Sleep deprivation boosts O2·- levels in the brains of mice as visualized by a Golgi apparatus-targeted ratiometric fluorescence nanosensor.

Sleep deprivation (SD) is highly prevalent in the modern technological world. Emerging evidence shows that sleep deprivation is associated with oxidative stress. At the organelle level, the Golgi apparatus actively participates in the stress response. In this study, to determine whether SD and Golgi apparatus stress are correlated, we rationally designed and fabricated a novel Golgi apparatus-targeted ratiometric nanoprobe called Golgi dots for O2·- detection. This probe exhibits high sensitivity and selectivity in cells and brain slices of sleep-deprived mice. Golgi dots can be readily synthesized by coprecipitation of Golgi-F127, an amphiphilic polymer F127 modified with a Golgi apparatus targeting moiety, caffeic acid (CA), the responsive unit for O2·-, and red emissive carbon nanodots (CDs), which act as the reference signal. The fluorescence emission spectrum of the developed nanoprobe showed an intense peak at 674 nm, accompanied by a shoulder peak at 485 nm. As O2·- was gradually added, the fluorescence at 485 nm continuously increased; in contrast, the emission intensity at 674 nm assigned to the CDs remained constant, resulting in the ratiometric sensing of O2·-. The present ratiometric nanoprobe showed high selectivity for O2·- monitoring due to the specific recognition of O2·- by CA. Moreover, the Golgi dots exhibited good linearity with respect to the O2·- concentration within 5 to 40 µM, and the limit of detection (LOD) was ~ 0.13 µM. Additionally, the Golgi dots showed low cytotoxicity and an ability to target the Golgi apparatus. Inspired by these excellent properties, we then applied the Golgi dots to successfully monitor exogenous and endogenous O2·- levels within the Golgi apparatus. Importantly, with the help of Golgi dots, we determined that SD substantially elevated O2·- levels in the brain.

Sleep patterns and quality among Nigerian medical students: A cross-sectional study.

Adequate sleep is crucial for individuals' well-being and cognitive functioning. However, medical students face unique challenges that disrupt their sleep patterns, such as a rigorous curriculum, long study hours, and high-stress levels. Understanding the sleep patterns and quality among medical students in Nigeria is important to develop targeted interventions and support their overall well-being. This study involved 802 medical students from 3 medical schools in Southwest Nigeria. Participants completed an online questionnaire that collected data on their demographic characteristics, sleep patterns and self-reported sleep quality. Descriptive statistics and correlation analysis were used to analyze the data and identify patterns and associations. Most participants were female (56.9%), with the highest representation from the UNILORIN (65.5%). The average reported sleep duration was 5.74 hours per night, indicating insufficient sleep. Irregular bedtimes and wake-up times were commonly reported. A significant proportion of students consumed coffee late at night (27.1%) and used medication to induce sleep (24.3%). Sleep patterns and behaviors, such as snoring (36.1%) and nocturnal eating (57.6%), were reported. Overall, participants reported satisfactory (28.3%) or poor (29.7%) sleep quality. Correlation analysis revealed significant associations between sleep patterns, sleep quality, academic performance, and other sleep-related factors. The study identified insufficient sleep duration, irregular bedtimes, late-night coffee consumption, and poor sleep quality. These findings emphasize the need for interventions and strategies to promote healthy sleep habits among medical students, which can positively impact their overall health and academic performance.

LC-MS/MS analysis of Shenghui decoction component and its effect on learning and memory and neuroprotection in sleep deprivation model mice.

BACKGROUND: In recent years, sleep problems have emerged as a significant factor in the development of diseases that influence cognitive function. The inflammatory response may have a role in the neurobiological processes of sleep deprivation, resulting in impairment of memory and learning. Shenghui Decoction (SHD) is a classic formula in Chinese medicine used to treat forgetfulness and insomnia. However, it remains unclear whether the anti-inflammatory effects of SHD are specifically linked to the inhibition of P2X7R and p38MAPK. METHODS: Analysis of chemical constituents of Shenghui Decoction based on UPLC-Q-TOF-MS / MS. The learning and memory competency of the mice was assessed using the new object recognition and Morris water maze tests. The morphology of hippocampus neurons was observed using HE staining, and the expression of inflammatory factors was measured using ELISA and immunofluorescence. The expression of P2X7R and p38MAPK in the hippocampus was analyzed via real-time PCR and Western blotting. Additionally, the components absorbed into the bloodstream of SHD were analyzed. RESULTS: The study found that SHD contains 47 chemical constituents, including phenolic acids, flavonoids, iridoids, and triterpenoids. In addition, it was observed that SHD significantly improved the learning and memory abilities of the mice. SHD also improved the morphology of hippocampus neurons. The expression of inflammatory factors was decreased in the SHD-treated mice. Additionally, the expression of P2X7R and p38MAPK was decreased in the hippocampus of the SHD-treated mice. Fifteen prototype chemical constituents were detected in blood. CONCLUSIONS: The study suggests that SHD could be a viable treatment for cognitive impairments associated with brain inflammation. The therapeutic effects of SHD are likely due to its chemical components, including phenolic acids, flavonoids, iridoids, and triterpenoids. SHD can improve learning and memory impairment caused by sleep deprivation through the P2X7R/p38MAPK inflammatory signaling pathways.

Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation.

The inverse effects of creatine supplementation and sleep deprivation on high energy phosphates, neural creatine, and cognitive performances suggest that creatine is a suitable candidate for reducing the negative effects of sleep deprivation. With this, the main obstacle is the limited exogenous uptake by the central nervous system (CNS), making creatine only effective over a long-term diet of weeks. Thus far, only repeated dosing of creatine over weeks has been studied, yielding detectable changes in CNS levels. Based on the hypothesis that a high extracellular creatine availability and increased intracellular energy consumption will temporarily increase the central creatine uptake, subjects were orally administered a high single dose of creatinemonohydrate (0.35 g/kg) while performing cognitive tests during sleep deprivation. Two consecutive 31P-MRS scans, 1H-MRS, and cognitive tests were performed each at evening baseline, 3, 5.5, and 7.5 h after single dose creatine (0.35 g/kg) or placebo during sub-total 21 h sleep deprivation (SD). Our results show that creatine induces changes in PCr/Pi, ATP, tCr/tNAA, prevents a drop in pH level, and improves cognitive performance and processing speed. These outcomes suggest that a high single dose of creatine can partially reverse metabolic alterations and fatigue-related cognitive deterioration.

Guhan Yangsheng Jing mitigates hippocampal neuronal pyroptotic injury and manifies learning and memory capabilities in sleep deprived mice via the NLRP3/Caspase1/GSDMD signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Guhan Yangsheng Jing (GHYSJ) is a traditional Chinese patent medicine, that has the function of nourishing the kidney and replenishing the essence, invigorating the brain and calming the mind. It is often used to treat dizziness, memory loss, sleep disorders, fatigue, and weakness, etc. However, its mechanism for improving sleep has not yet been determined. AIM OF THE STUDY: This study aims to explore the effects of GHYSJ on Sleep Deprivation (SD)-induced hippocampal neuronal pyroptotic injury, learning and cognitive abilities, and sleep quality in mice. METHODS: In this study, a PCPA-induced SD mouse model was established. We assessed the influence of GHYSJ on sleep quality and mood by using the pentobarbital-induced sleep test (PIST) and sucrose preference test (SPT). The pharmacological effects of GHYSJ on learning and memory impairment were evaluated by the Morris Water Maze (MWM) and Open Field Test (OFT). Pathological changes in the hippocampal tissue of the SD rats were observed via HE staining and Nissl staining. The severity of neuronal damage was evaluated by detecting the expression of the neuronal marker Microtubule-associated protein 2 (MAP2), via immunohistochemistry and immunofluorescence. Furthermore, the levels of neurotransmitter 5-hydroxytryptophan (5-HTP), 5-hydroxy tryptamine (5-HT), γ-aminobutyric acid (GABA), and Glutamic acid (Glu) in hippocampal tissues, as well as the expression of inflammatory factors Interleukin-1ß (IL-1ß) and Interleukin-18 (IL-18) in serum, were determined by ELISA. The expressions of mRNA and protein NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Cysteinyl aspartate specific proteinase1 (Caspase1), High mobility group box-1 protein (HMGB1) and Apoptosis-associated speck-like protein containing CARD (ASC) related to the cellular ferroptosis pathway were tested and analyzed by RT-PCR and WB respectively. RESULTS: PCPA significantly diminishes the sleep span of experimental animals by expediting the expenditure of 5-HT, consequently establishing an essentially direct SD model. The intervention of GHYSJ displays remarkable efficacy in mitigating insomnia symptoms, encompassing difficulties in initiating sleep and insufficient sleep duration. Likewise, it ameliorates memory function impairments induced by sleep deprivation, along with symptoms such as fatigue and depletion of vitality. GHYSJ exerts a protective influence on hippocampal neurons facilitated by inhibiting the down regulation of MAP2 and maintaining the equilibrium of neurotransmitters (5-HTP, 5-HT, GABA, and Glu). It diminishes the expression of intracellular pyroptosis-associated inflammatory factors (IL-1ß and IL-18) and curbs the activation of the NLRP3/Caspase1/GSDMD pyroptosis-related signaling pathways, thereby alleviating the damage caused by hippocampal neuronal pyroptosis.

Sleep and fatigue management strategies: How nurses, midwives and paramedics cope with their shift work schedules-a qualitative study.

AIMS: To understand the benefits and challenges of shift work, and the coping strategies used by nurses, midwives and paramedics to manage the impact of shift work on sleep and fatigue from shift work. DESIGN: A single case study with embedded units. METHODS: Twenty-seven participants were interviewed exploring their shift work experiences, coping strategies used to improve sleep, and what their recommendations are for improving shift work management. Interviews were completed between November and December 2022. RESULTS: Participants enjoyed the lifestyle, flexibility and financial rewards offered by working shift work. However, fatigue and sleep deprivation undermined these benefits, as it impacted their ability to enjoy social and family events. There were also concerns of long-term health consequences of shift work and delivery of care. Changes to rostering practices and sleep and shift work education were common recommendations. CONCLUSION: This study provides insights on how healthcare professionals manage sleep and fatigue due to shift work and the inadequate support. There is absence of adequate policies, processes and training at an organizational, academic and personal level on how to best manage sleep and fatigue when working shift work. Future research is needed to explore how to equip healthcare shift workers with the skills to successfully manage their schedules to mitigate the negative impact that poor sleep and fatigue has on the health and safety of themselves and their patients. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Understanding the specific challenges of shift work and how workers manage their shift work schedules is critical for improving the health and safety of themselves and their patients. This study identified that there is insufficient training regarding sleep and shift work management strategies, potentially leading to occupational health and safety concerns. Further education and training to equip staff with the necessary information, training and guidance to staff on how to reduce fatigue risk is required. PATIENT OR PUBLIC CONTRIBUTION: This study involved healthcare shift workers in semi-structured interviews. Data gathered from a previous survey that participants were involved in helped shape the interview topics and the study design.

Effects of Supplementing Zinc Magnesium Aspartate on Sleep Quality and Submaximal Weightlifting Performance, following Two Consecutive Nights of Partial Sleep Deprivation.

Purpose: We examined whether supplementation of zinc magnesium aspartate (ZMA), while partially sleep deprived, was beneficial to sleep quality and subsequent morning (07:00 h) submaximal weightlifting. Methods: Using a double-blinded, randomized counterbalanced design, sixteen trained males were recruited and completed six sessions: (i) one repetition max (1 RM) for bench press and back squat; (ii) two familiarisation sessions; (iii) three conditions with 4 h sleep and either: ZMA, placebo (PLA), or NoPill control (NoPill). Submaximal exercise session consisted of three repetitions at 40, 60 and 80% of 1 RM for bench press and back squat. Average power (AP), average velocity (AV), peak velocity (PV), displacement (D) and time-to-peak velocity (tPV) were recorded using MuscleLab linear encoders. Data were analysed using a general linear model with repeated measures and linear correlation. Results: No significant main effect for condition was found for performance values or subjective ratings of fatigue. Main effect for "load" on the bar was found, where AP and tPV values increased with load (p < 0.05). No significant relationship between dose of zinc or magnesium ingested and change in performance for 80% 1 RM power-outputs was found. Conclusion: Supplementation of ZMA for two nights of partial sleep deprivation had no effect on sleep or subsequent morning performance.

Photomodulatory effects in the hypothalamus of sleep-deprived young and aged rats.

Insufficient sleep is associated with impaired hypothalamic activity and declined attentional performance. In this study, alterations in the hypothalamus of REM sleep-deprived (SD) young and aged rats, and the modulatory effect of near-infrared (NIR) laser were investigated. Forty-eight male Wistar rats (24 young at 2 months and 24 senile at 14 months) were divided into three groups: the control, the SD group subjected to 72 hr of sleep deprivation, and the transcranial-NIR laser-treated (TLT) group subjected to SD for 72 hr and irradiated with 830 nm laser. The hypothalamic levels of oxidative stress, inflammatory biomarkers, antioxidant enzymes, mitochondrial cytochrome C oxidase (CCO), apoptotic markers (BAX, BCL-2), and neuronal survival-associated genes (BDNF, GLP-1) were evaluated. Furthermore, the hypothalamic tissue alterations were analyzed via histological examination. The results revealed that TLT treatment has enhanced the antioxidant status, prevented oxidative insults, suppressed neuroinflammation, regulated CCO activity, reduced apoptotic markers, and tuned the survival genes (BDNF & GLP-1) in hypothalamic tissue of SD young and aged rats. Microscopically, TLT treatment has ameliorated the SD-induced alterations and restored the normal histological features of hypothalamus tissue. Moreover, the obtained data showed that SD and NIR laser therapy are age-dependent. Altogether, our findings emphasize the age-dependent adverse effects of SD on the hypothalamus and suggest the use of low-laser NIR radiation as a potential non-invasive and therapeutic approach against SD-induced adverse effects in young and aged animals.

Regulation of stress-induced sleep fragmentation by preoptic glutamatergic neurons.

Sleep disturbances are detrimental to our behavioral and emotional well-being. Stressful events disrupt sleep, in particular by inducing brief awakenings (microarousals, MAs), resulting in sleep fragmentation. The preoptic area of the hypothalamus (POA) is crucial for sleep control. However, how POA neurons contribute to the regulation of MAs and thereby impact sleep quality is unknown. Using fiber photometry in mice, we examine the activity of genetically defined POA subpopulations during sleep. We find that POA glutamatergic neurons are rhythmically activated in synchrony with an infraslow rhythm in the spindle band of the electroencephalogram during non-rapid eye movement sleep (NREMs) and are transiently activated during MAs. Optogenetic stimulation of these neurons promotes MAs and wakefulness. Exposure to acute social defeat stress fragments NREMs and significantly increases the number of transients in the calcium activity of POA glutamatergic neurons during NREMs. By reducing MAs, optogenetic inhibition during spontaneous sleep and after stress consolidates NREMs. Monosynaptically restricted rabies tracing reveals that POA glutamatergic neurons are innervated by brain regions regulating stress and sleep. In particular, presynaptic glutamatergic neurons in the lateral hypothalamus become activated after stress, and stimulating their projections to the POA promotes MAs and wakefulness. Our findings uncover a novel circuit mechanism by which POA excitatory neurons regulate sleep quality after stress.

Melatonin Ameliorates Neuropsychiatric Behaviors, Gut Microbiome, and Microbiota-Derived Metabolites in Rats with Chronic Sleep Deprivation.

With the increasing prevalence of sleep deprivation (SD)-related disorders, the effective treatment of sleep disorders has become a critical health research topic. Thus, we hypothesized and investigated the effectiveness of a 3-week melatonin intervention on neuropsychiatric behavioral responses mediated throughout melatonin receptors, gut microbiota, and lipid metabolites in rats with chronic SD. Eighteen 6-week-old Wistar rats were used and divided into the control grup (C, n = 6), SD group (n = 6), and melatonin-supplemented group (SDM, n = 6). During weeks 0 to 6, animals were provided with the AIN-93M diet and free access to water. Four-week chronic SD was conducted from weeks 7 to 10. Exogenous melatonin administration (10 mg/kg BW) was injected intraperitoneally 1 h before the daily administration of SD for 3 weeks in the SDM group. SD rats exhibited anxiety-like behavior, depression-like behavior, and cognitive impairment. Exogenous melatonin administration ameliorated neuropsychiatric behaviors induced by chronic SD. Analysis of fecal metabolites indicated that melatonin may influence brain messaging through the microbiota-gut-brain axis by increasing the production of short-chain fatty acids (SCFA) and decreasing the production of secondary bile acids (SBA). Four-week SD reduced the cerebral cortex expression of MT1, but not in the colon. Chronic SD led to anxiety and depression-like behaviors and cognitive decline, as well as the reduced intestinal level of SCFAs and the enhanced intestinal level of SBAs in rats. In this work, we confirmed our hypothesis that a 3-week melatonin intervention on neuropsychiatric behavioral response mediated throughout melatonin receptors, gut microbiota, and lipid metabolites in rats with chronic SD.

[Molecular mechanism of sleep deprivation-induced body injury and traditional Chinese medicine prevention and treatment: a review].

Sleep occupies one-third of a person's lifetime and is a necessary condition for maintaining physiological function and health. With the increase in social and economic pressures, the growing use of electronic devices and the accelerated aging process of the population, insufficient sleep and its hazards have drawn widespread attention from researchers in China and abroad. Sleep deprivation refers to a decrease in sleep or a severe lack of sleep due to various reasons. Previous studies have found that sleep deprivation can cause extensive damage to the body, including an increased incidence and mortality rate of neuropathic diseases in the brain, cardiovascular diseases, imbalances in the gut microbiota, and other multi-organ diseases. The mechanisms underlying the occurrence of multi-system and multi-organ diseases due to sleep deprivation mainly involve oxidative stress, inflammatory responses, and impaired immune function in the body. According to traditional Chinese medicine(TCM), sleep deprivation falls into the category of sleepiness, and long-term sleepiness leads to Yin-Yang imbalance, resulting in the consumption of Qi and damage to the five Zang-organs. The appropriate treatment should focus on tonifying deficiency, reinforcing healthy Qi, and harmonizing Yin and Yang. TCM is characterized by a wide variety and abundant resources, and it has minimal side effects and a broad range of applications. Numerous studies have shown that TCM drugs and prescriptions not only improve sleep but also have beneficial effects on liver nourishment, intelligence enhancement, and kidney tonification, effectively preventing and treating the body injury caused by sleep deprivation. Given the increasing prevalence of sleep deprivation and its significant impact on body health, this article reviewed sleep deprivation-mediated body injury and its mechanism, summarized and categorized TCM compound prescriptions and single drugs for preventing and treating body injury, with the aim of laying the foundation for researchers to develop effective drugs for preventing and treating body injury caused by sleep deprivation and providing references for further exploration of the molecular mechanisms underlying the body injury caused by sleep deprivation.

A Randomized, Double-Blind, Placebo-Controlled Decentralized Trial to Assess Sleep, Health Outcomes, and Overall Well-Being in Healthy Adults Reporting Disturbed Sleep, Taking a Melatonin-Free Supplement.

Inadequate sleep is a global health concern. Sleep is multidimensional and complex; new multi-ingredient agents are needed. This study assessed the comparative effects of two multi-ingredient supplements on sleep relative to placebo. Adults (N = 620) seeking better sleep were randomly assigned to receive one of three study products. Sleep A (contained lower (0.35 mg THC and higher levels of botanicals (75 mg each hops oil and valerian oil), Sleep B (contained higher THC (0.85 mg) and lower botanicals (20 mg each hops oil and valerian oil) or placebo) for 4 weeks. Sleep disturbance was assessed at baseline and weekly using NIH's Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A survey. Anxiety, stress, pain, and well-being were assessed using validated measures at baseline and weekly. A linear mixed-effects regression model was used to assess the change in health outcome score between active product groups and the placebo. There was a significant difference in sleep disturbance, anxiety, stress, and well-being between Sleep A and placebo. There was no significant difference in any health parameter between Sleep B and placebo. Side effects were mild or moderate. There were no significant differences in the frequency of side effects between the study groups. A botanical blend containing a low concentration of THC improved sleep disturbance, anxiety, stress, and well-being in healthy individuals that reported better sleep as a primary health concern.

Akkermansia muciniphila supplementation prevents cognitive impairment in sleep-deprived mice by modulating microglial engulfment of synapses.

The microbiome-gut-brain axis plays a crucial role in many neurological diseases, including mild cognitive impairment. Sleep deprivation (SD) induces cognitive decline accompanied by alterations in the gut microbiota. However, the role of gut microbiota alterations in SD-induced cognitive dysfunction and the underlying mechanisms remain unclear. Here, we found that dysbiosis of the gut microbiota following pretreatment with broad-spectrum antibiotics worsens SD-induced cognitive impairment in mice. Fecal microbiota transplantation from SD mice to healthy mice induced cognitive impairment. Additionally, the abundance of Akkermansia muciniphila (A. muciniphila) in the mouse gut microbiota was significantly reduced after 7 days of SD. A. muciniphila pretreatment alleviated cognitive dysfunction and prevented synaptic reduction in the hippocampus in SD mice. A. muciniphila pretreatment inhibited extensive microglial activation and synaptic engulfment in the hippocampus of SD mice. Metabolomics analysis revealed that A. muciniphila pretreatment increased the serum acetate and butanoic acid levels in SD mice. Finally, pretreatment with short-chain fatty acids (SCFAs) inhibited microglial synaptic engulfment and prevented neuronal synaptic loss in SD mice and primary microglia-neuron co-culture following LPS stimulation. Together, our findings illustrate that gut dysbiosis plays an essential role in SD-induced cognitive impairment by activating microglial engulfment at synapses. A. muciniphila supplementation may be a novel preventative strategy for SD-induced cognitive dysfunction, by increasing SCFAs production and maintaining microglial homeostasis.

Low mindfulness is related to poor sleep quality from middle adolescents to emerging adults: a process model involving resilience and emotional dysfunction.

OBJECTIVES: Transitions from middle adolescence into merging adulthood, a life stage between age 15-25, has a high prevalence of sleep problems. Mindfulness is a trait defined as being attentive to the present moment which positively relates to sleep quality. In this study, we aimed to investigate how resilience and emotional dysfunction may influence the relationship between trait mindfulness and sleep quality. METHODS: The Five Facet Mindfulness Questionnaire, Connor-Davidson Resilience Scale, Pittsburgh Sleep Quality Index and Depression Anxiety Stress Scales were used to measure the key variables through an online survey of 497 participants between middle adolescence and emerging adults (317 females, mean age 18.27 ± 0.76 years). A process model was built to investigate the mediating roles of resilience and emotional dysfunction in the impact of trait mindfulness on sleep quality, together with the relationships between their specific components. RESULTS: We found a positive association between mindfulness and sleep quality through resilience and through emotional dysfunction, and through the sequential pathway from resilience to emotional dysfunction. Of note, acting with awareness (mindfulness facet) showed significant indirect effects on sleep quality, mediated by resilience and emotional dysfunction. CONCLUSIONS: Our findings may unveil the underlying mechanisms of how low mindfulness induces poor sleep quality. The findings indicate that conceiving mindfulness as a multifaceted construct facilitates comprehension of its components, relationships with other variables, and underscores its potential clinical significance given its critical implications for mental health.

The effect of 24-hour sleep deprivation and anaerobic exercise on the expression of BAX, BCL2, BMAL1 and CCAR2 genes in peripheral blood mononuclear cells after L-arginine supplementation.

Sleep deprivation disrupt the circadian clock and exercise performance. Defective oxidative stress caused by sleep deprivation may affect the expression of genes involved in cell apoptosis. Since a number of studies have shown the anti-apoptotic effect of L-arginine, so the aim of this study was to evaluate the effect of eight weeks of L-arginine supplementation on the expression of brain and muscle ARNT-like protein 1 (BMAL1), cell cycle and apoptosis regulator 2 (CCAR2), and BAX and BCL2 genes during sleep deprivation and acute anaerobic exercise. Participants included 20 healthy men age 26-35 years, randomized into the L-arginine intervention group (n = 10) and a placebo control (n = 10). The running-based anaerobic sprint test (RAST) was used for anaerobic exercise. Intervention subjects took one 1000 mg L-arginine tablet daily for 8 weeks. The Real-Time PCR method was used to determine apoptosis gene expression in peripheral blood mononuclear cells (PBMCs). Acute anaerobic exercise and sleep deprivation both increased the expression of BAX and CCAR2 genes, and decreased the expression of BCL2 and BMAL1 genes (p < 0.05 for all). L-arginine supplementation increased the expression of BMAL1 and BCL2 genes and decreased the expression of BAX and CCAR2 genes relative to control (p < 0.05). L-Arginine controlled the increase in expression of BAX and CCAR2 genes and the decrease in expression of BCL2 and BMAL1 genes in response to sleep deprivation and acute anaerobic exercise (p < 0.05). Our results showed that 24-hour sleep deprivation and acute anaerobic exercise increased the expression of pro-apoptotic genes (BAX and CCAR2) and decreased the expression of anti-apoptotic genes (BCL2 and BMAL1), although the effect of sleep deprivation is greater. In this situation, L-arginine supplementation may balance the apoptotic state of peripheral blood mononuclear cells. However, any recommendation about this needs further research.

Anandamide improves food intake and orexinergic neuronal activity in the chronic sleep deprivation induction model in rats by modulating the expression of the CB1 receptor in the lateral hypothalamus.

Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. Cannabinoid receptor (CBR) expression in this area is involved in modulating the function of orexin neurons. In this study, we investigated the effects of endocannabinoid anandamide (AEA) administration on improving food intake and appetite by modulating the activity of orexin neurons and CB1R expression after chronic sleep deprivation. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation +20 mg/kg AEA (SD + A). For SD induction, the rats were kept in a sleep deprivation device for 18 h (7 a.m. to 1 a.m.) daily for 21 days. Weight gain, food intake, the electrical power of orexin neurons, CB1R mRNA expression in hypothalamus, CB1R protein expression in the LH, TNF-α, IL-6, IL-4 levels and antioxidant activity in hypothalamus were measured after SD induction. Our results showed that AEA administration significantly improved food intake (p < 0.01), Electrical activity of orexin neurons (p < 0.05), CB1R expression in the hypothalamus (p < 0.05), and IL-4 levels (p < 0.05). AEA also reduced mRNA expression of OX1R and OX2R (p < 0.01 and p < 0.05 respectively), also IL-6 and TNF-α (p < 0.01) and MDA level (p < 0.05) in hypothalamic tissue. As a consequence, AEA modulates orexinergic system function and improves food intake by regulating the expression of the CB1 receptor in the LH in sleep deprived rats.

Modulatory effect of n-3 polyunsaturated fatty acids on depressive-like behaviors in rats with chronic sleep deprivation: potential involvement of melatonin receptor pathway and brain lipidome.

Clinical evidence suggests that a bidirectional relationship is present between sleep loss and psychiatric disorders. Both melatonin receptor agonist ramelteon (RMT) and n-3 polyunsaturated fatty acids (n-3 PUFAs) exhibit antidepressant effects, while their underlying molecular mechanisms might be different. Thus, the present study aims to investigate the add-on effects and possible mechanisms of how RMT and different n-3 PUFAs modulate the melatonin receptor pathway as well as brain lipidome to ameliorate the neuropsychiatric behaviors displayed in rats under chronic sleep deprivation. Thirty-one 6-week-old male Wistar rats were divided into five groups: control (C), sleep deprivation (S), sleep deprivation treated with RMT (SR), sleep deprivation treated with RMT and eicosapentaenoic acid (C20:5n-3, EPA) (SRE), and sleep deprivation treated with RMT and docosahexaenoic acid (C22:6n-3, DHA) (SRD) groups. The results reveal that RMT plus EPA alleviated depressive-like behavior when the rats were subjected to the forced swimming test, whereas RMT plus DHA alleviated anxiety-like behavior when the rats were subjected to the elevated plus maze test. The results of a western blot analysis further revealed that compared with the rats in the S group, those in the SRE and SRD groups exhibited a significantly increased expression of MT2 in the prefrontal cortex, with greater benefits observed in the SRE group. In addition, decreased BDNF and TrkB expression levels were upregulated only in the SRE group. Lipidomic analysis further revealed possible involvement of aberrant lipid metabolism and neuropsychiatric behaviors. RMT plus EPA demonstrated promise as having the effects of reversing the levels of the potential biomarkers of depressive-like behaviors. RMT plus EPA or DHA could ameliorate depressive- and anxiety-like behaviors in sleep-deprived rats through the alteration of the lipidome and MT2 receptor pathway in the brain, whereas EPA and DHA exerted a differential effect.

Fructus gardeniae ameliorates anxiety-like behaviors induced by sleep deprivation via regulating hippocampal metabolomics and gut microbiota.

Fructus gardeniae (FG) is a traditional Chinese medicine and health food for thousands of years of application throughout Chinese history and is still widely used in clinical Chinese medicine. FG has a beneficial impact on anxiety, depression, insomnia, and psychiatric disorders; however, its mechanism of action requires further investigation. This study aimed to investigate the effects and mechanisms of FG on sleep deprivation (SD)-induced anxiety-like behavior in rats. A model of SD-induced anxiety-like behavior in rats was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). This was accompanied by neuroinflammation and metabolic abnormalities in the hippocampus and disturbance of intestinal microbiota. However reduced SD-induced anxiety-like behavior and decreased levels of pro-inflammatory cytokines including TNF-α and IL-1ß were observed in the hippocampus of rats after 7 days of FG intervention. In addition, metabolomic analysis demonstrated that FG was able to modulate levels of phosphatidylserine 18, Phosphatidylinositol 18, sn-glycero-3-phosphocholine, deoxyguanylic acid, xylose, betaine and other metabolites in the hippocampus. The main metabolic pathways of hippocampal metabolites after FG intervention involve carbon metabolism, glycolysis/gluconeogenesis, pentose phosphate, and glycerophospholipid metabolism. 16S rRNA sequencing illustrated that FG ameliorated the dysbiosis of gut microbiota in anxious rats, mainly increased the abundance of Muribaculaceae and Lactobacillus, and decreased the abundance of Lachnospiraceae_NK4A136_group. In addition, the correlation analysis demonstrated that there was a close relationship between hippocampal metabolites and intestinal microbiota. In conclusion, FG improved the anxiety behavior and inhibited of neuroinflammation in sleep-deprived rats, and the mechanism may be related to the FG regulation of hippocampal metabolites and intestinal microflora composition.

Ginsenoside Rg1 alleviates sleep deprivation-induced learning and memory impairment by inhibiting excessive neuronal apoptosis in zebrafish.

Sleep deprivation impairs learning and memory. The neuroprotective function of ginsenoside Rg1 (Rg1) has been reported. This study aimed to investigate the alleviative effect and underlying mechanism of action of Rg1 on learning and memory deficits induced by sleep deprivation. Using 72 h of LED light to establish sleep deprivation model and treatment with Rg1-L (0.5 mg/ml), Rg1-H (1 mg/ml), and melatonin (positive control, 0.25 mg/ml), we investigated the behavioral performance of sleep deprivation zebrafish through 24 h autonomous movement tracking, a novel tank diving test, and a T-maze test. Brain injuries and ultrastructural changes were observed, brain water content was measured, and apoptotic events were analyzed using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. The oxidation-associated biomarkers superoxide dismutase, catalase, and glutathione peroxidase activity and lipid peroxidation product malondialdehyde content were detected. Real-time PCR and western blotting were performed to detect the levels of apoptotic molecules (Bax, caspase-3, and Bcl-2). Rg1-treatment was observed to improve the behavioral performance of sleep-deprivation fish, alleviate brain impairment, and increase oxidative stress-related enzyme activity. Rg1 can effectively exhibit neuroprotective functions and improve learning and memory impairments caused by sleep deprivation, which could be mediated by the Bcl-2/Bax/caspase-3 apoptotic signaling pathway (see Supplementary Video Abstract, Supplemental digital content, http://links.lww.com/WNR/A702 which demonstrates our research objectives, introduction overview of Rg1, and main direction of future research).

Utilizing EEG and fNIRS for the detection of sleep-deprivation-induced fatigue and its inhibition using colored light stimulation.

Drowsy driving is a common, but underestimated phenomenon in terms of associated risks as it often results in crashes causing fatalities and serious injuries. It is a challenging task to alert or reduce the driver's drowsy state using non-invasive techniques. In this study, a drowsiness reduction strategy has been developed and analyzed using exposure to different light colors and recording the corresponding electrical and biological brain activities. 31 subjects were examined by dividing them into 2 classes, a control group, and a healthy group. Fourteen EEG and 42 fNIRS channels were used to gather neurological data from two brain regions (prefrontal and visual cortices). Experiments shining 3 different colored lights have been carried out on them at certain times when there is a high probability to get drowsy. The results of this study show that there is a significant increase in HbO of a sleep-deprived participant when he is exposed to blue light. Similarly, the beta band of EEG also showed an increased response. However, the study found that there is no considerable increase in HbO and beta band power in the case of red and green light exposures. In addition to that, values of other physiological signals acquired such as heart rate, eye blinking, and self-reported Karolinska Sleepiness Scale scores validated the findings predicted by the electrical and biological signals. The statistical significance of the signals achieved has been tested using repeated measures ANOVA and t-tests. Correlation scores were also calculated to find the association between the changes in the data signals with the corresponding changes in the alertness level.