with saline, CBD or diazepam was administered via gavage; the control rats received only saline injection. A wireless system was used for collecting EEG, EMG, and body temperature data within 72 h after propofol injection. After data collection, blood samples and hypothalamic tissue samples were collected for determining serum levels of oxidative stress markers and hypothalamic expressions of the key clock proteins. RESULTS: Compared with the control rats, the rats with CBD treatment showed significantly increased sleep time at night (20:00-6:00), especially during the time period of 4:00-6:00 am. Compared with the rats in propofol group, which had prolonged SWS time and increased sleep episodes during 18:00-24:00 and sleep-wake transitions, the CBD-treated rats exhibited a significant reduction of SWS time and fewer SWS-to-active-awake transitions with increased SWS aspects and sleep-wake transitions at night (24:00-08:00). Diazepam treatment produced similar effect to CBD but with a weaker effect on sleep-wake transitions. Propofol caused significant changes in protein expressions and redox state, which were effectively reversed by CBD treatment. CONCLUSIONS CBD can improve sleep structure and circadian rhythm in rats with propofol-induced sleep disorder possibly by regulating hypothalamic expressions of the key circadian clock proteins, suggesting a new treatment option for perioperative sleep disorders.
Animals ; Rats, Sprague-Dawley ; Male ; Cannabidiol/therapeutic use* ; Rats ; Circadian Rhythm/drug effects* ; Propofol/adverse effects* ; Anesthesia, General/adverse effects* ; Sleep Wake Disorders/chemically induced* ; Hypothalamus/metabolism* ; Electroencephalography

Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.
Animals ; Zebrafish ; Melatonin/pharmacology* ; Lipid Metabolism/drug effects* ; Disease Models, Animal ; Rotenone/pharmacology* ; Sleep Wake Disorders/metabolism* ; Parkinson Disease/metabolism* ; Motor Activity/drug effects* ; Sleep/drug effects*

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.
Animals ; Mice ; Corticotropin-Releasing Hormone/metabolism* ; Nucleus Accumbens/metabolism* ; Receptors, Corticotropin-Releasing Hormone/metabolism* ; Sleep ; Sleep Wake Disorders ; Stress, Psychological/complications*

Sleep is an extremely important physiological state to maintain human life. Sleep disorders can not only cause anxiety and depression, but also induce multi-system diseases that seriously affect brain function and physical health. The neuroinflammation is a key pathological process after sleep disorders, which can induce a series of nervous system diseases. In recent years, the role of microglia activation in neuroinflammation has been paid more and more attention and become a research hotspot in this field. The imbalance of the central microenvironment after sleep disorders leads to changes in the activation and polarization of microglia, which triggers neuroinflammatory response. The activation and polarization of microglia in the sleep disorders are regulated by multiple signaling pathways and complex molecular mechanisms. This paper summarizes five signaling pathways of microglia activation in central inflammation induced by sleep disorders, including P2X7 receptor (P2X7R), p38MAPK, Toll-like receptor 4 (TLR4)/NF-κB, JAK/STAT, and α7 nicotinic acetylcholine receptor (α7-nAChR) pathways, in order to provide reference for further research and clinical treatment targets selection of sleep disorders.
Humans ; Neuroinflammatory Diseases ; Microglia/metabolism* ; Signal Transduction/physiology* ; NF-kappa B/metabolism* ; Inflammation/metabolism* ; Sleep Wake Disorders/metabolism*

BACKGROUNDStudies have reported the presence of sleep disorders in approximately 50-70% of diabetic patients, and these may contribute to poor glycemic control, diabetic neuropathy, and overnight hypoglycemia. The aim of this study was to determine the frequency of sleep disorders in diabetic patients, and to investigate possible relationships between scores of these sleep disorders and obstructive sleep apnea syndrome (OSAS) and diabetic parameters (fasting blood glucose, glycated hemoglobin A1c [HbA1c], and lipid levels).

METHODSWe used the Berlin questionnaire (BQ) for OSAS, the Epworth Sleepiness Scale (ESS), and the Pittsburgh Sleep Quality Index (PSQI) to determine the frequency of sleep disorders and their possible relationships with fasting blood glucose, HbA1c, and lipid levels.

RESULTSThe study included 585 type 2 diabetic patients admitted to family medicine clinics between October and December 2014. Sleep, sleep quality, and sleep scores were used as the dependent variables in the analysis. The ESS scores showed that 54.40% of patients experienced excessive daytime sleepiness, and according to the PSQI, 64.30% experienced poor-quality sleep. The BQ results indicated that 50.20% of patients were at high-risk of OSAS. HbA1c levels correlated significantly with the ESS and PSQI results (r = 0.23, P < 0.001 and r = 0.14, P = 0.001, respectively), and were significantly higher in those with high-risk of OSAS as defined by the BQ (P < 0.001). These results showed that HbA1c levels were related to sleep disorders.

CONCLUSIONSSleep disorders are common in diabetic patients and negatively affect the control of diabetes. Conversely, poor diabetes control is an important factor disturbing sleep quality. Addressing sleep disturbances in patients who have difficulty controlling their blood glucose has dual benefits: Preventing diabetic complications caused by sleep disturbance and improving diabetes control.

Diabetes Mellitus, Type 2 ; blood ; metabolism ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Male ; Middle Aged ; Sleep Apnea, Obstructive ; blood ; complications ; Sleep Wake Disorders ; blood ; complications

BACKGROUNDThe prevalence of sleep disorders has been shown to be high in patients with chronic dialysis patients and may contribute to impaired quality of life and higher mortality in this population. However, there are few data on the relationship of sleep disorders and their risk factors in chronic dialysis patients. The aim of this study was to evaluate the relationship of sleep disorders and their risk factors in chronic dialysis patients.

METHODSA total of 42 continuous ambulatory peritoneal dialysis (CAPD) patients were involved in this cross-sectional study. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Restless legs syndrome (RLS) was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group. And depression was assessed by Hamilton depression scale. General information and laboratory data were collected.

RESULTSThe prevalence of sleep disorders was 47.6% in the CAPD patients. According to the PSQI, the 42 CAPD patients were divided into sleep disturbance group and non-sleep disorders group. There were no significant differences in age, gender, dialysis duration, hemoglobin, serum creatinine, urea nitrogen, β2-microglobulin, parathyroid hormone, calcium, and phosphorus between CAPD patients with sleep disorders and those without sleep disorders. But the level of serum albumin (Alb) in CAPD patients with sleep disorders was significantly lower than that in CAPD patients without sleep disorders (31.3 ± 1.4 vs. 34.3 ± 3.7, t = 3.603, P = 0.001) . And the prevalence of RLS and depression was significantly higher than that in CAPD patients without sleep disorders (RLS: 11/22 vs. 1/20, χ(2) = 10.395, P = 0.001; depression: 7/22 vs. 1/20, χ(2) = 4.886, P = 0.027). In CAPD patients with RLS, the prevalence of sleep disorders was significantly higher than that in CAPD patients without RLS (11/22 vs. 11/30, χ(2) = 10.395, P = 0.001). And in CAPD patients with depression, the prevalence of sleep disorders was significantly higher than that in CAPD patients without depression (7/8 vs. 15/34, χ(2) = 4.886, P = 0.027). In CAPD patients, bivariate correlation analysis showed that sleep disorders was negatively correlated with serum Alb (r = -0.606, P = 0.000) and positively correlated with RLS (r = 0.497, P = 0.001) and depression (r = 0.341, P = 0.029). Multivariate regression analysis revealed that the odds ratio of RLS, depression, and low serum Alb was 22.900, 42.209, and 0.597, respectively.

CONCLUSIONSThe prevalence of sleep disorders was relatively high in CAPD patients. RLS, depression, and low serum Alb were the risk factors for CAPD patients with sleep disorders.

Adult ; Aged ; Cross-Sectional Studies ; Depressive Disorder ; blood ; complications ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Peritoneal Dialysis ; adverse effects ; Quality of Life ; Restless Legs Syndrome ; blood ; complications ; epidemiology ; Risk Factors ; Serum Albumin ; metabolism ; Sleep Wake Disorders ; blood ; epidemiology ; etiology

The release of hormones and the metabolism of human body are controlled by the circadian rhythm related to sleep-wake cycle. Growth hormone, prolactin, thyroid stimulating hormone, cortisol, glucose, and insulin-secretion rates fluctuate according to the sleep-wake cycle. In addition, sleep is related to the appetite regulation and carbohydrate and other energy metabolism. Hypocretin (orexin), an excitatory neuropeptide, regulates waking and diet intake, and the poor sleep increases diet intake. The short sleep duration increases one's body mass index and impairs the function of the endocrine and metabolism, causing increases in the risk of glucose intolerance and diabetes. The poor sleep quality and sleep disorders have similar impact on the metabolic function. In short, the sleep loss and the poor quality of sleep have a detrimental effect on the endocrine and energy metabolism. The improvement of sleep quality by the future research and appropriate clinical treatment would contribute to the decrease of the metabolic diseases such as diabetes.
Appetite Regulation ; Body Mass Index ; Circadian Rhythm ; Diet ; Energy Metabolism ; Glucose ; Glucose Intolerance ; Growth Hormone ; Human Body ; Hydrocortisone ; Intracellular Signaling Peptides and Proteins ; Metabolic Diseases ; Neuropeptides ; Prolactin ; Sleep Wake Disorders ; Thyrotropin ; Orexins

Sleep and public health has close relationship. Life in modern society makes human sleep deprived state. Sleep deprivation could induce cognitive deficits, heart diseases, glucose metabolic disorders, and decrease quality of life. Moreover, shift worker should work in mismatched circadian rhythm environment. Errors due to sleep deprivation, mismatched circadian rhythm, and various sleep disorders including sleep apnea could be tremendous hazard to public. By understanding sleep physiology, we can prevent sleep deprivation induced accidents and health problems. Sleep specialists have role of education and detection of patients with sleep disorders
Circadian Rhythm ; Glucose Metabolism Disorders ; Heart Diseases ; Humans ; Public Health ; Quality of Life ; Sleep Apnea Syndromes ; Sleep Deprivation ; Sleep Wake Disorders ; Specialization

OBJECTIVEMeasuring the serum concentrations of adrenocorticotropic hormone (ACTH) and cortisol in epileptic seizures during sleep to investigate their link to the EEG changes.

METHODSPre-surgical evaluation was performed by video-EEG monitoring using 24 channel recording. Thirty six epilepsy patients could be attributed to two groups: 28 patients had spontaneous seizures, and the other 8 patients whose seizures were induced by bemegride. Another 11 persons with confirmed psychogenic non-epileptic seizures (PNES) served as control group. Blood samples were obtained at five points: wake (08:00 a.m.), sleep (00:00 a.m.), and shortly before, during and after an epileptic seizure. The serum ACTH and cortisol were measured and analyzed by chemiluminescent immunoassay.

RESULTSThe levels of ACTH and cortisol in serum underwent significant changes: declining below the average sleep-level shortly before seizures, increasing during seizures, and far above the average wake-level after seizures (P < 0.001). Such changes did not occur in the control group (P > 0.05). The ACTH and cortisol levels had no significant difference between spontaneous group and bemegride-induced group (P > 0.05).

CONCLUSIONThe serum concentrations of ACTH and cortisol during sleep seizures are linked with pre-ictal and ictal EEG changes in epilepsy patients.

Action Potentials ; physiology ; Adolescent ; Adrenocorticotropic Hormone ; blood ; Adult ; Bemegride ; pharmacology ; Biomarkers ; blood ; Cerebral Cortex ; metabolism ; physiopathology ; Convulsants ; pharmacology ; Electroencephalography ; Epilepsy ; blood ; physiopathology ; Evoked Potentials ; physiology ; Humans ; Hydrocortisone ; blood ; Hypothalamo-Hypophyseal System ; metabolism ; physiopathology ; secretion ; Pituitary-Adrenal System ; metabolism ; physiopathology ; secretion ; Sleep Wake Disorders ; blood ; physiopathology ; Up-Regulation ; physiology ; Wakefulness ; physiology

The paper summarized the sedative pharmacological effects of CMM, which were reported in the past 10 years. Those sedative CMMs were found in several type of Chinese medicine, such as tranquilizing the mind, calming the liver to stop the wind, general tonic, blood-activating and stasis-resolving drugs, heat-clearing drugs, exterior-releasing drugs, drugs for resuscitation, diuresis-inducing and dampness-draining drugs, ect. Out of them, the general tonic drugs were used in many occasions. Two Chinese herbs, jujube seed and polygala were used popularly as sedative drugs. And their effects have something to do with heart Meridian and liver Meridian. The Locomotor activity, sleeping test and forcing swimming were used commonly to detect the sedative effects. The sedative mechanisms of those CMM were related with neuro-transmitters such as Dopamine (DA), 5-HT and gamma-GABA, etc.
Animals ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Hypnotics and Sedatives ; pharmacology ; therapeutic use ; Materia Medica ; pharmacology ; therapeutic use ; Medicine, Chinese Traditional ; Neurotransmitter Agents ; metabolism ; Sleep Wake Disorders ; drug therapy ; metabolism ; Tranquilizing Agents ; pharmacology ; therapeutic use