Subclinical hypomanic experiences in young adults after sleep deprivation are independent of depressive disorders, chronotype or 5-HTTLPR polymorphism.

INTRODUCTION: The acute antidepressant effect of sleep deprivation (SD) in patients with depressive disorders has been studied for more than 60 years. However, hypomanic mood swings after partial or total SD have also been described in people without diagnosed mental disorders. Studying this phenomenon in the general population may yield insights about the mechanisms of therapeutic SD, mania and bipolar disorders. METHODS: A cross-sectional sample of young adults was recruited and classified into those who described having regularly occurring subclinical hypomanic experiences (ROHE) after SD and those who did not. History of psychiatric and physical illness, with screening for depression and mania, as well as alcohol or drug consumption, family history of depressive disorders or suicide, 5-HTTLPR polymorphism, and MEQ-SA chronotype were collected. RESULTS: A total of 251 participants were included; 39.0% indicated regularly having subclinical hypomanic experiences after SD. These experiences were not associated with depressive or mania screening, history of psychiatric illness, family history, 5-HTTLPR polymorphism, or MEQ-SA chronotype. CONCLUSIONS: ROHE after non-therapeutic SD seem to be a relatively common phenomenon in young adults, independent of depressive mood state. Our results suggest that therapeutic SD may depend on a physiological phenomenon of subclinical affective disturbance after SD that affects a part of the general population, independent of psychiatric diagnosis. Further studies could elucidate associated factors and contribute to our understanding of (hypo-)manic mood states.

Mechanisms, Consequences and Role of Interventions for Sleep Deprivation: Focus on Mild Cognitive Impairment and Alzheimer's Disease in Elderly.

Sleep is established as an essential physiological need that impacts physical, emotional, and cognitive functions profoundly. Physiologically, inadequate sleep weakens immune function, heightening susceptibility to infections and chronic illnesses such as obesity, diabetes, and cardiovascular diseases. Hormonal disruptions due to sleep loss further exacerbate metabolic dysregulation, contributing to weight gain and other health complications. Emotionally, sleep deprivation leads to mood disturbances, including increased irritability, heightened stress responses, and a greater likelihood of mood disorders like depression and anxiety. These effects are compounded by cognitive impairments such as reduced alertness, impaired memory consolidation, and compromised decision-making abilities, akin to the impairments caused by alcohol consumption. Motor skills and coordination also suffer, elevating the risk of accidents, particularly in high-stress environments. For older adults, sleep quality is closely linked to cognitive function and overall longevity. Optimal sleep patterns are associated with slower brain aging and improved health outcomes. However, sleep disorders exacerbate existing conditions such as epilepsy and asthma, necessitating interventions like cognitive behavioral therapy (CBT) and medications such as melatonin to mitigate their impact. Education emerges as a crucial tool in promoting healthier sleep habits across all age groups. Addressing misconceptions about sleep and integrating sleep health into public health policies are essential steps toward improving overall well-being. Additionally, lifestyle factors such as diet and physical activity play significant roles in regulating sleep patterns, further emphasizing the interconnectedness of sleep with broader health outcomes. In summary, the articles underscore the intricate mechanisms through which sleep influences physiological functions and advocate for comprehensive approaches to enhance sleep hygiene and mitigate the adverse effects of sleep deprivation on human health.

Human serum proteomics reveals a molecular signature after one night of sleep deprivation.

Study Objectives: Sleep deprivation is highly prevalent and caused by conditions such as night shift work or illnesses like obstructive sleep apnea. Compromised sleep affects cardiovascular-, immune-, and neuronal systems. Recently, we published human serum proteome changes after a simulated night shift. This pilot proteomic study aimed to further explore changes in human blood serum after 6 hours of sleep deprivation at night. Methods: Human blood serum samples from eight self-declared healthy females were analyzed using Orbitrap Eclipse mass spectrometry (MS-MS) and high-pressure liquid chromatography. We used a within-participant design, in which the samples were taken after 6 hours of sleep at night and after 6 hours of sleep deprivation the following night. Systems biological databases and bioinformatic software were used to analyze the data and comparative analysis were done with other published sleep-related proteomic datasets. Results: Out of 494 proteins, 66 were found to be differentially expressed proteins (DEPs) after 6 hours of sleep deprivation. Functional enrichment analysis revealed the associations of these DEPs with several biological functions related to the altered regulation of cellular processes such as platelet degranulation and blood coagulation, as well as associations with different curated gene sets. Conclusions: This study presents serum proteomic changes after 6 hours of sleep deprivation, supports previous findings showing that short sleep deprivation affects several biological processes, and reveals a molecular signature of proteins related to pathological conditions such as altered coagulation and platelet function, impaired lipid and immune function, and cell proliferation. Data are available via ProteomeXchange with identifier PXD045729. This paper is part of the Genetic and other molecular underpinnings of sleep, sleep disorders, and circadian rhythms including translational approaches Collection.

Impact of chronic sleep deprivation on male reproductive health: Insights from testicular and epididymal responses in mice.

BACKGROUND: Sleep deprivation (SD) can cause damage to the male reproductive system. However, the duration required for such damage and the specific sequence and severity of damage to the testis and epididymis remain unclear. OBJECTIVE: To investigate the effects of different durations of SD on different parts of the testis and epididymis caput, corpus, and cauda. METHODS: Adult ICR mice were randomly assigned to five groups: the SD group (SD for 18 h/day for 1, 2, 3, or 4 weeks), the SD + Vit E group (supplemented with Vit E 50 mg/kg/d during 4 weeks of SD, the SD+NS group (saline supplementation during 4 weeks of SD), the SD + RS group (5 weeks of recovery sleep after 4 weeks of SD), and a normal sleep control (Ctrl) group. Following the interventions, sperm parameters, testicular and epididymal histopathology, inflammatory response, and oxidative stress markers were compared between the groups. RESULTS: Compared to the Ctrl group, the SD group showed a decrease in sperm motility and concentration from SD 2 W and SD 3 W, respectively. Decreases in sperm concentration and motility were more pronounced in the cauda compared to the caput and corpus. Pathological damage was less severe in the epididymis caput than in the corpus and cauda. After 4 weeks of SD, inflammation and oxidative stress increased in both testes and epididymis. Both sleep recovery and vitamin E supplementation showed significant improvements, though they did not fully reach the level of the Ctrl group. CONCLUSION: Chronic SD for more than 2 weeks causes varying degrees of damage to the testis, epididymis caput, corpus, and cauda in male mice. This damage is not fully reversible after 5 weeks of sleep recovery and antioxidant stress treatment. These findings help us to identify and prevent SD damage to the male reproduction at an early stage.

Protective effects of a probiotic-fermented germinated grain complex on neurotransmitters and sleep quality in sleep-deprived mice.

Objective: To explore the effects of probiotic fermentation products of germinated grains on cognitive and sleep improvement in mice with sleep deprivation induced by chlorophenylalanine (PCPA), and to provide theoretical and experimental basis for the development of natural products to alleviate insomnia. Methods: ELISA and high-performance liquid chromatography (HPLC) were used to determine the contents of γ-aminobutyric acid and L-theanine in fermentation products. Open Field Test was used to analyze the changes of emotional behavior between groups before and after intervention. ELISA was used to analyze the changes of hypothalamic serotonin, GABA, glutamate, and serum interleukin 6. 16S rRNA sequencing was used to analyze the changes of intestinal flora before and after the intervention of compound fermentation products. LC-MS/MS was used to analyze the changes of intestinal SCFAs before and after the intervention. Results: The content of GABA and L-theanine in 7 L fermentation products was 12.555 µmol/L (1.295 mg/L) and 0.471 mg/mL by ELISA. Compared with the PCPA-induced Model group, the sleep duration of the KEY group was statistically significant (p < 0.0001). Compared with the PCPA-induced Model group, the number of crossing the central lattice in the KEY group was significantly increased, and the number of grooming was significantly reduced (all p < 0.05), suggesting that the anxiety behavior of the mice was improved. In addition, this study found that the compound fermentation products could significantly increase the content of neurotransmitters such as 5-HT, GABA and Glu in the hypothalamus of mice, reduce the content of inflammatory factors such as IL-6, IL-1ß and TNF-α in serum, regulate the structure of intestinal flora and increase the content of short-chain fatty acids. Conclusion: Probiotic fermentation products of germinated grains can significantly improve sleep deprivation in PCPA mice, which may be related to regulating the levels of neurotransmitters and inflammatory factors, improving the structure of intestinal flora, and increasing the content of short-chain fatty acids. This study provides new candidates and research directions for the development of natural drugs to alleviate insomnia.

Caffeine and modafinil modulate the effects of sleep deprivation on thalamic resting-state functional connectivity: A double-blind pilot study.

BACKGROUND: Studies have found that the use of clinically approved caffeine and modafinil can alleviate cognitive impairment due to sleep deprivation (SD) to some extent. However, the neural mechanisms by which these two cognitive enhancers work to counteract the effects of SD on cognitive impairment remain unclear. METHODS: A double-blind within-subjects experiment using resting-state functional magnetic resonance imaging (rs-fMRI) was designed. Participants underwent three 36-h SD trials, each of which involved taking 200 mg of caffeine, modafinil, or placebo at the 28th and 32 nd h of SD. Sixteen subregions of the thalamus were selected as the regions of interest and changes in functional connectivity (FC) between the thalamus and the other brain regions were explored after the participants took caffeine or modafinil. RESULTS: The subjective sleepiness of the participants increased with the duration of SD. compared with placebo, modafinil and caffeine had insignificant effects on wakefulness or sleepiness. However, in terms of neural FC, we found varying degrees of attenuation or enhancement of the FC between the thalamus and other regions. Taking caffeine during SD weakened the FC between the right rostral temporal thalamus (rTtha) subregion and the left lingual gyrus compared with placebo. Caffeine enhanced the FC between three subregions of the thalamus, namely the left sensory thalamus, the left rTtha, and the right lateral pre-frontal thalamus, and the right inferior temporal, left orbitofrontal, and right superior occipital gyris. Modafinil weakened the FC between the right posterior parietal thalamus and left middle temporal gyrus, and enhanced the FC between the left medial pre-frontal thalamus, left rTtha, and right occipital thalamus and left middle frontal gyrus. CONCLUSIONS: After 36 h of total SD, modafinil and caffeine administration enhanced or attenuated the time-domain correlations between various subregions of the thalamus and brain regions of the frontal and temporal lobes in healthy adults, compared with placebo. These results provide valuable evidence for further unraveling the neuropharmacological mechanisms of caffeine and modafinil, as well as important insights for exploring effective pharmacological intervention strategies against SD.

Altered Functional Connectivity of the Thalamus Subregions Associated with Impaired Attention After Sleep Deprivation.

Objective: The thalamus plays a critical role in attentional maintenance. Previous studies have revealed the dysfunction of the thalamus in attention decline after acute sleep deprivation (SD). However, the functional connectivity (FC) between the thalamus subregions and cortical regions underlying attentional impairment after acute SD remains unclear. Here, we aimed to probe the relationship between attentional function and the altered thalamocortical FC after acute SD. Methods: In this study, 25 healthy participants with regular sleep conducted an attentional network test and received a resting-state fMRI scan before and after 24 hours of SD. Then, we analyzed the FC between the thalamus and cerebrum and relationships with attentional function in the enrolled subjects. Results: Our results showed that the participants showed a significantly lower alerting effect, a higher executive effect, and lower accuracy after acute SD. Compared to the rested wakefulness state, we observed decreased FCs between the "somatosensory" thalamic seed and left frontal pole, right frontal pole, left middle temporal gyrus (posterior division), and right middle temporal gyrus (posterior division). Furthermore, the reduced FC between the right middle temporal gyrus and "somatosensory" thalamic seed was negatively associated with the change in orienting effect of the participants. Conclusion: Our findings reveal that the disrupted FC between thalamus subregions and cortical regions may contribute to impaired attention after SD.

Melatonin modulates TLR4/MyD88/NF-κB signaling pathway to ameliorate cognitive impairment in sleep-deprived rats.

Sleep deprivation (SD) is commonplace in today's fast-paced society. SD is a severe public health problem globally since it may cause cognitive decline and even neurodegenerative disorders like Alzheimer's disease. Melatonin (MT) is a natural chemical secreted by the pineal gland with neuroprotective effects. The purpose of this study was to investigate the protective effect and mechanism of MT on chronic sleep deprivation-induced cognitive impairment. A 3-week modified multi-platform method was used to create the SD rat model. The Morris water maze test (MWM), Tissue staining (including Hematoxylin and Eosin (H & E) staining, Nissl staining, and immunofluorescence), Western blot, Enzyme-linked immunosorbent assay (ELISA), and Quantitative real-time polymerase chain reaction (qPCR) were used to investigate the protective effect and mechanism of MT in ameliorating cognitive impairment in SD rats. The results showed that MT (50 and 100 mg/kg) significantly improved cognitive function in rats, as evidenced by a shortening of escape latency and increased time of crossing the platform and time spent in the quadrant. Additionally, MT therapy alleviated hippocampus neurodegeneration and neuronal loss while lowering levels of pathogenic factors (LPS) and inflammatory indicators (IL-1ß, IL-6, TNF-α, iNOS, and COX2). Furthermore, MT treatment reversed the high expression of Aß42 and Iba1 as well as the low expression of ZO-1 and occludin, and inhibited the SD-induced TLR4/MyD88/NF-κB signaling pathway. In summary, MT ameliorated spatial recognition and learning memory dysfunction in SD rats by reducing neuroinflammation and increasing neuroprotection while inhibiting the TLR4/MyD88/NF-κB signaling pathway. Our study supports the use of MT as an alternate treatment for SD with cognitive impairment.

Assessing the influence of sleep and sampling time on metabolites in oral fluid: implications for metabolomics studies.

INTRODUCTION: The human salivary metabolome is a rich source of information for metabolomics studies. Among other influences, individual differences in sleep-wake history and time of day may affect the metabolome. OBJECTIVES: We aimed to characterize the influence of a single night of sleep deprivation compared to sufficient sleep on the metabolites present in oral fluid and to assess the implications of sampling time points for the design of metabolomics studies. METHODS: Oral fluid specimens of 13 healthy young males were obtained in Salivette® devices at regular intervals in both a control condition (repeated 8-hour sleep) and a sleep deprivation condition (total sleep deprivation of 8 h, recovery sleep of 8 h) and their metabolic contents compared in a semi-targeted metabolomics approach. RESULTS: Analysis of variance results showed factor 'time' (i.e., sampling time point) representing the major influencer (median 9.24%, range 3.02-42.91%), surpassing the intervention of sleep deprivation (median 1.81%, range 0.19-12.46%). In addition, we found about 10% of all metabolic features to have significantly changed in at least one time point after a night of sleep deprivation when compared to 8 h of sleep. CONCLUSION: The majority of significant alterations in metabolites' abundances were found when sampled in the morning hours, which can lead to subsequent misinterpretations of experimental effects in metabolomics studies. Beyond applying a within-subject design with identical sample collection times, we highly recommend monitoring participants' sleep-wake schedules prior to and during experiments, even if the study focus is not sleep-related (e.g., via actigraphy).

Sleep deprivation effects on brain state dynamics are associated with dopamine D2 receptor availability via network control theory.

BACKGROUND: Sleep deprivation (SD) negatively affects brain function. Most brain imaging studies have investigated the effects of SD on 'static' brain function. SD effects on functional brain dynamics and their relationship with molecular changes remain relatively unexplored. METHODS: We used functional MRI to examine resting brain state dynamics after one night of SD compared to rested wakefulness (RW) and assessed their association with striatal brain dopamine D2 receptor availability (D2R) measured by PET-[11C]raclopride using network control theory. RESULTS: SD reduced dwell time and persistence probabilities with the strongest effects in two brain states, one characterized by high default mode network and low dorsal attention network activity and the other by high frontal parietal network and low somatomotor network activity. Using network control theory, we showed that after SD there was an overall increase in the control energy required for brain state transitions with effects varying for different brain state transitions. Control energy requirement was negatively associated with transition probabilities under SD and RW and accounted for SD-induced changes in transition probabilities. Alteration in the energy landscape was associated with SD-induced changes in striatal D2R distribution. CONCLUSIONS: These findings demonstrate altered occurrence of internally and externally oriented brain states following acute SD and suggest an association with energy requirements for brain state transitions modulated by striatal D2R.

Acute sleep deprivation-induced hepatotoxicity and dyslipidemia in middle-aged female rats and its amelioration by butanol extract of Tinospora cordifolia.

BACKGROUND: Sleep deprivation (SD) due to an unhealthy lifestyle poses an oxidative challenge and is closely associated with an increased risk and prevalence of different metabolic disorders. Although the negative consequences of SD are well reported on mental health little is known about its detrimental effects on liver function and lipid metabolism. Tinospora cordifolia is reported for its hepatoprotective activity in different pre-clinical model systems. The current study was designed to elucidate the cumulative effects of aging and acute SD on liver functions, oxidative stress, and lipid metabolism, and their management by butanol extract of T. cordifolia (B-TCE) using middle-aged female acyclic rats as the model system. RESULTS: Rats were divided into 4 groups: (1) Vehicle-undisturbed (VUD) (2) Vehicle-sleep deprived (VSD) (3) B-TCE pre-treated sleep-deprived (TSD) (4) B-TCE pre-treated undisturbed sleep (TUD). TSD and TUD groups were given 35 mg/kg of B-TCE once daily for 15 days followed by 12 h of sleep deprivation (6 a.m.-6 p.m.) of VSD and TSD group animals using the gentle-handling method while VUD and TUD group animals were left undisturbed. SD of VSD group animals increased oxidative stress, liver function disruption, and dyslipidemia which were ameliorated by B-TCE pre-treatment. Further, B-TCE was observed to target AMPK and its downstream lipid metabolism pathways as well as the p-Akt/cyclinD1/p-bad pathway of cell survival as possible underlying mechanisms of its hepatoprotective activity. CONCLUSIONS: These findings suggest that B-TCE being a multi-component extract may be a potential agent in curtailing sleep-related problems and preventing SD-associated hepatotoxicity and dyslipidemia in postmenopausal women.

Sleep maintains excitatory synapse diversity in the cortex and hippocampus.

Insufficient sleep is a global problem with serious consequences for cognition and mental health.1 Synapses play a central role in many aspects of cognition, including the crucial function of memory consolidation during sleep.2 Interference with the normal expression or function of synapse proteins is a cause of cognitive, mood, and other behavioral problems in over 130 brain disorders.3 Sleep deprivation (SD) has also been reported to alter synapse protein composition and synapse number, although with conflicting results.4,5,6,7 In our study, we conducted synaptome mapping of excitatory synapses in 125 regions of the mouse brain and found that sleep deprivation selectively reduces synapse diversity in the cortex and in the CA1 region of the hippocampus. Sleep deprivation targeted specific types and subtypes of excitatory synapses while maintaining total synapse density (synapse number/area). Synapse subtypes with longer protein lifetimes exhibited resilience to sleep deprivation, similar to observations in aging and genetic perturbations. Moreover, the altered synaptome architecture affected the responses to neural oscillations, suggesting that sleep plays a vital role in preserving cognitive function by maintaining the brain's synaptome architecture.

Neuroelectrophysiological alteration associated with cognitive flexibility after 24 h sleep deprivation in adolescents.

The cognitive neural mechanisms by which sleep deprivation affects cognitive flexibility are poorly understood. Therefore, the study investigated the neuroelectrophysiological basis of the effect of 24 h sleep deprivation on cognitive flexibility in adolescents. 72 participants (36 females, mean age ± SD=20.46 ± 2.385 years old) participated in the study and were randomly assigned to the sleep deprivation group and control group. They were instructed to complete a task switch paradigm, during which participants' behavioral and electroencephalographic data were recorded. Behaviorally, there were significant between-group differences in accuracy. The results of event-related potential showed that the P2, N2 and P3 components had significant group effects or interaction effects. At the time-frequency level, there were statistically significant differences between the delta and theta bands. These results suggested that 24 h sleep deprivation affected problem-solving effectiveness rather than efficiency, mainly because it systematically impaired cognitive processing associated with cognitive flexibility.

Orexin-mediated Motivated Arousal and Reward Seeking.

The neuromodulator orexin has been identified as a key factor for motivated arousal including recent evidence that sleep deprivation-induced enhancement of reward behavior is modulated by orexin. While orexin is not necessary for either reward or arousal behavior, orexin neurons' broad projections, ability to sense the internal state of the animal, and high plasticity of signaling in response to natural rewards and drugs of abuse may underlie heightened drug seeking, particularly in a subset of highly motivated reward seekers. As such, orexin receptor antagonists have gained deserved attention for putative use in addiction treatments. Ongoing and future clinical trials are expected to identify individuals most likely to benefit from orexin receptor antagonist treatment to promote abstinence, such as those with concurrent sleep disorders or high craving, while attention to methodological considerations will aid interpretation of the numerous preclinical studies investigating disparate aspects of the role of orexin in reward and arousal.

Modulating the Pronociceptive Effect of Sleep Deprivation: A Possible Role for Cholinergic Neurons in the Medial Habenula.

Sleep deprivation has been shown to exacerbate pain sensitivity and may contribute to the onset of chronic pain, yet the precise neural mechanisms underlying this association remain elusive. In our study, we explored the contribution of cholinergic neurons within the medial habenula (MHb) to hyperalgesia induced by sleep deprivation in rats. Our findings indicate that the activity of MHb cholinergic neurons diminishes during sleep deprivation and that chemogenetic stimulation of these neurons can mitigate the results. Interestingly, we did not find a direct response of MHb cholinergic neurons to pain stimulation. Further investigation identified the interpeduncular nucleus (IPN) and the paraventricular nucleus of the thalamus (PVT) as key players in the pro-nociceptive effect of sleep deprivation. Stimulating the pathways connecting the MHb to the IPN and PVT alleviated the hyperalgesia. These results underscore the important role of MHb cholinergic neurons in modulating pain sensitivity linked to sleep deprivation, highlighting potential neural targets for mitigating sleep deprivation-induced hyperalgesia.

Cyclooxygenase-2 (COX-2)-dependent mechanisms mediate sleep responses to microbial and thermal stimuli.

Prostaglandins (PGs) play a crucial role in sleep regulation, yet the broader physiological context that leads to the activation of the prostaglandin-mediated sleep-promoting system remains elusive. In this study, we explored sleep-inducing mechanisms potentially involving PGs, including microbial, immune and thermal stimuli as well as homeostatic sleep responses induced by short-term sleep deprivation using cyclooxygenase-2 knockout (COX-2 KO) mice and their wild-type littermates (WT). Systemic administration of 0.4 µg lipopolysaccharide (LPS) induced increased non-rapid-eye movement sleep (NREMS) and fever in WT animals, these effects were completely absent in COX-2 KO mice. This finding underscores the essential role of COX-2-dependent prostaglandins in mediating sleep and febrile responses to LPS. In contrast, the sleep and fever responses induced by the pro-inflammatory cytokine tumor necrosis factor α, a proinflammatory cytokine which activates COX-2, were preserved in COX-2 KO animals, indicating that these effects are independent of COX-2-related signaling. Additionally, we examined the impact of ambient temperature on sleep. The sleep-promoting effects of moderate warm ambient temperature were suppressed in COX-2 KO animals, resulting in significantly reduced NREMS at ambient temperatures of 30 °C and 35 °C compared to WT mice. However, rapid-eye-movement sleep responses to moderately cold or warm temperatures did not differ between the two genotypes. Furthermore, 6 h of sleep deprivation induced rebound increases in sleep with no significant differences observed between COX-2 KO and WT mice. This suggests that while COX-2-derived prostaglandins are crucial for the somnogenic effects of increased ambient temperature, the homeostatic responses to sleep loss are COX-2-independent. Overall, the results highlight the critical role of COX-2-derived prostaglandins as mediators of the sleep-wake and thermoregulatory responses to various physiological challenges, including microbial, immune, and thermal stimuli. These findings emphasize the interconnected regulation of body temperature and sleep, with peripheral mechanisms emerging as key players in these integrative processes.

Predicting long-term sleep deprivation using wearable sensors and health surveys.

Sufficient sleep is essential for individual well-being. Inadequate sleep has been shown to have significant negative impacts on our attention, cognition, and mood. The measurement of sleep from in-bed physiological signals has progressed to where commercial devices already incorporate this functionality. However, the prediction of sleep duration from previous awake activity is less studied. Previous studies have used daily exercise summaries, actigraph data, and pedometer data to predict sleep during individual nights. Building upon these, this article demonstrates how to predict a person's long-term average sleep length over the course of 30 days from Fitbit-recorded physical activity data alongside self-report surveys. Recursive Feature Elimination with Random Forest (RFE-RF) is used to extract the feature sets used by the machine learning models, and sex differences in the feature sets and performances of different machine learning models are then examined. The feature selection process demonstrates that previous sleep patterns and physical exercise are the most relevant kind of features for predicting sleep. Personality and depression metrics were also found to be relevant. When attempting to classify individuals as being long-term sleep-deprived, good performance was achieved across both the male, female, and combined data sets, with the highest-performing model achieving an AUC of 0.9762. The best-performing regression model for predicting the average nightly sleep time achieved an R-squared of 0.6861, with other models achieving similar results. When attempting to predict if a person who previously was obtaining sufficient sleep would become sleep-deprived, the best-performing model obtained an AUC of 0.9448.

Geraniol (GER) attenuated chronic sleep restriction (CSR)-induced neuroinflammation in adolescent mice.

Sleep insufficiency is a significant health problem worldwide, and adolescent sleep restriction (SR) could induce multiple neurodevelopmental disorders in the central nervous system (CNS). Microglial-mediated neuroinflammation plays a vital role in multiple neurological diseases, and recent research showed the regulation effect of immunoproteasome on microglia functions. Geraniol (GER), an important ingredient in many essential oils, possesses diverse pharmacological properties like anti-inflammatory and antioxidant. The present study was designed to evaluate the neuroprotective effect of GER on SR in adolescent mice and further investigate the underlying mechanisms. Our results displayed that 14 days of chronic sleep restriction (CSR) induced cognitive decline, and anxiety-like and attention-deficit behaviors, which were mitigated by GER pretreatment. GER administration also reversed microglial pro-inflammatory response under CSR stimulation in the anterior cingulate cortex (ACC) regions by reducing the expression and secretion of cytokines like IL-1ß and TNF-α. Mechanism research showed that LMP7 mRNA was selectively up-regulated under CSR treatment but down-regulated by GER administration. Proteasome activity and protein expression of LMP7 were consistent with mRNA data. ONX-0914 was applied to inhibit LMP7 selectively, and data validated that GER might alleviate CSR-induced neuroinflammation by regulating LMP7. Our study provides evidence that LMP7 is a critical regulator of CSR-induced proinflammation, and geraniol might be a promising therapy against CSR-induced neurodevelopmental disorders.

Propofol improves sleep deprivation-induced sleep structural and cognitive deficits via upregulating the BMAL1 expression and suppressing microglial M1 polarization.

BACKGROUND: Sleep deprivation (SD) is a growing global health problem with many deleterious effects, such as cognitive impairment. Microglia activation-induced neuroinflammation may be an essential factor in this. Propofol has been shown to clear sleep debt after SD in rats. This study aims to evaluate the effects of propofol-induced sleep on ameliorating sleep quality impairment and cognitive decline after 48 h SD. METHODS: Almost 8-12-week-old rats were placed in the SD system for 48 h of natural sleep or continuous SD. Afterwards, rats received propofol (20 mg·kg-1·h-1, 6 h) via the tail or slept naturally. The Morris water maze (MWM) and Y-maze test assessed spatial learning and memory abilities. Rat EEG/EMG monitored sleep. The expression of brain and muscle Arnt-like protein 1 (BMAL1), brain-derived neurotrophic factor (BDNF) in the hippocampus and BMAL1 in the hypothalamus were assessed by western blot. Enzyme-linked immunosorbent assay detected IL-6, IL-1ß, arginase 1 (Arg1), and IL-10 levels in the hippocampus. Immunofluorescence was used to determine microglia expression as well as morphological changes. RESULTS: Compared to the control group, the sleep-deprived rats showed poor cognitive performance on both the MWM test and the Y-maze test, accompanied by disturbances in sleep structure, including increased total sleep time, and increased time spent and delta power in non-rapid eye movement sleep. In addition, SD induces abnormal expression of the circadian rhythm protein BMAL1, activates microglia, and causes neuroinflammation and nerve damage. Propofol reversed these changes and saved sleep and cognitive impairment. Furthermore, propofol treatment significantly reduced hippocampal IL-1ß and IL-6 levels, increased BDNF, Arg1, and IL-10 levels, and switched microglia surface markers from the inflammatory M1 type to the anti-inflammatory M2 type. CONCLUSION: Propofol reduces SD-induced cognitive impairment and circadian rhythm disruption, possibly by lowering neuronal inflammation and switching the microglia phenotype from an M1 to an M2 activated state, thus exerting neuroprotective effects.