Gut microbiome is indispensable for maintaining normal brain function.Specifically,gut microbiota plays a causal role in sleep deprivation(SD)-induced cognitive impairment.In this study,neurobehavioral effects of the ...Gut microbiome is indispensable for maintaining normal brain function.Specifically,gut microbiota plays a causal role in sleep deprivation(SD)-induced cognitive impairment.In this study,neurobehavioral effects of the Bifidobacterium breve strain(CCFM1025)were assessed in sleep-deprived mice.CCFM1025 improved the body weight and food and water intake of the mice.It also alleviated SD-induced cognitive behavioural abnormalities(in the novel object recognition test),but did not show beneficial effects on mood-and spatial memory-related behaviours.CCFM1025 significantly altered the gut microbial composition and genome function.Key microbial metabolites that may regulate sleep function were also identified,such as isovaleric acid andγ-aminobutyric acid in the gut and purine metabolites in the serum.Those metabolites may participate in gutbrain communication by acting on the striatal melatonin system,for example to increase melatonin levels,and by regulating the expression of circadian clock genes such as those encoding the adenosine A2A receptor and period circadian regulator 1.Collectively,administration of probiotics alleviated cognitive impairment and circadian rhythm disturbance induced by SD via modulation of gut microbiome and its metabolites.These findings may help guide the treatment of insomnia or other sleep disorders via dietary strategies.展开更多
Objective To observe the effect of application of garlic paste at Shenque (神阙 CV8) on the circadian rhythm in sleep deprivation young students. Metheds Twenty healthy volunteer young male students from Southern Me...Objective To observe the effect of application of garlic paste at Shenque (神阙 CV8) on the circadian rhythm in sleep deprivation young students. Metheds Twenty healthy volunteer young male students from Southern Medical University were randomly divided into three groups: normal group (A), sleep deprivation group (B) and treatment group (C). Volunteers in group B and C received 48 h sleep deprivation (SD), and in the mean time volunteers in group C were treated by garlic paste at Shenque (神阙 CV8), while those in group A had no any treatment. The body temperature of all the volunteers was detected at 6:00 am, 12:00 am, 6:00 pm and 0:00 am, respectively, after the treatment. Results The mean body temperature values in group A and C both were highest at 6: 00 pm and lowest at 6: 00 am which had a significant difference in each group (P〈0.01); in group B, the mean body temperature was highest at 0:00 am and lowestat 6:00 am, no significant difference was found between them (P〉0.05). Results of cosine analysis showed that in subjects of group B the circadian rhythm of body temperature still kept going well after SD, but the peak amplitude and amplitude of vibration were higher than those of group A, and the acrophase of group B was obviously lower than that of group C and A. The 3 indexes of group C were similar to those of group A, denoting that garlic paste application of Shenque (神阙 CV8) could prevent disorders of circadian rhythm of the body temperature. Conclusion The garlic paste application at Shenque (神阙 CV8) can adjust circadian rhythm and accelerate the recovery processes of circadian rhythm in SD young students.展开更多
Objective To explore the changes in plasma angiotensin II (Ang Ⅱ) and circadian rhythm of blood pressure among hypertensive patients with sleep apnea syndrome (SAS) before and after continuous positive airway pre...Objective To explore the changes in plasma angiotensin II (Ang Ⅱ) and circadian rhythm of blood pressure among hypertensive patients with sleep apnea syndrome (SAS) before and after continuous positive airway pressure (CPAP) or surgical treatment. Methods A total of 180 essential hypertension patients were enrolled in our study. The determination of plasma Ang Ⅱ concentration, ambulatory blood pressure (ABP), and polysomnography (PSG) monitoring were performed before and 3 months after CPAP or surgical treatment. Results Patients were classified into three groups by their apnea-hypopnea index (AHI): essential hypertension group (EH group, n=72; AHI〈5), essential hypertension with mild SAS group (EH+mild SAS group, n=60, 5≤AHI〈20), and essential hypertension with moderate and severe SAS group (EH+moderate-severe SAS group, n=48, AHI_〉20). The concentrations of plasma AngⅡ in the above three groups were 13.42±3.27, 16.17±3.82, and 18.73±4.05 ng/mL respectively before treatment, and AngⅡ concentration in EH patients combined with SAS was significantly higher than that in EH group (all P〈0.05). After treatment the values in the latter two groups significantly decreased to 14.67±2.56 and 15.03±3.41 ng/mL respectively (P〈0.05). The incidence of non-dipper blood pressure curve in EH patients was 31.9%, and those in hypertensive patients with mild SAS and moderate-severe SAS were 51.7% and 58.3%, respectively before treatment. The incidence of non-dipper blood pressure curve in the EH patients with mild SAS was significantly higher than that of patients with EH alone (P〈0.05). After CPAP treatment or surgery, the incidence of non-dipper blood pressure curve in the two SAS groups was significantly decreased to 38.3% and 39.6%, respectively (P〈0.05). Conclusions Ang Ⅱ might play a role in blood pressure variability in patients with obstructive SAS. CPAP or surgical treatment can improve blood pressure disorder and decrease plasma Ang Ⅱ level in patients with obstructive SAS.展开更多
Sleep disorders are common in patients with Alzheimer’s disease,and can even occur in patients with amnestic mild cognitive impairment,which appears before Alzheimer’s disease.Sleep disorders further impair cognitiv...Sleep disorders are common in patients with Alzheimer’s disease,and can even occur in patients with amnestic mild cognitive impairment,which appears before Alzheimer’s disease.Sleep disorders further impair cognitive function and accelerate the accumulation of amyloid-βand tau in patients with Alzheimer’s disease.At present,sleep disorders are considered as a risk factor for,and may be a predictor of,Alzheimer’s disease development.Given that sleep disorders are encountered in other types of dementia and psychiatric conditions,sleep-related biomarkers to predict Alzheimer’s disease need to have high specificity and sensitivity.Here,we summarize the major Alzheimer’s disease-specific sleep changes,including abnormal non-rapid eye movement sleep,sleep fragmentation,and sleep-disordered breathing,and describe their ability to predict the onset of Alzheimer’s disease at its earliest stages.Understanding the mechanisms underlying these sleep changes is also crucial if we are to clarify the role of sleep in Alzheimer’s disease.This paper therefore explores some potential mechanisms that may contribute to sleep disorders,including dysregulation of the orexinergic,glutamatergic,andγ-aminobutyric acid systems and the circadian rhythm,together with amyloid-βaccumulation.This review could provide a theoretical basis for the development of drugs to treat Alzheimer’s disease based on sleep disorders in future work.展开更多
Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morb...Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease(CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD.展开更多
Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a r...Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a rat model of HIBD,up-regulation of microRNA-325(miR-325)in the pineal gland is responsible for the suppression of Aanat,a key enzyme involved in melatonin synthesis and circadian rhythm regulation.To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD,we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University(Dushuhu Branch)in 2019.We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD.Furthermore,a luciferase reporter gene assay revealed that LIM homeobox 3(LHX3)is a novel downstream target of miR-325.In addition,in miR-325 knock-down mice,the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland.We established a neonatal mouse model of HIBD by performing doublelayer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours.Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions.Finally,we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3.Taken together,our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD.The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University(approval No.2015028)on July 20,2015.Animal experiments were approved by Animal Care and Use Committee,School of Medicine,Soochow University,China(approval No.XD-2016-1)on January 15,2016.展开更多
The neuropsychiatric disease named obsessive-compulsive disorder is composed by obsessions and/or compulsions.Obsessive-compulsive disorder etiologies are undefined.However,numerous mechanisms in several localizations...The neuropsychiatric disease named obsessive-compulsive disorder is composed by obsessions and/or compulsions.Obsessive-compulsive disorder etiologies are undefined.However,numerous mechanisms in several localizations are implicated.Some studies showed that both glutamate,inflammatory factors and oxidative stress could have main functions in obsessive-compulsive disorder.Glycogen synthase kinase-3β,the major negative controller of the WNT/β-catenin pathway is upregulated in obsessive-compulsive disorder.In obsessive-compulsive disorder,some studies presented the actions of the different circadian clock genes.WNT/β-catenin pathway and circadian clock genes appear to be intricate.Thus,this review focuses on the interaction between circadian clock genes and the WNT/β-catenin pathway in obsessive-compulsive disorder.展开更多
Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases and can occur at multiple levels.Accumulating evidence reveals a bidirectional relationship between disruptions of circadia...Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases and can occur at multiple levels.Accumulating evidence reveals a bidirectional relationship between disruptions of circadian rhythms and sleep cycles and neurodegenerative diseases.Circadian disruption and sleep disorders aggravate neurodegeneration and neurodegenerative diseases can in turn disrupt circadian rhythms and sleep.Importantly,circadian disruption and various sleep disorders can increase the risk of neurodegenerative diseases.Thus,harnessing the circadian biology findings from preclinical and translational research in neurodegenerative diseases is of importance for reducing risk of neurodegeneration and improving symptoms and quality of life of individuals with neurodegenerative disorders via approaches that normalize circadian in the context of precision medicine.In this review,we discuss the implications of circadian disruption and sleep disorders in neurodegenerative diseases by summarizing evidence from both human and animal studies,focusing on the bidirectional links of sleep and circadian rhythms with prevalent forms of neurodegeneration.These findings provide valuable insights into the pathogenesis of neurodegenerative diseases and suggest a promising role of circadian-based interventions.展开更多
Background Obstructive sleep apnea syndrome (OSAS) is strongly associated with obesity and with cardiovascular disease.Ghrelin and obestatin are two peptides from the same source but have opposite roles.Both of them...Background Obstructive sleep apnea syndrome (OSAS) is strongly associated with obesity and with cardiovascular disease.Ghrelin and obestatin are two peptides from the same source but have opposite roles.Both of them can affect feeding and regulate vascular tune.The aim of this study was to investigate the relationship between plasma ghrelin,obestatin,the ratio of ghrelin and obestatin (G/O) and sleep parameters and blood pressure circadian rhythms in patients with OSAS.Methods This study enrolled 95 newly diagnosed over-weight OSAS patients (OSAS group),30 body mass index (BMI)-match non-OSAS adults (over-weight group) and 30 non-OSAS normal weight adults (control group).Polysomnography (PSG) was performed in the OSAS group and over-weight group.Blood pressure of all subjects was monitored by means of 24-hour ambulatory blood pressure monitoring.The concentration of plasma ghrelin and obestatin was detected by enzyme-linked immunosorbent assay (ELISA).Results Plasma ghrelin levels in the OSAS group and over-weight group were significantly lower than that of the control group (P <0.05).Plasma obestatin levels were lower in the over-weight group and OSAS group,but there was no significant difference among the three groups.The blood pressure in OSAS patients was higher,and there was a significant difference in all blood pressure parameters compared to the control group,and in the daytime average diastolic blood pressure (DBP),nocturnal average systolic blood pressure (SBP) and DBP,DBP variability values as compared to over-weight subjects.Furthermore,there were significantly more non-dipper patterns of blood pressure (including hypertension and normotension) in the OSAS group than in the other two groups (P <0.01).Correlation analysis showed that ghrelin levels had a significant correlation with BMI and nocturnal average DBP but not with PSG parameters.In contrast,the G/O ratio had a negative correlation with apnea-hypopnea index (AHI) (P <0.05),as well as a strong positive correlation with the blood pressure variability values (P <0.01).In multivariate analyses,AHI (P <0.05) and G/O (P <0.05)were independently related to SBP variability changes,while AHI (P <0.05),G/O (P <0.01) and BMI (P <0.05) were independently related to DBP variability changes.Conclusions Our data show plasma ghrelin and obestatin levels were related to obesity in OSAS.Sleep apnea in OSAS patients could have led to an imbalance in G/O in the basis of obesity.Moreover,the imbalance may promote nighttime blood pressure elevation and affect blood pressure circadian disorder.展开更多
OBJECTIVE Obstructive sleep apnea(OSA)is a potential cardiovascular risk.We aimed to investigate the association of OSA with heart rhythm disorders and prognosis in elderly patients with new-onset acute myocardial inf...OBJECTIVE Obstructive sleep apnea(OSA)is a potential cardiovascular risk.We aimed to investigate the association of OSA with heart rhythm disorders and prognosis in elderly patients with new-onset acute myocardial infarction(AMI).METHODS We prospectively enrolled 252 AMI elderly patients(mean age,68.5±6.9 years)who were undergoing revascularization and completed a sleep study during their hospitalization.All subjects were categorized into non-OSA(apnea–hypopnea index(AHI)<15,n=130)and OSA(AHI≥15,n=122)groups based on the AHI.The changes in the autonomic nervous system,incidence of arrhythmia during nocturnal sleep,and major adverse cardiovascular and cerebrovascular events(MACCEs)were compared between the groups.RESULTS The mean AHI value in all AMI patients was 22.8±10.9.OSA patients showed higher levels of body mass index and peak high-sensitivity C-reactive protein and lower levels of minimum nocturnal oxygen saturation(Min Sa O2),as well as greater proportion of multivessel coronary artery disease(all P<0.05).The OSA group also showed significant increases in heart rate variability and heart rate turbulence onset(both P<0.05)and higher incidence of arrhythmia(including sinus,atrial,and ventricular in origin).At a median follow-up of 6 months(mean 0.8–1.6 years),OSA(AHI≥15)combined with hypoxia(Min Sa O2≤80%)was independently associated with the incidence of MACCEs(hazard ratio[HR]:4.536;95%confidence interval[CI]:1.461-14.084,P=0.009)after adjusting for traditional risk factors.CONCLUSIONS OSA and OSA-induced hypoxia may correlate with the severity of myocardial infarction,increase the occurrence of heart rhythm disorders in elderly subacute MI patients,and worsen their short-term poor outcomes.展开更多
Parkinson’s disease(PD)is the second most common neurodegenerative disease,which manifests with both motor and non-motor symptoms.Circadian rhythm dysregulation,as one of the most challenging non-motor features of PD...Parkinson’s disease(PD)is the second most common neurodegenerative disease,which manifests with both motor and non-motor symptoms.Circadian rhythm dysregulation,as one of the most challenging non-motor features of PD,usually appears long before obvious motor symptoms.Moreover,the dysregulated circadian rhythm has recently been reported to play pivotal roles in PD pathogenesis,and it has emerged as a hot topic in PD research.In this review,we briefly introduce the circadian rhythm and circadian rhythm-related genes,and then summarize recent research progress on the altered circadian rhythm in PD,ranging from clinical features to the possible causes of PD-related circadian disorders.We believe that future comprehensive studies on the topic may not only help us to explore the mechanisms of PD,but also shed light on the better management of PD.展开更多
Ⅰ. INTRODUCTIONIt has recently been known that the endogenous sleep-inducing neuropeptide Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu has both sleep-inducing and circadian rhythm programming effects. The time of efficacy of ...Ⅰ. INTRODUCTIONIt has recently been known that the endogenous sleep-inducing neuropeptide Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu has both sleep-inducing and circadian rhythm programming effects. The time of efficacy of the former is not long, no more than 1—2h according to most authors, whereas the latter can be effective throughout 24h. Until now, most studies are concerned with the former and only a little information is available展开更多
Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the ...Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson's disease (PD) exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative conse- quences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.展开更多
The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth's environment, ...The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth's environment, which is characterized by a 24-hour light–dark cycle. Changes in gravity load, lighting and work schedules during spaceflight missions can impact circadian clocks and disrupt sleep, in turn jeopardizing the mood, cognition and performance of orbiting astronauts. In this review, we summarize our understanding of both the influence of the space environment on the circadian timing system and sleep and the impact of these changes on astronaut physiology and performance.展开更多
Attention deficit hyperactivity disorder(ADHD)is one of the most prevalent psychiatric disorders in children,and ADHD patients always display circadian abnormalities.While,the ADHD drugs currently used in clinic have ...Attention deficit hyperactivity disorder(ADHD)is one of the most prevalent psychiatric disorders in children,and ADHD patients always display circadian abnormalities.While,the ADHD drugs currently used in clinic have strong side effects,such as psychosis,allergic reactions,and heart problems.Here,we demonstrated carbon dots derived from the ascorbic acid(VCDs)could strongly rescue the hyperactive and impulsive behaviour of a zebrafish ADHD disease model caused by per1b mutation.VCDs prolonged the circadian period of zebrafish for more than half an hour.In addition,the amplitude and circadian phase were also changed.The dopamine level was specifically increased,which may be caused by stimulation of the dopaminergic neuron development in the midbrain.Notably,it was found that the serotonin level was not altered by VCDs treatments.Also,the gene transcriptome effects of VCDs were discussed in present work.Our results provided the dynamic interactions of carbon dots with circadian system and dopamine signaling pathway,which illustrates a potential application of degradable and bio-safe VCDs for the treatment of the attention deficient and hyperactive disorder through circadian intervention.展开更多
Evidence about the interaction between circadian rhythms(CR)and epilepsy has been expanded with the application of advanced detection technology.An adequate understanding of how circadian system and epilepsy interact ...Evidence about the interaction between circadian rhythms(CR)and epilepsy has been expanded with the application of advanced detection technology.An adequate understanding of how circadian system and epilepsy interact with each other could contribute to more accurate seizure prediction as well as rapid development of potential treatment timed to specific phases of CR.In this review,we present the reciprocal relationship between CR and epileptic activities from aspects of sleep effect,genetic modulation and brain biochemistry.It has been found that sleep-wake patterns,circadian timing systems and multidien rhythms have essential roles in seizure activities and interictal epileptiform discharge(IED).For instance,specific distribution patterns of seizures and IED have been reported,i.e.,lighter non-rapid eye movement(NREM)sleep stage(stage 2)induces seizures while deeper NREM sleep stage(stage 3)activates IEDs.Furthermore,the epilepsy type,seizure type and seizure onset zone can significantly affect the rhythms of seizure occurrence.Apart from the common seizure types,several specific epilepsy syndromes also have a close correlation with sleep-wakefulness patterns.Sleep influences the epilepsy rhythm,and conversely,epilepsy alters the sleep rhythm through multiple pathways.Clock genes accompanied by two feedback loops of regulation have an important role in cortical excitability and seizure occurrence,which may be involved in the mTORopathy.The suprachiasmatic nuclei(SCN)has a rhythm of melatonin and cortisol secretion under the circadian pattern,and then these hormones can feed back into a central oscillator to affect the SCN-dependent rhythms,leading to variable but prominent influence on epilepsy.Furthermore,we discuss the precise predictive algorithms and chronotherapy strategies based on different temporal patterns of seizure occurrence for patients with epilepsy,which may offer a valuable indication for non-invasive closed-loop treatment system.Optimization of the time and dose of antiseizure medications,and resynchronization of disturbed CR(by hormone therapy,light exposure,ketogenic diet,novel small molecules)would be beneficial for epileptic patients in the future.Before formal clinical practice,future large-scale studies are urgently needed to assist prediction and treatment of circadian seizure activities and address unsolved restrictions.展开更多
Objective: The objective is to observe the treatment effect of electro-acupuncture (EA) on core circadian clock gene Per2 and Bmal1 expression in hypothalamus of sleep-deprivation (SD) rats. Methods: Thirty-two Wistar...Objective: The objective is to observe the treatment effect of electro-acupuncture (EA) on core circadian clock gene Per2 and Bmal1 expression in hypothalamus of sleep-deprivation (SD) rats. Methods: Thirty-two Wistar male rats were randomly divided into 4 groups. Mice in the blank control group did not receive any treatment;the remaining groups were applied with para-chlorophenylalanine (PCPA) 300 mg/kg intraperitoneal injection for 2 days. Diazepam group received intraperitoneal injection of Diazepam (0.9 mg/kg, i.p.) one time a day for 5 days, while M group was treated with saline (0.9 mg/kg, i.p.) at the same time. Rats in EA group were given EA treatment, 20 minutes, once a day for 5 days, and rats in remaining groups were put into fixation-machine for the same time everyday, lasting for 5 days. Rats were sacrificed after anesthesia at the 8th day. Real-time PCR was adopted to detect the expression in clock gene Per2 and Bmal1 of each group. Results: Compared with blank control group, the expression of Per2 was significant decreased in PCPA model group (P 0.05). Conclusion: EA can significant up-regulate the expression of Per2 in SD rats, and down-regulate gene Bmal1 expression, and benefiting the weight of rats. Thus, EA is a potentially promising intervention to treat sleep-deprivation.展开更多
Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep...Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability,slower response times and performance detriments.Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health,economic consequences,and most importantly increased all-cause mortality.Several research studies support the associations among sleep,immune function and inflammation.Here,we review the current research linking sleep,immune function,and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders.Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep.The inflammatory cytokines such as tumor necrosis factor,interleukin-1(IL-1),and IL-6 have been shown to be a significant contributor of sleep disturbances.On the other hand,sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines.Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease,gastro-esophageal reflux,liver disorders and colorectal cancer.In turn,abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases.Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.展开更多
Sleep-wake rhythm disturbances,which are characterized by abnormal sleep timing or duration,are associated with cognitive dysfunction.Photoacoustic treatments including light and sound stimulation have been found to b...Sleep-wake rhythm disturbances,which are characterized by abnormal sleep timing or duration,are associated with cognitive dysfunction.Photoacoustic treatments including light and sound stimulation have been found to be effective in modulating sleep patterns and improving cognitive behavior in abnormal sleep-wake pattern experiments.In this study,we examined whether light and sound interventions could reduce sleep-wake pattern disturbances and memory deficits in a sleep rhythm disturbance model.We established a model of sleep rhythm disturbance in C57 BL/6 J mice via a sleep deprivation method involving manual cage tapping,cage jostling,and nest disturbance.We used a Mini Mitter radio transmitter device to monitor motor activity in the mice and fear conditioning tests to assess cognitive function.Our results indicated that an intervention in which the mice were exposed to blue light(40-Hz flickering frequency)for 1 hour during their subjective daytime significantly improved the 24-hour-acrophase shift and reduced the degree of memory deficit induced by sleep deprivation.However,interventions in which the mice were exposed to a 40-Hz blue light at offset time or subjective night time points,as well as 2 Hz-blue light at 3 intervention time points(subjective day time,subjective night time,and offset time points),had no positive effects on circadian rhythm shift or memory deficits.Additionally,a 2000-Hz sound intervention during subjective day time attenuated the24-hour-acrophase shift and memory decline,while 440-Hz and 4000-Hz sounds had no effect on circadian rhythms.Overall,these results demonstrate that photoacoustic treatment effectively corrected abnormal sleep-wake patterns and cognitive dysfunction associated with sleep-deprivation-induced disturbances in sleep-wake rhythm.All animal experiments were approved by the Experimental Animal Ethics Committee of Drum Tower Hospital Affiliated to the Medical College of Nanjing University,China(approval No.20171102)on November20,2017.展开更多
基金the financial support from Natural Science Foundation of Jiangsu Province(BK20210456)the National Natural Science Foundation of China(32201988,31972052,32021005,31820103010)+4 种基金the Fundamental Research Funds for the Central Universities(JUSRP22006,JUSRP51501)the China National Postdoctoral Program for Innovative Talents(BX2021114)China Postdoctoral Science Foundation(2021M691290)the Postdoctoral Science Foundation of Jiangsu Province(2021K127B)the Program of Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu Province。
文摘Gut microbiome is indispensable for maintaining normal brain function.Specifically,gut microbiota plays a causal role in sleep deprivation(SD)-induced cognitive impairment.In this study,neurobehavioral effects of the Bifidobacterium breve strain(CCFM1025)were assessed in sleep-deprived mice.CCFM1025 improved the body weight and food and water intake of the mice.It also alleviated SD-induced cognitive behavioural abnormalities(in the novel object recognition test),but did not show beneficial effects on mood-and spatial memory-related behaviours.CCFM1025 significantly altered the gut microbial composition and genome function.Key microbial metabolites that may regulate sleep function were also identified,such as isovaleric acid andγ-aminobutyric acid in the gut and purine metabolites in the serum.Those metabolites may participate in gutbrain communication by acting on the striatal melatonin system,for example to increase melatonin levels,and by regulating the expression of circadian clock genes such as those encoding the adenosine A2A receptor and period circadian regulator 1.Collectively,administration of probiotics alleviated cognitive impairment and circadian rhythm disturbance induced by SD via modulation of gut microbiome and its metabolites.These findings may help guide the treatment of insomnia or other sleep disorders via dietary strategies.
文摘Objective To observe the effect of application of garlic paste at Shenque (神阙 CV8) on the circadian rhythm in sleep deprivation young students. Metheds Twenty healthy volunteer young male students from Southern Medical University were randomly divided into three groups: normal group (A), sleep deprivation group (B) and treatment group (C). Volunteers in group B and C received 48 h sleep deprivation (SD), and in the mean time volunteers in group C were treated by garlic paste at Shenque (神阙 CV8), while those in group A had no any treatment. The body temperature of all the volunteers was detected at 6:00 am, 12:00 am, 6:00 pm and 0:00 am, respectively, after the treatment. Results The mean body temperature values in group A and C both were highest at 6: 00 pm and lowest at 6: 00 am which had a significant difference in each group (P〈0.01); in group B, the mean body temperature was highest at 0:00 am and lowestat 6:00 am, no significant difference was found between them (P〉0.05). Results of cosine analysis showed that in subjects of group B the circadian rhythm of body temperature still kept going well after SD, but the peak amplitude and amplitude of vibration were higher than those of group A, and the acrophase of group B was obviously lower than that of group C and A. The 3 indexes of group C were similar to those of group A, denoting that garlic paste application of Shenque (神阙 CV8) could prevent disorders of circadian rhythm of the body temperature. Conclusion The garlic paste application at Shenque (神阙 CV8) can adjust circadian rhythm and accelerate the recovery processes of circadian rhythm in SD young students.
文摘Objective To explore the changes in plasma angiotensin II (Ang Ⅱ) and circadian rhythm of blood pressure among hypertensive patients with sleep apnea syndrome (SAS) before and after continuous positive airway pressure (CPAP) or surgical treatment. Methods A total of 180 essential hypertension patients were enrolled in our study. The determination of plasma Ang Ⅱ concentration, ambulatory blood pressure (ABP), and polysomnography (PSG) monitoring were performed before and 3 months after CPAP or surgical treatment. Results Patients were classified into three groups by their apnea-hypopnea index (AHI): essential hypertension group (EH group, n=72; AHI〈5), essential hypertension with mild SAS group (EH+mild SAS group, n=60, 5≤AHI〈20), and essential hypertension with moderate and severe SAS group (EH+moderate-severe SAS group, n=48, AHI_〉20). The concentrations of plasma AngⅡ in the above three groups were 13.42±3.27, 16.17±3.82, and 18.73±4.05 ng/mL respectively before treatment, and AngⅡ concentration in EH patients combined with SAS was significantly higher than that in EH group (all P〈0.05). After treatment the values in the latter two groups significantly decreased to 14.67±2.56 and 15.03±3.41 ng/mL respectively (P〈0.05). The incidence of non-dipper blood pressure curve in EH patients was 31.9%, and those in hypertensive patients with mild SAS and moderate-severe SAS were 51.7% and 58.3%, respectively before treatment. The incidence of non-dipper blood pressure curve in the EH patients with mild SAS was significantly higher than that of patients with EH alone (P〈0.05). After CPAP treatment or surgery, the incidence of non-dipper blood pressure curve in the two SAS groups was significantly decreased to 38.3% and 39.6%, respectively (P〈0.05). Conclusions Ang Ⅱ might play a role in blood pressure variability in patients with obstructive SAS. CPAP or surgical treatment can improve blood pressure disorder and decrease plasma Ang Ⅱ level in patients with obstructive SAS.
基金This work was funded by the National Natural Science Foundation of China, Nos. 81660151 (to FFH), 81660751 (to SLY).
文摘Sleep disorders are common in patients with Alzheimer’s disease,and can even occur in patients with amnestic mild cognitive impairment,which appears before Alzheimer’s disease.Sleep disorders further impair cognitive function and accelerate the accumulation of amyloid-βand tau in patients with Alzheimer’s disease.At present,sleep disorders are considered as a risk factor for,and may be a predictor of,Alzheimer’s disease development.Given that sleep disorders are encountered in other types of dementia and psychiatric conditions,sleep-related biomarkers to predict Alzheimer’s disease need to have high specificity and sensitivity.Here,we summarize the major Alzheimer’s disease-specific sleep changes,including abnormal non-rapid eye movement sleep,sleep fragmentation,and sleep-disordered breathing,and describe their ability to predict the onset of Alzheimer’s disease at its earliest stages.Understanding the mechanisms underlying these sleep changes is also crucial if we are to clarify the role of sleep in Alzheimer’s disease.This paper therefore explores some potential mechanisms that may contribute to sleep disorders,including dysregulation of the orexinergic,glutamatergic,andγ-aminobutyric acid systems and the circadian rhythm,together with amyloid-βaccumulation.This review could provide a theoretical basis for the development of drugs to treat Alzheimer’s disease based on sleep disorders in future work.
基金Supported by a NIH grant to Dr.Cukor(MD006875)(in part)
文摘Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease(CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD.
基金This study was supported by the National Natural Science Foundation of China,Nos.81871193(to XD),81671532(to BS),81771625&81701490(to XF),81801505(to MG)Jiangsu Provincial Medical Youth Talent of China,Nos.QNRC2016763(to XD),QNRC2016758(to LXX),QNRC2016762(to ML)+7 种基金the Science and Technology Project of Suzhou City of China,No.SS201709(to XD)the Natural Science Foundation of Jiangsu Province of China,No.BK20180205(to XD)the Training Program Foundation for Health Talents of Gusu of China,No.GSWS2019049(to XD)the Jiangsu Provincial Key Medical Discipline of China,No.ZDXKA2016013(to XF)the Jiangsu Province Women and Children Health Research Project of China,No.F201750(to LXX)the Pediatric Clinical Center of Suzhou City of China,No.Szzx201504(to XF)Suzhou Industrial Technology Innovation Project of China,No.SYS201765(to LZ)the Project of Suzhou Science,Education and Health and Technology,China,No.KJXW2018018(to ML).
文摘Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a rat model of HIBD,up-regulation of microRNA-325(miR-325)in the pineal gland is responsible for the suppression of Aanat,a key enzyme involved in melatonin synthesis and circadian rhythm regulation.To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD,we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University(Dushuhu Branch)in 2019.We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD.Furthermore,a luciferase reporter gene assay revealed that LIM homeobox 3(LHX3)is a novel downstream target of miR-325.In addition,in miR-325 knock-down mice,the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland.We established a neonatal mouse model of HIBD by performing doublelayer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours.Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions.Finally,we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3.Taken together,our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD.The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University(approval No.2015028)on July 20,2015.Animal experiments were approved by Animal Care and Use Committee,School of Medicine,Soochow University,China(approval No.XD-2016-1)on January 15,2016.
文摘The neuropsychiatric disease named obsessive-compulsive disorder is composed by obsessions and/or compulsions.Obsessive-compulsive disorder etiologies are undefined.However,numerous mechanisms in several localizations are implicated.Some studies showed that both glutamate,inflammatory factors and oxidative stress could have main functions in obsessive-compulsive disorder.Glycogen synthase kinase-3β,the major negative controller of the WNT/β-catenin pathway is upregulated in obsessive-compulsive disorder.In obsessive-compulsive disorder,some studies presented the actions of the different circadian clock genes.WNT/β-catenin pathway and circadian clock genes appear to be intricate.Thus,this review focuses on the interaction between circadian clock genes and the WNT/β-catenin pathway in obsessive-compulsive disorder.
基金funded by the National Natural Science Foundation of China(82071420)the Discipline Construction Program of the Second Affiliated Hospital of Soochow University(XKTJ-XK202001)Suzhou Medical and Health Technology Innovation Project(SKJY2021090).
文摘Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases and can occur at multiple levels.Accumulating evidence reveals a bidirectional relationship between disruptions of circadian rhythms and sleep cycles and neurodegenerative diseases.Circadian disruption and sleep disorders aggravate neurodegeneration and neurodegenerative diseases can in turn disrupt circadian rhythms and sleep.Importantly,circadian disruption and various sleep disorders can increase the risk of neurodegenerative diseases.Thus,harnessing the circadian biology findings from preclinical and translational research in neurodegenerative diseases is of importance for reducing risk of neurodegeneration and improving symptoms and quality of life of individuals with neurodegenerative disorders via approaches that normalize circadian in the context of precision medicine.In this review,we discuss the implications of circadian disruption and sleep disorders in neurodegenerative diseases by summarizing evidence from both human and animal studies,focusing on the bidirectional links of sleep and circadian rhythms with prevalent forms of neurodegeneration.These findings provide valuable insights into the pathogenesis of neurodegenerative diseases and suggest a promising role of circadian-based interventions.
文摘Background Obstructive sleep apnea syndrome (OSAS) is strongly associated with obesity and with cardiovascular disease.Ghrelin and obestatin are two peptides from the same source but have opposite roles.Both of them can affect feeding and regulate vascular tune.The aim of this study was to investigate the relationship between plasma ghrelin,obestatin,the ratio of ghrelin and obestatin (G/O) and sleep parameters and blood pressure circadian rhythms in patients with OSAS.Methods This study enrolled 95 newly diagnosed over-weight OSAS patients (OSAS group),30 body mass index (BMI)-match non-OSAS adults (over-weight group) and 30 non-OSAS normal weight adults (control group).Polysomnography (PSG) was performed in the OSAS group and over-weight group.Blood pressure of all subjects was monitored by means of 24-hour ambulatory blood pressure monitoring.The concentration of plasma ghrelin and obestatin was detected by enzyme-linked immunosorbent assay (ELISA).Results Plasma ghrelin levels in the OSAS group and over-weight group were significantly lower than that of the control group (P <0.05).Plasma obestatin levels were lower in the over-weight group and OSAS group,but there was no significant difference among the three groups.The blood pressure in OSAS patients was higher,and there was a significant difference in all blood pressure parameters compared to the control group,and in the daytime average diastolic blood pressure (DBP),nocturnal average systolic blood pressure (SBP) and DBP,DBP variability values as compared to over-weight subjects.Furthermore,there were significantly more non-dipper patterns of blood pressure (including hypertension and normotension) in the OSAS group than in the other two groups (P <0.01).Correlation analysis showed that ghrelin levels had a significant correlation with BMI and nocturnal average DBP but not with PSG parameters.In contrast,the G/O ratio had a negative correlation with apnea-hypopnea index (AHI) (P <0.05),as well as a strong positive correlation with the blood pressure variability values (P <0.01).In multivariate analyses,AHI (P <0.05) and G/O (P <0.05)were independently related to SBP variability changes,while AHI (P <0.05),G/O (P <0.01) and BMI (P <0.05) were independently related to DBP variability changes.Conclusions Our data show plasma ghrelin and obestatin levels were related to obesity in OSAS.Sleep apnea in OSAS patients could have led to an imbalance in G/O in the basis of obesity.Moreover,the imbalance may promote nighttime blood pressure elevation and affect blood pressure circadian disorder.
基金supported by National Natural Science Youth Fund of China(81100098)Shanghai Municipal Commission of Health and Family Planning for Key Discipline Establishment(2015ZB0503&201840083)Production,Teaching and Research Program for University Teachers in Shanghai(RC20190079)。
文摘OBJECTIVE Obstructive sleep apnea(OSA)is a potential cardiovascular risk.We aimed to investigate the association of OSA with heart rhythm disorders and prognosis in elderly patients with new-onset acute myocardial infarction(AMI).METHODS We prospectively enrolled 252 AMI elderly patients(mean age,68.5±6.9 years)who were undergoing revascularization and completed a sleep study during their hospitalization.All subjects were categorized into non-OSA(apnea–hypopnea index(AHI)<15,n=130)and OSA(AHI≥15,n=122)groups based on the AHI.The changes in the autonomic nervous system,incidence of arrhythmia during nocturnal sleep,and major adverse cardiovascular and cerebrovascular events(MACCEs)were compared between the groups.RESULTS The mean AHI value in all AMI patients was 22.8±10.9.OSA patients showed higher levels of body mass index and peak high-sensitivity C-reactive protein and lower levels of minimum nocturnal oxygen saturation(Min Sa O2),as well as greater proportion of multivessel coronary artery disease(all P<0.05).The OSA group also showed significant increases in heart rate variability and heart rate turbulence onset(both P<0.05)and higher incidence of arrhythmia(including sinus,atrial,and ventricular in origin).At a median follow-up of 6 months(mean 0.8–1.6 years),OSA(AHI≥15)combined with hypoxia(Min Sa O2≤80%)was independently associated with the incidence of MACCEs(hazard ratio[HR]:4.536;95%confidence interval[CI]:1.461-14.084,P=0.009)after adjusting for traditional risk factors.CONCLUSIONS OSA and OSA-induced hypoxia may correlate with the severity of myocardial infarction,increase the occurrence of heart rhythm disorders in elderly subacute MI patients,and worsen their short-term poor outcomes.
基金the National Nature Science Foundation of China(81771521)Key Research and Development Plan of Liaoning Science and Technology Department(2018225051)+1 种基金Guangdong Provincial Key R&D Program(2018B030337001)the National Key Research and Development Program of China(2016YFC1306600).
文摘Parkinson’s disease(PD)is the second most common neurodegenerative disease,which manifests with both motor and non-motor symptoms.Circadian rhythm dysregulation,as one of the most challenging non-motor features of PD,usually appears long before obvious motor symptoms.Moreover,the dysregulated circadian rhythm has recently been reported to play pivotal roles in PD pathogenesis,and it has emerged as a hot topic in PD research.In this review,we briefly introduce the circadian rhythm and circadian rhythm-related genes,and then summarize recent research progress on the altered circadian rhythm in PD,ranging from clinical features to the possible causes of PD-related circadian disorders.We believe that future comprehensive studies on the topic may not only help us to explore the mechanisms of PD,but also shed light on the better management of PD.
文摘Ⅰ. INTRODUCTIONIt has recently been known that the endogenous sleep-inducing neuropeptide Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu has both sleep-inducing and circadian rhythm programming effects. The time of efficacy of the former is not long, no more than 1—2h according to most authors, whereas the latter can be effective throughout 24h. Until now, most studies are concerned with the former and only a little information is available
基金supported by the National Natural Science Foundation of China(81471299)Jiangsu Provincial Special Program of Medical Science(BL2014042)+4 种基金Suzhou Clinical Key Disease Diagnosis and Treatment Technology Foundation(LCZX201304)the Plans for Graduate Research and Innovation in Colleges and Universities of Jiangsu Province,China(KYZZ15_0334)Suzhou Medical Key Discipline Projectthe Priority Academic Program Development of Jiangsu Higher Education Institutions,China(PAPD)Suzhou Clinical Research Center of Neurological Disease(Szzx201503)
文摘Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson's disease (PD) exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative conse- quences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.
基金supported by the National Basic Program of China (2011CB711000 and 2012CB947600)the National Natural Science Foundation of China (31171119, 31171010, 31171049, 31121061, 31271164)Open Fund from Key Laboratory for Space Biosciences & Biotechnology, Northwestern Polytechnical University (2013KF1501)
文摘The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth's environment, which is characterized by a 24-hour light–dark cycle. Changes in gravity load, lighting and work schedules during spaceflight missions can impact circadian clocks and disrupt sleep, in turn jeopardizing the mood, cognition and performance of orbiting astronauts. In this review, we summarize our understanding of both the influence of the space environment on the circadian timing system and sleep and the impact of these changes on astronaut physiology and performance.
基金the National Natural Science Foundation of China(Nos.31671216,81871193,51725204,21771132,51972216,and 52041202)the National MCF Energy R&D Program of China(No.2018YFE0306105)+8 种基金the National Key R&D Program of China(Nos.2020YFA0406104 and 2020YFA0406101)Innovative Research Group Project of the National Natural Science Foundation of China(No.51821002)Natural Science Foundation of Jiangsu Province(No.BK20190041)National College Students Innovation and Entrepreneurship Training Program(No.201710285042Z)Suzhou Scientific Program(No.SS202074)Key R&D program of Ningxia Hui Autonomous Region(No.2022BEG02006)Ningxia Autonomous Region flexible introduction of science and technology innovation team(No.2021RXTDLX08)Agricultural science and technology innovation project of Suzhou Science and Technology Development Plan(No.SNG2020074)Collaborative Innovation Center of Suzhou Nano Science&Technology,the 111 Project,and Suzhou Key Laboratory of Functional Nano&Soft Materials.
文摘Attention deficit hyperactivity disorder(ADHD)is one of the most prevalent psychiatric disorders in children,and ADHD patients always display circadian abnormalities.While,the ADHD drugs currently used in clinic have strong side effects,such as psychosis,allergic reactions,and heart problems.Here,we demonstrated carbon dots derived from the ascorbic acid(VCDs)could strongly rescue the hyperactive and impulsive behaviour of a zebrafish ADHD disease model caused by per1b mutation.VCDs prolonged the circadian period of zebrafish for more than half an hour.In addition,the amplitude and circadian phase were also changed.The dopamine level was specifically increased,which may be caused by stimulation of the dopaminergic neuron development in the midbrain.Notably,it was found that the serotonin level was not altered by VCDs treatments.Also,the gene transcriptome effects of VCDs were discussed in present work.Our results provided the dynamic interactions of carbon dots with circadian system and dopamine signaling pathway,which illustrates a potential application of degradable and bio-safe VCDs for the treatment of the attention deficient and hyperactive disorder through circadian intervention.
基金This work was supported by the Clinical Research Plan of SHDC(SHDC2020CR3066B)。
文摘Evidence about the interaction between circadian rhythms(CR)and epilepsy has been expanded with the application of advanced detection technology.An adequate understanding of how circadian system and epilepsy interact with each other could contribute to more accurate seizure prediction as well as rapid development of potential treatment timed to specific phases of CR.In this review,we present the reciprocal relationship between CR and epileptic activities from aspects of sleep effect,genetic modulation and brain biochemistry.It has been found that sleep-wake patterns,circadian timing systems and multidien rhythms have essential roles in seizure activities and interictal epileptiform discharge(IED).For instance,specific distribution patterns of seizures and IED have been reported,i.e.,lighter non-rapid eye movement(NREM)sleep stage(stage 2)induces seizures while deeper NREM sleep stage(stage 3)activates IEDs.Furthermore,the epilepsy type,seizure type and seizure onset zone can significantly affect the rhythms of seizure occurrence.Apart from the common seizure types,several specific epilepsy syndromes also have a close correlation with sleep-wakefulness patterns.Sleep influences the epilepsy rhythm,and conversely,epilepsy alters the sleep rhythm through multiple pathways.Clock genes accompanied by two feedback loops of regulation have an important role in cortical excitability and seizure occurrence,which may be involved in the mTORopathy.The suprachiasmatic nuclei(SCN)has a rhythm of melatonin and cortisol secretion under the circadian pattern,and then these hormones can feed back into a central oscillator to affect the SCN-dependent rhythms,leading to variable but prominent influence on epilepsy.Furthermore,we discuss the precise predictive algorithms and chronotherapy strategies based on different temporal patterns of seizure occurrence for patients with epilepsy,which may offer a valuable indication for non-invasive closed-loop treatment system.Optimization of the time and dose of antiseizure medications,and resynchronization of disturbed CR(by hormone therapy,light exposure,ketogenic diet,novel small molecules)would be beneficial for epileptic patients in the future.Before formal clinical practice,future large-scale studies are urgently needed to assist prediction and treatment of circadian seizure activities and address unsolved restrictions.
文摘Objective: The objective is to observe the treatment effect of electro-acupuncture (EA) on core circadian clock gene Per2 and Bmal1 expression in hypothalamus of sleep-deprivation (SD) rats. Methods: Thirty-two Wistar male rats were randomly divided into 4 groups. Mice in the blank control group did not receive any treatment;the remaining groups were applied with para-chlorophenylalanine (PCPA) 300 mg/kg intraperitoneal injection for 2 days. Diazepam group received intraperitoneal injection of Diazepam (0.9 mg/kg, i.p.) one time a day for 5 days, while M group was treated with saline (0.9 mg/kg, i.p.) at the same time. Rats in EA group were given EA treatment, 20 minutes, once a day for 5 days, and rats in remaining groups were put into fixation-machine for the same time everyday, lasting for 5 days. Rats were sacrificed after anesthesia at the 8th day. Real-time PCR was adopted to detect the expression in clock gene Per2 and Bmal1 of each group. Results: Compared with blank control group, the expression of Per2 was significant decreased in PCPA model group (P 0.05). Conclusion: EA can significant up-regulate the expression of Per2 in SD rats, and down-regulate gene Bmal1 expression, and benefiting the weight of rats. Thus, EA is a potentially promising intervention to treat sleep-deprivation.
文摘Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability,slower response times and performance detriments.Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health,economic consequences,and most importantly increased all-cause mortality.Several research studies support the associations among sleep,immune function and inflammation.Here,we review the current research linking sleep,immune function,and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders.Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep.The inflammatory cytokines such as tumor necrosis factor,interleukin-1(IL-1),and IL-6 have been shown to be a significant contributor of sleep disturbances.On the other hand,sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines.Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease,gastro-esophageal reflux,liver disorders and colorectal cancer.In turn,abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases.Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.
基金supported by the National Natural Science Foundation of China,No.81730033(to XPG),No.81701371(to TJX),No.81801380(to XZ)the Natural Science Foundation of Jiangsu Province of China,No.BK20170654(to TJX),No.BK20170129(to XZ)the Key Talent’s 13th Five-Year Plan for Strengthening Health of Jiangsu Province of China,No.ZDRCA2016069(to XPG)
文摘Sleep-wake rhythm disturbances,which are characterized by abnormal sleep timing or duration,are associated with cognitive dysfunction.Photoacoustic treatments including light and sound stimulation have been found to be effective in modulating sleep patterns and improving cognitive behavior in abnormal sleep-wake pattern experiments.In this study,we examined whether light and sound interventions could reduce sleep-wake pattern disturbances and memory deficits in a sleep rhythm disturbance model.We established a model of sleep rhythm disturbance in C57 BL/6 J mice via a sleep deprivation method involving manual cage tapping,cage jostling,and nest disturbance.We used a Mini Mitter radio transmitter device to monitor motor activity in the mice and fear conditioning tests to assess cognitive function.Our results indicated that an intervention in which the mice were exposed to blue light(40-Hz flickering frequency)for 1 hour during their subjective daytime significantly improved the 24-hour-acrophase shift and reduced the degree of memory deficit induced by sleep deprivation.However,interventions in which the mice were exposed to a 40-Hz blue light at offset time or subjective night time points,as well as 2 Hz-blue light at 3 intervention time points(subjective day time,subjective night time,and offset time points),had no positive effects on circadian rhythm shift or memory deficits.Additionally,a 2000-Hz sound intervention during subjective day time attenuated the24-hour-acrophase shift and memory decline,while 440-Hz and 4000-Hz sounds had no effect on circadian rhythms.Overall,these results demonstrate that photoacoustic treatment effectively corrected abnormal sleep-wake patterns and cognitive dysfunction associated with sleep-deprivation-induced disturbances in sleep-wake rhythm.All animal experiments were approved by the Experimental Animal Ethics Committee of Drum Tower Hospital Affiliated to the Medical College of Nanjing University,China(approval No.20171102)on November20,2017.