Electroacupuncture inhibits hippocampal oxidative stress and autophagy in sleep-deprived rats through the protein kinase B and mechanistic target of rapamycin signaling pathway.

OBJECTIVE: To investigate the effects of acupuncture on learning and memory impairment, oxidative stress and autophagy induced by sleep depriv ation in rats, and to analyze the related mechanism. METHODS: Thirty Wistar rats were randomly divided into a normal group, sleep deprivation group and acupuncture group. The rat model of sleep deprivation was established by a modified multiplatform sleep deprivation method. The Baihui (GV20), Shenmen (HT7) and Sanyinjiao (SP6) acupoints of rats were located to give electroacupuncture (density wave, frequency 20 Hz, intensity 1 mA) to maintain the needle feeling, and to keep the needle for 15 min and continuous acupuncture for 7 d. The spatial learning and memory abilities of the rats were detected by the water maze test. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the brain were detected by an assay kit, and the autophagy related proteins light chain 3 alpha (LC3A), light chain 3 beta (LC3B) and Beclin 1 and the activation of the protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) signaling pathway in the rat's brain were detected by Western blotting. RESULTS: Compared with the normal group, the time spent in the target quadrant (P < 0.05) and the number of times entering the target quadrant (P < 0.05) in the rats of sleep deprivation group were significantly reduced, and the content of MDA was significantly increased (P < 0.01), while the activities of SOD and GPX (P < 0.01) in the brain were significantly decreased, and LC3A Ⅱ/Ⅰ, LC3B Ⅱ/Ⅰ and Beclin 1 increased significantly (P < 0.01), while p-AKT (ser473)/AKT, p-mTOR (ser2448)/mTOR and p-p70s6K (thr389)/p70S6 decreased significantly (P < 0.01). Compared with the sleep deprivation group, the time spent in the target quadrant and the times of entering the target quadrant (P < 0.05) in the rats of acupuncture group after 7 d of treatment were significantly increased, Additionally, the content of MDA was significantly decreased (P < 0.05), while the activities of SOD and GPX (P < 0.05) in the brain were significantly increased. Moreover, the levels of LC3A Ⅱ/Ⅰ, LC3BⅡ/Ⅰ and Beclin 1 decreased significantly (P < 0.05), and that of p-AKT (ser473)/AKT, p-mTOR (ser2448)/mTOR and p-p70s6K (thr389)/p70s6k increased significantly (P < 0.05). CONCLUSION: Acupuncture can significantly improve the learning and memory damage caused by sleep deprivation and inhibit oxidative stress and autophagy, and its effect is related to the activation of AKT/mTOR signaling.

Maternal sleep deprivation disrupts glutamate metabolism in offspring rats.

Maternal sleep deprivation (MSD) has emerged as a significant public health concern, yet its effects on offspring metabolism remain poorly understood. This study investigated the metabolomic implications of MSD on offspring cognitive development, with a particular focus on alterations in glutamate metabolism. Pregnant rats were subjected to sleep deprivation during late gestation. Plasma and brain samples from their offspring were collected at different postnatal days (P1, P7, P14, and P56) and analyzed using untargeted metabolomics with liquid chromatography-mass spectrometry. Metabolomic analysis revealed significant differences in various amino acids, including L-glutamate, L-phenylalanine, L-tyrosine, and L-tryptophan, which are crucial for cognitive function. Subsequent differential analysis and partial least squares discriminant analysis (sPLS-DA) demonstrated a gradual reduction in these metabolic differences in the brain as the offspring underwent growth and development. KEGG pathway analysis revealed differential regulation of several pathways, including alanine, aspartate, and glutamate metabolism, glutathione metabolism, arginine biosynthesis, aminoacyl-tRNA biosynthesis, histidine metabolism, and taurine and hypotaurine metabolism, at different developmental stages. Mantel and Spearman analyses indicated that the observed changes in metabolites in MSD progeny may be related to various gut microbes, Ruminococcus_1, Ruminococcaceae_UCG-005, and Eubacterium_coprostanoligenes_group. Biochemical assays further demonstrated developmental changes in the L-glutamate metabolic pathway. Collectively, these findings suggest that MSD not only affects maternal well-being but also has enduring metabolic consequences for offspring, particularly impacting pathways linked to cognitive function. This highlights the importance of addressing maternal sleep health to mitigate potential long-term consequences for offspring.

Extracellular vesicles and sleep deprivation.

Sleep is vital in preserving mental and physical well-being by aiding bodily recovery, strengthening the immune system, and regulating hormones. It enhances memory, concentration, and mood regulation, reducing stress and anxiety. Sleep deprivation, a common phenomenon affecting approximately 20% of adults, decreases performance, alertness, and health integrity. Furthermore, it triggers physiological changes, including increased stress hormone levels, leading to various disorders such as hyperglycemia and hypertension. Recent research explores the role of extracellular vesicles (EVs) in sleep-related conditions. EVs, released by cells, play vital roles in intercellular communication and biomarker potential. Studies indicate that sleep deprivation influences EV release, impacting cancer progression, endothelial inflammation, and thrombosis risk. Understanding these mechanisms offers insights into therapeutic interventions. Thus, multidisciplinary approaches are crucial to unraveling the complex interactions between sleep, EVs, and health, providing direction for effective prevention and treatment approaches for sleep disorders and related conditions.

Exploring the protective role of green tea extract against cardiovascular alterations induced by chronic REM sleep deprivation via modulation of inflammation and oxidative stress.

BACKGROUND: Chronic Rapid eye movement (REM) sleep deprivation has been associated with various cardiovascular alterations, including disruptions in antioxidant defense mechanisms, lipid metabolism, and inflammatory responses. This study investigates the therapeutic potential of green tea extract (GTE) in mitigating these adverse effects. METHODS: A total of 24 male Wistar albino rats were used in this study and divided into the control group (n = 8), Chronic-REM Sleep Deprivation (CRSD) Group (n = 8) and Chronic-REM SD + Green Tea 200 (CRSD + GTE200) Group (n = 8). After 21 days, a comprehensive analysis of paraoxonase (PON1), arylesterase (ARE), malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), proinflammatory cytokines, and lipid profiles in aortic tissue, heart tissue, and serum was conducted in a sleep-deprived rat model. RESULTS: Chronic REM sleep deprivation led to a significant reduction in PON1 and ARE levels in aortic (p = 0.046, p = 0.035 respectively) and heart tissues (p = 0.020, p = 0.019 respectively), indicative of compromised antioxidant defenses. MDA levels increased, and NOx levels decreased, suggesting oxidative stress and impaired vascular function. Lipid profile alterations, including increased triglycerides and total cholesterol, were observed in serum. Elevated levels of inflammatory cytokines (IL-6 and TNF-alpha) further indicated an inflammatory response (p = 0.007, p = 0.018 respectively). GTE administration demonstrated a protective role, restoring antioxidant enzyme levels, suppressing lipid peroxidation, and improving NOx levels. CONCLUSION: These findings suggest the therapeutic potential of GTE in alleviating the cardiovascular impairments of chronic REM sleep deprivation, emphasizing its candidacy for further clinical exploration as a natural intervention in sleep-related disorders and associated cardiovascular risks.

Phloretin alleviates sleep deprivation-induced cognitive impairment by reducing inflammation through PPARγ/NF-κB signaling pathway.

Sleep loss leads to significant pathophysiological consequences, including cognitive impairment. The neuroinflammation are pivotal factors in the pathogenesis of cognitive impairment induced by sleep loss. The phloretin (PHL), derived from peel of juicy fruits, has demonstrated potent anti-inflammatory properties. However, the precise influence of PHL on the cognitive impairment triggered by sleep loss and its underlying mechanism remain uncertain. In the present study, mice were subjected to sleep deprivation (SD) paradigm. Cognitive impairment induced by SD were significantly relieved by administration of PHL in a dose-dependent manner. Furthermore, PHL not only mitigated the synaptic losses but also enhanced dendritic spine density and neuronal activity within mice hippocampus following exposure to SD. Moreover, PHL treatment decreased the microglial numbers and altered microglial morphology in the hippocampus to restore the M1/M2 balances; these effects were accompanied by regulation of pro-/anti-inflammatory cytokine production and secretion in SD-exposed mice. Additionally, in vivo and in vitro studies showed PHL might attenuate the inflammation through the PPARγ/NF-κB pathway. Our findings suggest that PHL exerts inhibitory effects on microglia-mediated neuroinflammation, thereby providing protection against cognitive impairment induced by SD through a PPAR-γ dependent mechanism. The results indicate PHL is expected to provide a valuable candidate for new drug development for SD-induced cognitive impairment in the future.

Safflower Improves Memory, Learning, and Behavior in Rats Subjected to Sleep Deprivation.

BACKGROUND: Sleep is a physiological process that provides the body with a window for recovery and restoration. Intriguingly, even short-term sleep deprivation can impair brain memory, emotional capacity, information processing, and attention. Safflower (Carthamus tinctorius L.) has been shown to attenuate memory loss and improve anxiety and depression. OBJECTIVE: This study aims to study the possible therapeutic effect of safflower on sleep deprivation-dependent effects on memory and behavior. MATERIALS AND METHODS: Thirty young male Wistar albino rats were acclimatized, trained, and then assigned to three random groups: control (C), sleep-deprived (SD), and sleep-deprived Safflower-treated (SD+Sf) groups. Morris Water Maze (MWM) and Elevated Plus Maze (EPM) tests were used to study spatial memory and learning and anxiety-related behavior, respectively, in the study groups. RESULTS: There was a significant deterioration in learning and memory, as tested by the MWM in the SD group, compared to the C group. This included prolonged test duration, reduced average speed, and longer travel distance. Treatment with safflower significantly improved MWM test performance in the SD+Sf group when compared to the SD group. When compared to the C group, rats in the SD group demonstrated altered EPM test parameters suggestive of anxiety-like behavior. These included spending more time in the closed arms, spending less time in the open arms, and having fewer entries in the open arms. Rats in the SD+Sf group showed improved EPM test parameters when compared to the SD group. CONCLUSION: Safflower significantly ameliorated sleep deprivation induced by memory loss and altered behavior. Safflower supplementation may provide potential memory-enhancing and preserving, anxiolytic, and antidepressant therapeutic roles.

[Effects of Schisandrae Chinensis Fructus Lignans on Alertness of Rats With Sleep Deprived by Treadmill Exercise].

Objective To investigate the effects of Schisandrae Chinensis Fructus lignans on the alertness of the rats with sleep deprived by treadmill exercise and the underlying neurobiological mechanism. Methods According to the random number table method,SD male rats were assigned into control,sleep deprivation,low-,medium-,and high-dose Schisandrae Chinensis Fructus lignans,and atomoxetine hydrochloride groups,with 8 rats in each group.The rats in other groups except the control group were subjected to sleep deprivation by treadmill exercise for 3 d.During the deprivation period,each administration group was administrated with the corresponding drug by gavage,and a 5-9 hole tester was used to test the alertness performance of rats in each group. Furthermore,other SD male rats were selected and randomized into control,sleep deprivation,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride groups,with 10 rats in each group.The rats were modeled with the sleep deprivation method the same as that above and administrated with corresponding agents.ELISA was employed to measure the serum level of orexin A in each group of rats.The protein levels of c-Fos,orexin receptor 1,and orexin receptor 2 in the prefrontal cortex of rats in each group were observed by immunofluorescence and Western blotting. Results Compared with the control group,sleep deprivation reduced the choice accuracy (P<0.001) and increased the omission responses,omission percent,and mean correct response latency (P=0.002,P=0.003,P=0.020).Compared with the sleep deprivation group,medium- and high-dose Schisandrae Chinensis Fructus lignans and atomoxetine hydrochloride improved the alertness of rats,as demonstrated by the increased choice accuracy (P=0.001,P=0.006,P<0.001) and reduced omission responses (P=0.001,P=0.001,P<0.001),omission percent (P=0.001,P=0.002,P<0.001),and mean correct response latency (P=0.018,P=0.003,P=0.014).Compared with the control group,the sleep deprivation group showed elevated level of orexin A in the serum (P<0.001),up-regulated expression of c-Fos (P<0.001),and down-regulated expression of orexin receptor 1 (P=0.037) in the prefrontal cortex.Compared with the sleep deprivation group,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride lowered the orexin A level in the serum (P=0.005,P=0.029),down-regulated the expression of c-Fos (P=0.028,P=0.036),and up-regulated the expression of orexin receptor 1 (P=0.043,P=0.013) in the prefrontal cortex. Conclusion Schisandrae Chinensis Fructus lignans may antagonize the alertness decrease caused by sleep deprivation by regulating the secretion of orexin and the expression of orexin receptor 1 in the prefrontal cortex.

Sleep Debt and Insulin Resistance: What's Worse, Sleep Deprivation or Sleep Restriction?

Objective To evaluate which condition of sleep debt has a greater negative impact on insulin resistance: sleep deprivation for 24 hours or 4 hours of sleep restriction for 4 nights. Materials and Methods In total, 28 healthy male subjects aged 18 to 40 years were recruited and randomly allocated to two groups: sleep deprivation (SD) and sleep restriction (SR). Each group underwent two conditions: regular sleep (11 pm to 7 am ) and total sleep deprivation for 24 hours (SD); regular sleep (11 pm to 7 am ) and 4 nights of sleep restriction (SR) (1 am to 5 am ). The oral glucose tolerance test (OGTT) was performed, and baseline glucose, insulin, free fatty acids (FFAs), and cortisol were measured. In addition, the area under the curve (AUC) for glucose and insulin, the homeostasis model assessment of insulin resistance (HOMA-IR), and the Matsuda Index (Insulin Sensitivity Index, ISI) were calculated. Results Glucose and insulin had a similar pattern between groups, except at the baseline, when insulin was higher in the sleep debt condition of the SR when compared with the SD ( p < 0.01). In the comparison between regular sleep and sleep debt, the SD had a higher insulin AUC ( p < 0.01) and FFAs ( p = 0.03) after sleep deprivation, and insulin and the insulin AUC increased ( p < 0.01 for both), while the ISI decreased ( p = 0.02) after sleep restriction in the SR. In baseline parameters covariate by the condition of regular sleep, insulin ( p = 0.02) and the HOMA-IR ( p < 0.01) were higher, and cortisol ( p = 0.04) was lower after sleep restriction when compared with sleep deprivation. Conclusion Sleep restriction for 4 consecutive nights is more detrimental to energy metabolism because of the higher insulin values and insulin resistance compared with an acute period of sleep deprivation of 24 hours.

Stress and Sleep Deprivation Experienced by Bus Drivers of Government Bus Depots in an Urban Area of Chengalpattu District in South India.

Background Driving a bus is far more stressful than other professions. Bus drivers also take more sick leave than other workers because of the physical and mental demands of their employment. Bus drivers are especially vulnerable because of their intense work environment, poor sleep, and poor food pattern. The aim of the study was to assess stress and sleep deprivation of the government bus drivers in Chengalpattu District in Tamil Nadu and to identify the sociodemographic factors influencing them. Methodology An analytical cross-sectional study was conducted among 429 government bus drivers working under Tamil Nadu State Transport Corporation (TNSTC )in selected government bus depots in the urban area of Chengalpattu District in Tamil Nadu, India. The principal investigator collected the data by using a semi-structured questionnaire which comprises six parts, i.e., sociodemographic variables, job-related factors, comorbidity, habits, stress assessed by using the Perceived Stress Scale (PSS-10), and sleep deprivation assessed by using the Epworth Sleepiness Scale (ESS). Results In the present study, the mean age of participants was 47.683 years. Hindus comprise 95.3% of the sample, and 96.7% are married. Approximately 47.6% of the drivers have achieved a higher secondary education. The average time spent working as a heavy vehicle driver was 20.4 years. About 37.1% (159 individuals) have hypertension, making it the most prevalent comorbidity. In this study, 47.3% (203 participants) reported very poor sleep, 35.7% (153 participants) reported average sleep, and 17.0% (73 participants) reported good sleep. Inferential statistics revealed that those drivers who were degree holders took less than three breaks in duty time, slept over six hours at night, had the habit of smoking and drinking alcohol, and took more than 60 minutes to fall asleep experienced very poor sleep according to the ESS. In this study, 57.1% (245 participants) reported moderate stress levels, 24.2% (104 participants) showed high levels of perceived stress, and 18.6% (80 participants) reported low stress levels. Inferential statistics revealed that those drivers who were Muslims, degree holders, those with primary education, smokers, alcohol consumers, drivers with very poor sleep, and those who took more than six days of casual leave in the past six months experienced high stress according to the PSS-10. Conclusion Implementing effective health management strategies and minimizing work-related stress will lead to a decrease in work-related disorders among drivers. TNSTC should ensure enough lodging facilities for drivers at depots, bus terminals, and outstations. They require a minimum of eight hours of sleep every day to maintain optimal physical well-being.

Modifications in the Composition of the Gut Microbiota in Rats Induced by Chronic Sleep Deprivation: Potential Relation to Mental Disorders.

Introduction: Sleep deprivation(SD) has numerous negative effects on mental health. A growing body of research has confirmed the implication of gut microbiota in mental disorders. However, the specific modifications in mammalian gut microbiota following SD exhibit variations across different studies. Methods: Male specific-pathogen-free Wistar rats were given a modified multiple-platform exposure for 7 days of SD. Fecal samples were obtained from the control and SD groups both at baseline and after 7 days of SD. We utilized 16S rDNA gene sequencing to investigate the gut microbial composition and functional pathways in rats. Results: Analysis of the microbiota composition revealed a significant change in gut microbial composition after chronic SD, especially at the phylum level. The relative abundances of p_Firmicutes, g_Romboutsia, and g_Enterococcus increased, whereas those of p_Bacteroidetes, p_Verrucomicrobia, p_Fusobacteria, g_Akkermansia, and g_Cetobacterium decreased in animals after chronic SD compared with controls or animals before SD. The ratio of Firmicutes to Bacteroidetes exhibited an increase following SD. The relative abundance of gut microbiota related to the functional pathways of GABAergic and glutamatergic synapses was observed to be diminished in rats following SD compared to pre-SD. Conclusion: Collectively, these findings suggest that chronic SD causes significant alterations in both the structural composition and functional pathways of the gut microbiome. Further researches are necessary to investigate the chronological and causal connections among SD, the gut microbiota and mental disorders.

Sleep Deprivation Triggers the Excessive Activation of Ovarian Primordial Follicles via ß2 Adrenergic Receptor Signaling.

Sleep deprivation (SD) is observed to adversely affect the reproductive health of women. However, its precise physiological mechanisms remain largely elusive. In this study, using a mouse model of SD, it is demonstrated that SD induces the depletion of ovarian primordial follicles, a phenomenon not attributed to immune-mediated attacks or sympathetic nervous system activation. Rather, the excessive secretion of stress hormones, namely norepinephrine (NE) and epinephrine (E), by overactive adrenal glands, has emerged as a key mediator. The communication pathway mediated by the KIT ligand (KITL)-KIT between granulosa cells and oocytes plays a pivotal role in primordial follicle activation. SD heightened the levels of NE/E that stimulates the activation of the KITL-KIT/PI3K and mTOR signaling cascade in an ß2 adrenergic receptor (ADRB2)-dependent manner, thereby promoting primordial follicle activation and consequent primordial follicle loss in vivo. In vitro experiments further corroborate these observations, revealing that ADRB2 upregulates KITL expression in granulosa cells via the activation of the downstream cAMP/PKA pathway. Together, these results reveal the significant involvement of ADRB2 signaling in the depletion of ovarian primordial follicles under sleep-deprived conditions. Additionally, ADRB2 antagonists are proposed for the treatment or prevention of excessive activation of primordial follicles induced by SD.

Brain structural changes underlying clinical symptom improvement following fast-acting treatments in treatment resistant depression.

BACKGROUND: Electroconvulsive therapy (ECT), ketamine infusion (KI), and total sleep deprivation (TSD) are effective and fast in treating patients with treatment-resistant depression (TRD). However, it remains unclear whether the three treatments have the same effect on clinical symptom improvement and have common brain structural mechanisms. METHODS: The current study included 127 TRD patients and 37 healthy controls, which were obtained from the Perturbation of the Treatment Resistant Depression Connectome Project. We aimed to investigate the shared and distinct brain structural changes underlying clinical symptom improvement among ECT, KI, and TSD treatments. RESULTS: All of the three treatments significantly reduced the depressive symptoms in TRD patients, but they differently affected other clinical measurements. Neuroimaging results also revealed that all of ECT, KI, and TSD treatments significantly increased gray matter volume of left caudate after treatment in TRD patients. However, the gray matter volume of other brain regions including hippocampus, parahippocampus, amygdala, insula, fusiform gyrus, several occipital and temporal areas was increased only after ECT treatment. Still, the baseline or the change of gray matter volume did not correlate with the depressive symptom improvement for all of the three treatments. LIMITATIONS: A higher sample size would be required to further validate our findings. CONCLUSIONS: The results observed in the current study suggested that the ECT, KI, and TSD treatments differently affected clinical measurements and brain structures in TRD patients, though all of them were effective in depressive symptom improvement, which might facilitate the development of personalized treatment protocol for this disease.

Are Adolescent Athletes Sleeping Enough? An Observational Study of Sleep Parameters during Schooldays and Holidays.

Background: Inconsistent sleep schedules, frequent awakening after sleep onset (WASO), and decreased sleep efficiency (SE) are common issues among adolescent team sports athletes. Moreover, research indicates that sleep problems are enhanced across schooldays. The aim of the present study was to assess sleep patterns of adolescent athletes and compare sleep parameters between schooldays and holidays. Methods: The chronotype and sleep quality of twelve adolescent basketball players (mean age: 15.58 ± 0.67 years) were assessed. Objective sleep parameters were then analyzed using actigraphy over a 12-day period, which included six days during the school period and six days during holidays. Results: Data showed that total sleep time (TST), SE, and WASO (382.48 min, 81.81%, and 66.70 min, respectively) did not meet international recommendations for sleep quantity and quality. During school weekdays, time in bed (TIB), TST, and SE significantly decreased compared to weekends (p < 0.001, d = -1.49; p < 0.001, d = -1.64; and p = 0.01, d = -0.89, respectively). On weekdays, TIB, TST, and WASO were significantly lower on schooldays compared to holidays (p < 0.001, d = -1.83; p < 0.01, d = -1.01; and p = 0.02, d = -0.77, respectively). While no significant difference was observed in social jetlag, the mid-point of sleep was significantly later on holiday weekdays compared to school weekdays (p < 0.05, d = 0.65). Conclusions: Adolescent athletes experience insufficient sleep, especially on school weekdays, which is partially improved during weekends and holidays. Although sleep duration was longer during holidays, our results suggest that adolescent athletes' sleep was more fragmented. Consequently, it remains crucial to implement strategies to enhance their sleep health (e.g., napping).

Locus coeruleus microstructural integrity is associated with vigilance vulnerability to sleep deprivation.

Insufficient sleep compromises cognitive performance, diminishes vigilance, and disrupts daily functioning in hundreds of millions of people worldwide. Despite extensive research revealing significant variability in vigilance vulnerability to sleep deprivation, the underlying mechanisms of these individual differences remain elusive. Locus coeruleus (LC) plays a crucial role in the regulation of sleep-wake cycles and has emerged as a potential marker for vigilance vulnerability to sleep deprivation. In this study, we investigate whether LC microstructural integrity, assessed by fractional anisotropy (FA) through diffusion tensor imaging (DTI) at baseline before sleep deprivation, can predict impaired psychomotor vigilance test (PVT) performance during sleep deprivation in a cohort of 60 healthy individuals subjected to a rigorously controlled in-laboratory sleep study. The findings indicate that individuals with high LC FA experience less vigilance impairment from sleep deprivation compared with those with low LC FA. LC FA accounts for 10.8% of the variance in sleep-deprived PVT lapses. Importantly, the relationship between LC FA and impaired PVT performance during sleep deprivation is anatomically specific, suggesting that LC microstructural integrity may serve as a biomarker for vigilance vulnerability to sleep loss.

Triphala ameliorates cognitive deficits and anxiety via activation of the Nrf2/HO-1 axis in chronic sleep-deprived mice.

Triphala is renowned for its curative attributes and has been utilized for centuries to address diverse health ailments. Moreover, the active component of Triphala, polyphenols, is widely recognized for its excellent pharmacological activities, such as anti-inflammatory properties, and has been utilized as a potential natural remedy. However, the precise mechanism through which Triphala alleviates cognitive dysfunction and anxiety induced by chronic sleep deprivation (SD) remains restricted. The objective of this investigation is to examine and clarify the potential mechanism of action that underlies the therapeutic benefits of Triphala in addressing cognitive dysfunction and anxiety induced by chronic SD. Our results demonstrated that Triphala significantly alleviates chronic SD-induced behavioral abnormalities. Additionally, Triphala was highly effective at preventing histopathological or morphological damage to neurons located in the hippocampus. The therapeutic effects of Triphala in treating cognitive dysfunction and anxiety induced by chronic SD involve the modulation of several biological pathways, including inflammation and immune responses, oxidative stress, cell growth and differentiation, metabolism, and neurotransmitter communication. Moreover, our study illustrated that Triphala increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and significantly activated the Nrf2/hemeoxygenase-1 (HO-1) axis. Additionally, the neuroprotective properties of Triphala were found to be counteracted by the Nrf2 inhibitor ML385. Our study represented the first to unveil that Triphala exerts therapeutic benefits in alleviating chronic SD-induced cognitive deficits and anxiety by activation of the Nrf2/HO-1 axis. Triphala emerges as a promising nutraceutical ingredient for mitigating cognitive deficits and anxiety linked to chronic SD.

Transcriptional dynamics of sleep deprivation and subsequent recovery sleep in the male mouse cortex.

Sleep is an essential, tightly regulated biological function. Sleep is also a homeostatic process, with the need to sleep increasing as a function of being awake. Acute sleep deprivation (SD) increases sleep need, and subsequent recovery sleep (RS) discharges it. SD is known to alter brain gene expression in rodents, but it remains unclear which changes are linked to sleep homeostasis, SD-related impairments, or non-sleep-specific effects. To investigate this question, we analyzed RNA-seq data from adult wild-type male mice subjected to 3 and 5-6 hours of SD and 2 and 6 hours of RS after SD. We hypothesized molecular changes associated with sleep homeostasis mirror sleep pressure dynamics as defined by brain electrical activity, peaking at 5-6 hours of SD, and are no longer differentially expressed after 2 hours of RS. We report 5-6 hours of SD produces the largest effect on gene expression, affecting approximately half of the cortical transcriptome, with most differentially expressed genes (DEGs) downregulated. The majority of DEGs normalize after 2 hours of RS and are involved in redox metabolism, chromatin regulation, and DNA damage/repair. Additionally, RS affects gene expression related to mitochondrial metabolism and Wnt-signaling, potentially contributing to its restorative effects. DEGs associated with cholesterol metabolism and stress response do not normalize within 6 hours and may be non-sleep-specific. Finally, DEGs involved in insulin signaling, MAPK signaling, and RNA-binding may mediate the impairing effects of SD. Overall, our results offer insight into the molecular mechanisms underlying sleep homeostasis and the broader effects of SD.

A rapid and reliable targeted LC-MS/MS method for quantitative analysis of the Tryptophan-NAD metabolic network disturbances in tissues and blood of sleep deprivation mice.

BACKGROUND: TRY-NAD metabolic network includes TRY (tryptophan), 5-HT (5-hydroxytryptamine), KYN (kynurenine), and NAD (nicotinamide adenine dinucleotide) pathway, which plays a significant role in neurological diseases and ageing. It is important to monitor these metabolites for studying the pathological anatomy of disease and treatment of responses evaluation. Although previous studies have reported quantitative methods for several metabolites in the network, the bottlenecks of simultaneously quantifying the whole metabolic network are their similar structures, diverse physico-chemical properties, and instability. Standardized protocols for the whole metabolic network are still missing, which hinders the in-depth study of TRY-NAD metabolic network in laboratory research and clinical screening. RESULTS: We developed a LC-MS/MS method for quantifying 28 metabolites in the TRY-NAD network simultaneously. Optimization was done for the mass spectral parameters, chromatographic conditions and sample pretreatment process. The developed method was fully validated in terms of standard curves, sensitivity, carryover, recovery, matrix effect, accuracy, precision, and stability. The pretreatment of 30 samples only takes 90 min, and the LC-MS/MS running time of one sample is only 13 min. With this method, we bring to light the chaos of global TRY-NAD metabolic network in sleep deprivation mice for the first time, including serum, clotted blood cells, hippocampus, cerebral cortex, and liver. NAD pathway levels in brain and blood decreased, whereas the opposite happened in the liver. The 5-HT pathway decreased and the concentration of KYN increased significantly in the brain. The concentration of many metabolites in KYN pathway (NAD+ de novo synthesis pathway) increased in the liver. SIGNIFICANCE: This method is the first time to determine the metabolites of KYN, 5-HT and NAD pathway at the same time, and it is found that TRY-NAD metabolic network will be disordered after sleep deprivation. This work clarifies the importance of the pH of the extraction solution, the time and temperature control in pretreatment in standardized protocols building, and overcoming the problems of inconsistent sample pretreatment, separation, matrix effect interference and potential metabolite degradation. This method exhibits great prospects in providing more information on metabolic disturbances caused by sleep deprivation as well as neurological diseases and ageing.

Enhanced diversity on connector hubs following sleep deprivation: Evidence from diffusion and functional magnetic resonance imaging.

Sleep deprivation has been demonstrated to exert widespread and intricate impacts on the brain network. The human brain network is a modular network composed of interconnected nodes. This network consists of provincial hubs and connector hubs, with provincial hubs having diverse connectivities within their own modules, while connector hubs distribute their connectivities across different modules. The latter is crucial for integrating information from various modules and ensuring the normal functioning of the modular brain. However, there has been a lack of systematic investigation into the impact of sleep deprivation on brain connector hubs. In this study, we utilized functional connectivity from resting-state functional magnetic resonance imaging, as well as structural connectivity from diffusion-weighted imaging, to systematically explore the variation of connector hub properties in the cerebral cortex after one night of sleep deprivation. The normalized participation coefficients (PCnorm) were utilized to identify connector hubs. In both the functional and structural networks, connector hubs exhibited a significant increase in average PCnorm, indicating the diversity enhancement of the connector hub following sleep deprivation. This enhancement is associated with increased network cost, reduced modularity, and decreased small-worldness, but enhanced global efficiency. This may potentially signify a compensatory mechanism within the brain following sleep deprivation. The significantly affected connector hubs were primarily observed in both the Control Network and Salience Network. We believe that the observed results reflect the increasing demand on the brain to invest more effort at preventing performance deterioration after sleep loss, in exchange for increased communication efficiency, especially involving systems responsible for neural resource allocation and cognitive control. These results have been replicated in an independent dataset. In conclusion, this study has enhanced our understanding of the compensatory mechanism in the brain response to sleep deprivation. This compensation is characterized by an enhancement in the connector hubs responsible for inter-modular communication, especially those related to neural resource and cognitive control. As a result, this compensation comes with a higher network cost but leads to an improvement in global communication efficiency, akin to a more random-like network manner.

Association between Enhanced Effective Connectivity from the Cuneus to the Middle Frontal Gyrus and Impaired Alertness after Total Sleep Deprivation.

BACKGROUND: Sleep deprivation (SD) can impair an individual's alertness, which is the basis of attention and the mechanism behind continuous information processing. However, research concerning the effects of total sleep deprivation (TSD) on alertness networks is inadequate. In this study, we investigate the cognitive neural mechanism of alertness processing after TSD. METHODS: Twenty-four college students volunteered to participate in the study. The resting-state electroencephalogram (EEG) data were collected under two conditions (rested wakefulness [RW], and TSD). We employed isolated effective coherence (iCoh) analysis and functional independent component analysis (fICA) to explore the effects of TSD on participants' alertness network. RESULTS: This study found the existence of two types of effective connectivity after TSD, as demonstrated by iCoh: from the left cuneus to the right middle frontal gyrus in the ß3 and γ bands, and from the left angular gyrus to the left insula in the δ, θ, α, ß1, ß3, and γ bands. Furthermore, Pearson correlation analysis showed that increased effective connectivity between all the bands had a positive correlation with increases in the response time in the psychomotor vigilance task (PVT). Finally, fICA revealed that the neural oscillations of the cuneus in the α2 bands increased, and of the angular gyrus in the α and ß1 bands decreased in TSD. CONCLUSIONS: TSD impairs the alertness function among individuals. Increased effective connectivity from the cuneus to the middle frontal gyrus may represent overloads on the alertness network, resulting in participants strengthening top-down control of the attention system. Moreover, enhanced effective connectivity from the angular gyrus to the insula may indicate a special perception strategy in which individuals focus on salient and crucial environmental information while ignoring inessential stimuli to reduce the heavy burden on the alertness network. CLINICAL TRIAL REGISTRATION: No: ChiCTR2400088448. Registered 19 August 2024, https://www.chictr.org.cn.

The diagnostic value of sleep-deprived EEG in epilepsy: A meta-analysis.

Sleep deprivation has been studied as a method to induce sleep before EEG testing to improve the diagnosis of epilepsy. However, the effectiveness of sleep deprivation in diagnosing epilepsy through EEG in humans showed conflicting findings in previous studies. This meta-analysis aimed to provide statistical evidence for the diagnostic value of sleep-deprived EEG in epilepsy. A systematic search of the Web of Science and PubMed databases identified 12 relevant studies from May 1997 to the present. These studies were included to examine the diagnostic value of sleep-deprived EEG in epilepsy and its associated clinical variables, such as patient age, duration of sleep deprivation, and EEG recording duration. The results of the random effects model did not show a significant overall diagnostic effect for sleep-deprived EEG in epilepsy, but revealed high heterogeneity among the studies. Notably, this heterogeneity was not accounted for by the clinical variables analyzed. Upon excluding outliers, a trend suggesting a modest diagnostic value of sleep-deprived EEG emerged. The high heterogeneity among studies indicates the need for a standardized protocol for sleep deprivation in future studies. Overall, while sleep deprivation may have a small positive effect on EEG-based epilepsy diagnosis, further research is needed to better understand its impact and optimize its use in clinical practice.