NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.

Alterations of sleep deprivation on brain function:A coordinatebased resting-state functional magnetic resonance imaging metaanalysis

BACKGROUND Sleep deprivation is a prevalent issue that impacts cognitive function.Although numerous neuroimaging studies have explored the neural correlates of sleep loss,inconsistencies persist in the reported results,necessitating an investigation into the consistent brain functional changes resulting from sleep loss.AIM To establish the consistency of brain functional alterations associated with sleep deprivation through systematic searches of neuroimaging databases.Two metaanalytic methods,signed differential mapping(SDM)and activation likelihood estimation(ALE),were employed to analyze functional magnetic resonance imaging(fMRI)data.METHODS A systematic search performed according to PRISMA guidelines was conducted across multiple databases through July 29,2023.Studies that met specific inclusion criteria,focused on healthy subjects with acute sleep deprivation and reported whole-brain functional data in English were considered.A total of 21 studies were selected for SDM and ALE meta-analyses.RESULTS Twenty-one studies,including 23 experiments and 498 subjects,were included.Compared to pre-sleep deprivation,post-sleep deprivation brain function was associated with increased gray matter in the right corpus callosum and decreased activity in the left medial frontal gyrus and left inferior parietal lobule.SDM revealed increased brain functional activity in the left striatum and right central posterior gyrus and decreased activity in the right cerebellar gyrus,left middle frontal gyrus,corpus callosum,and right cuneus.CONCLUSION This meta-analysis consistently identified brain regions affected by sleep deprivation,notably the left medial frontal gyrus and corpus callosum,shedding light on the neuropathology of sleep deprivation and offering insights into its neurological impact.

Regulatory role of CREB/BDNF signaling pathway in acute sleep deprivation-induced anxiety-like behavior mice

Objective:To investigate the regulatory role of cyclic adenosine monophosphate responsive element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway in acute sleep deprivation(SD)-induced anxiety-like behavior mice(SD group)to study the mechanism of anxiety-like behavior better.Methods:The SD chamber was used to deprive the mice of sleep,and the anxiety-like behavior of the mice was verified using an open field test(OFT),elevated plus maze(EPM),forced swim test(FST),and tail suspension test(TST).Finally,proteins were detected by Western blotting.Result:OFT showed that the active distance and the time of stay in the central area were significantly reduced(P<0.05).EPM showed that the time and number of open arms in the SD group were significantly lower than in the control group(P<0.05).The FST showed that the forced swimming immobility time of the SD group was significantly lower than that of the control(P<0.05).Moreover,the TST showed that the immobility time of the tail suspension experiment in the SD group was significantly higher than that in the control group(P<0.05).Conclusion:Acute SD can regulate anxiety-like behavior in mice through the CREB/BDNF signaling pathway.

Overexpression of Sirt6 ameliorates sleep deprivation induced-cognitive impairment by modulating glutamatergic neuron function

Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive behaviors.Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes.The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation(CSD).We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex(PrL).We then assessed cerebral functional connectivity(FC) using resting-state functional MRI,neuron/astrocyte metabolism using a metabolic kinetics analysis;dendritic spine densities using sparse-labeling;and miniature excitato ry postsynaptic currents(mEPSCs) and action potential(AP) firing rates using whole-cell patchclamp recordings.In addition,we evaluated cognition via a comprehensive set of behavioral tests.Compared with controls,Sirt6 was significantly decreased(P<0.05) in the PrL after CSD,accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus,piriform cortex,motor co rtex,somatosensory co rtex,olfactory tubercle,insular cortex,and cerebellum.Sirt6 ove rexpression reve rsed CSD-induced cognitive impairment and reduced FC.Our analysis of metabolic kinetics using [1-13C] glucose and [2-13C] acetate showed that CSD reduced neuronal Glu4and GABA2synthesis,which could be fully restored via forced Sirt6 expression.Furthermore,Sirt6 ove rexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons.These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network,neuronal glucose metabolism,and glutamatergic neurotransmission.Thus,Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.

ADJUSTING EFFECTS OF APPLICATION OF GARLIC PASTE AT SHNQU (神阙 CV8) ON THE CIRCADIAN RHYTHM OF BODY TEMPERATURE INDUCED BY SLEEP DEPRIVATION

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.

Sleep deprivation increase the expression of inducible heat shock protein 70 in rat gastric mucosa

AIM: To investigate if sleep deprivation is able to increase the expression of inducible heat shock protein 70 in gastric mucosa and its possible role in mucosal defense. METHODS: Rats for sleep disruption were placed inside a computerized rotating drum, gastric mucosa was taken from rats with 1, 3 and 7d sleep deprivation. RT-PCR, immunohistochemistry and Western blotting were used to determine the expression of heat shock protein 70. Ethanol (500mL.L(-1), i.g.) was used to induce gastric mucosa damage. RESULTS: RT-PCR, Western blotting and immunostaining confirmed that the sleep deprivation as a stress resulted in significantly greater expression of inducible heat shock protein 70 in gastric mucosa of rats. After the 500mL.L(-1) ethanol challenge, the ulcer area found in the rats with 7d sleep deprivation (19.15 +/- 4.2)mm(2) was significantly lower (P【0.01) than the corresponding control (53.7 +/- 8.1) mm(2). CONCLUSION: Sleep deprivation as a stress, in addition to lowering the gastric mucosal barrier, is able to stimulate the expression of inducible heat shock protein 70 in gastric mucosa of rats, the heat shock protein 70 may play an important role in gastric mucosal protection.

Maternal sleep deprivation induces gut microbial dysbiosis and neuroinflammation in offspring rats

Maternal sleep deprivation(MSD)is a global public health problem that affects the physical and mental development of pregnant women and their newborns.The latest research suggests that sleep deprivation(SD)disrupts the gut microbiota,leading to neuroinflammation and psychological disturbances.However,it is unclear whether MSD affects the establishment of gut microbiota and neuroinflammation in the newborns.In the present study,MSD was performed on pregnant SpragueDawley rats in the third trimester of pregnancy(gestational days 15-21),after which intestinal contents and brain tissues were collected from offspring at different postnatal days(P1,P7,P14,and P56).Based on microbial profiling,microbial diversity and richness increased in pregnant rats subjected to MSD,as reflected by the significant increase in the phylum Firmicutes.In addition,microbial dysbiosis marked by abundant Firmicutes bacteria was observed in the MSD offspring.Furthermore,quantitative real-time polymerase chain reaction(q RT-PCR)and enzyme-linked immunosorbent assay(ELISA)showed that the expression levels of proinflammatory cytokines interleukin 1β(IL-1β)and tumor necrosis factorα(TNF-α)were significantly higher in the MSD offspring at adulthood(P56)than in the control group.Through Spearman correlation analysis,IL-1βand TNF-αwere also shown to be positively correlated with Ruminococcus_1 and Ruminococcaceae_UCG-005 at P56,which may determine the microbiota-host interactions in MSDrelated neuroinflammation.Collectively,these results indicate that MSD changes maternal gut microbiota and affects the establishment of neonatal gut microbiota,leading to neuroinflammation in MSD offspring.Therefore,understanding the role of gut microbiota during physiological development may provide potential interventions for cognitive dysfunction in MSD-impacted offspring.

nfluence of paradoxical sleep deprivation and sleep recovery on testosterone level in rats of different ages

This study was performed to assess serum testosterone alterations induced by paradoxical sleep deprivation （PSD） and to verify their attenuation during sleep recovery （SR） based on different durations and ages. Wistar male rats aged 12 weeks for the younger group and 20 weeks for the elder group were randomly distributed into one of the following groups： a control group （cage and platform）, 3-day SD, 5-day SD, 7-day SD, 1-day SR, 3-day SR and 5-day SR groups. For PSD, the modified multiple platform method was used to specifically limit rapid eye movement （REM） sleep. Differences in the testosterone and luteinizing hormone levels between the younger group and the elder group according to duration of PSD and SR recovery were analysed. Testosterone continued to fall during the sleep deprivation period in a time-dependent manner in both the younger （P=-0.001, correlation coefficient r=-0.651） and elder groups （P=0.001, correlation coefficient r=-0.840）. The elder group showed a significantly lower level of testosterone compared with the younger group after PSD. Upon SR after 3 days of PSD, the testosterone level continued to rise for 5 days after sleep recovery in the younger group （P=0.013）, whereas testosterone concentrations failed to recover until day 5 in the elder group. PSD caused a more detrimental effect on serum testosterone in the elder group compared to the younger group with respect to decreases in luteinizing hormone （LH） levels. The replenishment of serum testosterone level was prohibited in the elder group suggesting that the effects of SD/SR may be age-dependent. The mechanism by which SD affects serum testosterone and how age may modify the process are still unclear.

Progressive paradoxical sleep deprivation impairs partial memory following learning tasks in rats

BACKGROUND： Complex learning tasks result in a greater number of paradoxical sleep phases, which can improve memory. The effect of paradoxical sleep deprivation, induced by ＂flower pot＂ technique, on spatial reference memory and working memory require further research. OBJECTIVE： To observe the effect of progressive paradoxical sleep deprivation in rats, subsequent to learning, on memory using the Morris Water Maze. DESIGN, TIME AND SETTING： Controlled observation experiment. The experiment was performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from December 2006 to October 2007. MATERIALS： Twenty-eight, male, Wistar rats, 3-4 months old, were provided by the Experimental Animal Center of Lanzhou University. The Morris Water Maze and behavioral analyses system was purchased from Genheart Company, Beijing, China. METHODS： All animals, according to a random digits table, were randomly divided into paradoxical sleep deprivation, tank control, and home cage control groups. Paradoxical sleep deprivation was induced by the ＂flower pot＂ technique for 72 hours, housing the rats on small platforms over water. Rats in the ＂tank control＂ and ＂home cage control＂ groups were housed either in a tank with large platforms over the water or in normal cages without paradoxical sleep deprivation. MAIN OUTCOME MEASURES： Morris Water Maze was employed for task learning and spatial memory testing. Rats in all groups were placed at six random starting points each day for four consecutive days. Each placement was repeated for two trials; the first trial represented reference memory and the second working memory. Rats in the first trial were allowed to locate the submerged platform within 120 seconds. Data, including swimming distance, escape latency, swimming velocity, percentage of time in correct quarter, and memory scores were recorded and analyzed automatically by behavioral analyses systems for Morris Water Maze. RESULTS： Twenty-eight rats were included in the final analysis, without any loss. In the first trial, between day 2 and 4, escape latency and swimming distance increased significantly in the paradoxical sleep deprivation group compared to the home cage control and tank control groups （P 〈 0.01）; percentage of time in correct quarter and memory scores, however, decreased in the paradoxical sleep deprivation group compared to the home cage control and tank control groups （P 〈 0.01）. The escape latency, swimming distance, percentage of time in correct quarter, and memory scores in the second trial was not significantly different among the three groups （P 〉 0.05）. CONCLUSION： Paradoxical sleep deprivation inhibits spatial reference memory, but not working memory.

G-protein coupled receptors and synaptic plasticity in sleep deprivation

Insufficient sleep has been correlated to many physiological and psychoneurological disorders.Over the years,our understanding of the state of sleep has transcended from an inactive period of rest to a more active state involving important cellular and molecular processes.In addition,during sleep,electrophysiological changes also occur in pathways in specific regions of the mammalian central nervous system(CNS).Activity mediated synaptic plasticity in the CNS can lead to long-term and sometimes permanent strengthening and/or weakening synaptic strength affecting neuronal network behaviour.Memory consolidation and learning that take place during sleep cycles,can be affected by changes in synaptic plasticity during sleep disturbances.G-protein coupled receptors(GPCRs),with their versatile structural and functional attributes,can regulate synaptic plasticity in CNS and hence,may be potentially affected in sleep deprived conditions.In this review,we aim to discuss important functional changes that can take place in the CNS during sleep and sleep deprivation and how changes in GPCRs can lead to potential problems with therapeutics with pharmacological interventions.

Effects of sleep deprivation on cognitive functions

Sleep deprivation （SD） is a common condition that afflicts many people in modem life. Deficits in daytime perfor- mance due to SD are experienced universally. Recent evidence indicates that SD causes impairments in cognitive functions. However, the mechanisms that SD impairs cognitive functions are not clear. This review will focus on the behavioral and neural effects of SD with the aim to elucidate the possible mechanisms of SD-induced deterioration in cognitive functions and to identify directions for future research.

Behavioral study of sleep deprivation model in caffeine and light induced zebrafish

Objective:To compare the differences in behavior of sleep deprivation models in caffeine and light induced zebrafish.Methods:A total of 72 zebrafish larvae,were selected 5 d after fertilization and randomly divided into blank control group,caffeine and light group,with 24 larvae in each group.The blank control group was given normal breeding for 24 h,while on the basis of treatment in the blank control group,the caffeine group was exposed to 200μmol/L caffeine in water and the light group to 200 lux light conditions continuously for 24 h.Results:The pigmentation of zebrafish head in the light group and the caffeine group was slightly shallow with edema of yolk sac.The activity time of the light group and the caffeine group increased compared with the blank control group(P<0.01,P<0.05),but there was no significiant difference in activity time between the light group and the caffeine group(P>0.05),The small movement time of the light group was significantly more than the caffeine group(P<0.01),while the medium movement time of the caffeine group was more than light group(P<0.05).Conclusion:Both light and caffeine can induce zebrafish sleep deprivation model effectively,and have effects on zebrafish phenotype to a certain degree,but there are differences in motor form between the two kinds of sleep-deprivation models.

The Role of Sleep Deprivation in Arrhythmias

Sleep is essential to the normal psychological and physiological activities of the human body.Increasing evidence indicates that sleep deprivation is associated with the occurrence,development,and poor treatment effects of various arrhythmias.Sleep deprivation affects not only the peripheral nervous system but also the central nervous system,which regulates the occurrence of arrhythmias.In addition,sleep deprivation is associated with apoptotic pathways,mitochondrial energy metabolism disorders,and immune system dysfunction.Although studies increasingly suggest that pathological sleep patterns are associated with various atrial and ventricular arrhythmias,further research is needed to identify specific mechanisms and recommend therapeutic interventions.This review summarizes the findings of sleep deprivation in animal experiments and clinical studies,current challenges,and future research directions in the field of arrhythmias.

Effect of chronic sleep deprivation on peak bone mass in rats: An experimental study

Objective:To investigate the effects of chronic sleep deprivation(CSD)on bone microstructure and peak bone mass(PBM)in SD rats.Methods:Twenty-four SD rats were randomly divided into CSD group and control group.In the CSD group,a CSD model was established using a new sleep deprivation instrument for rats and mice,and intervened for 5 weeks.Bone turnover markers including P1NP and CTX-1 before and after the experiment were observed.After the experiment,the left femur were scanned by Micro-CT,and the cortical bone and bone trabecula were three-dimensionally reconstructed,respectively.The bone mineral density(BMD)and relevant parameters were detected.Results:CT images of the femur(proximal ends)showed significant trabecular loss in CSD rats.Trabecular parameters including bone volume fraction(BV/TV),trabecular number(Tb.N)and trabecular separation(Tb.Sp)in the CSD group were all lower than those in the control group.The bone cortex of the middle segment of the femur and tibia in CSD rats was also lower than that in the control group.The parameters of bone cortex including total tissue area(Tt.Ar),cortical bone area(Ct.Ar)and cortical bone thickness(Ct.Th)in the CSD group were significantly lower than those in the control group(P<0.01).After chronic CSD,BMD of both bone trabecula and bone cortex of the femur was lower,while the corresponding P1NP and CTX-1 were significantly higher than those in the control group.Conclusion:Sleep plays an important role in PBM formation.CSD accelerates bone turnover and thus significantly reducing PBM in SD rats.

Sleep deprivation and associated factors among students of the Institute of Health in Jimma University, Southwest Ethiopia

Objective:Despite getting sufficient sleep being one of the most important things that we can do to keep our body and mind healthy,sleep deprivation has become a major public health concern.This study aimed to determine the prevalence of sleep deprivation and its associated factors among students of the Institute of Health in Jimma University.Methods:An institution-based cross-sectional study was conducted from April 10 to April 24 in 2019.Data were collected from 365 randomly selected participants and analyzed using Statistical Package for the Social Sciences(SPSS;version 23).Multivariate logistic regression analysis was used to identify the factors associated with sleep deprivation.The level of significance was declared at a P-value of<0.05.Results:A total of 365 participants participated,with a response rate of 97.6%.The study findings showed that 60.8%of students had sleep deprivation and 68.2%had sleep latency.Health problems(adjusted odds ratio[AOR]=1.91[95%confidence interval{CI}=1.01–3.58]),alcohol consumption[AOR=0.42(95%CI=0.2–0.89)],cigarette smoking[AOR=0.31(95%CI=0.09–0.93)],khat chewing[AOR=0.47(95%CI=0.12–0.82)],use of an electronic device before bedtime[AOR=5.26(95%CI=1.78–15.52)],and cumulative grade point average(CGPA)[AOR=0.48(95%CI=0.27–0.83)]were significantly associated with sleep deprivation.Conclusions:Sleep deprivation was common in the study area.This is mainly due to health problems,substance utilization,long-time use of an electronic device,and low CGPA.Therefore,a strategy and system should be established to limit substance use,enhance proper use of electronic devices,and create awareness on the impact of nonoptimal sleep.

Correlation between interaction anxiousness and sleep deprivation among undergraduate students

Sleep deprivation is a common problem among university students,it causes lowered cognitive skills,higher tend of suicide,risk-taking behavior and interaction anxiety.By using the Pittsburgh sleep quality index(PSQI)and Interaction Anxiousness Scale(IAS),the survey on the sleep quality and interaction anxiousness was carried out among 124 undergraduate students,in order to found the correlation between sleep deprivation and interaction anxiousness.The results showed a strong positive correlation between them.This study also investigates the difference of PSQI and IAS among students with varied disciplines and grades,and findings illustrated a poor sleep quality as well as poor interpersonal communication situation among university students.

Effect of Sleep Deprivation on Eye Movement Behavior in Flight Simulation

To examine the effect of sleep deprivation （SD） on eye movement be- havior in flight task, four subjects who were skilled in flight simulator participated in the experiment, which were asked to perform a level flight task in a flight simulator. Eye movement data and flight performance data were measured at the following hours： 11：00, 15：00, 04：00, 11：00, 15：00. The subjects workload and fatigue were assessed with the method of national aeronautics and space administration-task load index （NASA-TLX） and rating of perceived exertion （RPE）. Eye movement indices of average pupil area, av- erage saceade amplitude and average saccade velocity decreased during the 32 h of SD and they all showed significantly change in the final SD while the index of average fixa- tion time increased in the final SD. Flight performance deteriorated during the 32 h of SD, but not significantly. The feeling of fatigue and workload reported by subjects both increased during the 32 h of SD. Daily rhythm effects on the measured indices were also found, there were a obviously change at the hour of 04：00. 32 h of SD has obvious effect on eye movement behaviors which have close relation to fatigue because of SD. The eye movement measurement can be served as a tool to continually monitor fatigue online.

EFFECTS OF SLEEP DEPRIVATION ON WHOLE NIGHT POLYSOMNOGRAPHY IN HEALTHY YOUNG MEN

Objective To assess the effects of sleep deprivation (SD) on the whole night polysomnography (PSG) in healthy young men. Methods The whole night PSG was recorded by using Neurofax-1518K (Nihon Kohden, Japan) system before and after 38 h of SD among 15 healthy male subjects. Results Compared with PSG before SD, post-SD PSG showed significantly shortened sleep latency (before SD: 19.7±9.3, after SD: 5.6±7.3, P<0.05), decreased stage 1 (S1) non-rapid eye movement (NREM) sleep [before SD: (9.2±1.9)%, after SD: (4.0±1.4)%, P<0.05], and increased stage 4 (S4) NREM sleep [before SD: (10.3±3.7)%, after SD: (26.2±4.3)%, P<0.01]. Conclusion During post-SD sleep, the proportion of S4 NREM sleep was increased as compensation in healthy male. In addition, SD was proved to affect electrophysiological brain activities in normal people.

Chronic sleep deprivation induces alterations in DNA and RNA modifications by liquid chromatography-mass spectrometry analysis

Sleep deprivation(SD)is a widespread issue that disrupts the lives of millions of people.These effects ini-tiate as changes within neurons,specifically at the DNA and RNA level,leading to disruptions in neuronal plasticity and the dysregulation of various cognitive functions,such as learning and memory.Nucleic acid epigenetic modifications that could regulate gene expression have been reported to play crucial roles in this process.However,there is a lack of comprehensive research on the correlation of SD with nucleic acid epigenetic modifications.In the current study,we aimed to systematically investigate the landscape of modifications in DNA as well as in small RNA molecules across multiple tissues,including the heart,liver,kidney,lung,hippocampus,and spleen,in response to chronic sleep deprivation(CSD).Using liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis,we characterized the dynamic changes in DNA and RNA modification profiles in different tissues of mice under CSD stress.Specifically,we ob-served a significant decrease in the level of 5-methylcytosine(5mC)and a significant increase in the level of 5-hydroxymethylcytosine(5hmC)in the kidney in CSD group.Regarding RNA modifications,we observed an overall increased trend for most of these significantly changed modifications across six tis-sues in CSD group.Our study sheds light on the significance of DNA and RNA modifications as crucial epigenetic markers in the context of CSD-induced stress.

Sleep Deprivation Selectively Down-Regulates Astrocytic 5-HT2B Receptors and Triggers Depressive-Like Behaviors via Stimulating P2X7 Receptors in Mice

Chronic loss of sleep damages health and disturbs the quality of life.Long-lasting sleep deprivation(SD)as well as sleep abnormalities are substantial risk factors for major depressive disorder,although the underlying mechanisms are not clear.Here,we showed that chronic SD in mice promotes a gradual elevation of extracellular ATP,which activates astroglial P2X7 receptors(P2X7Rs).Activated P2X7Rs,in turn,selectively down-regulated the expression of 5-HT2B receptors(5-HT2BRs)in astrocytes.Stimulation of P2X7Rs induced by SD selectively suppressed the phosphorylation of AKT and FoxO3 a in astrocytes,but not in neurons.The overexpression of FoxO3a in astrocytes inhibited the expression of 5-HT2BRs.Down-regulation of 5-HT2BsRs instigated by SD suppressed the activation of STAT3 and relieved the inhibition of Ca2+-dependent phospholipase A2.This latter cascade promoted the release of arachidonic acid and prostaglandin E2.The depression-like behaviors induced by SD were alleviated in P2X7R-KO mice.Our study reveals the mechanism underlying chronic SD-induced depression-like behaviors and suggests 5-HT2BRs as a key target for exploring therapeutic strategies aimed at the depression evoked by sleep disorders.