BACKGROUND: This study explored how acute sleep deprivation (ASD) before myocardial ischemia influences oxytocin release from paraventricular (PVN) neurons and its correlation with sympathetic nervous system (SNS) activity post-acute sleep loss, impacting subsequent left ventricular (LV) remodeling following myocardial infarction (MI).
METHODS: The study was conducted in two phases: induction of ASD, inducing MI, blood sampling, euthanizing animals and collecting their heart and brain for histological and gene expression evaluations. The animals in first and second phase were euthanized 24 h and 14 days after MI, respectively.
RESULTS: Pre-MI ASD, accompanied by increased serum epinephrine levels within 24 h of MI, upregulated oxytocin and cFos expression in the PVN. Also, pre-MI ASD resulted in decreased serum PAB levels 14 days post-MI (P < 0.001). While notable echocardiographic changes were seen in MI versus sham groups, ASD demonstrated protective effects. This was evidenced by reduced infarct size, elevated TIMP1, MMP2, and MMP9 in the LV of SD + MI animals versus MI alone (P < 0.05). Additionally, histological analysis showed reduced LV fibrosis in pre-MI ASD subjects (P < 0.05).
CONCLUSIONS: Our study supports the notion that activation of oxytocin neurons within the PVN subsequent to ASD interacts with autonomic centers in the central nervous system. This enhanced sympathetic outflow to the heart prior to MI triggers a preconditioning response, thereby mediating cardioprotection through decreased oxidative stress biomarkers and regulated extracellular matrix (ECM) turnover.

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.

Brain function is vulnerable to the consequences of inadequate sleep, an adverse trend that is increasingly prevalent. The REM sleep phase has been implicated in coordinating various brain structures and is hypothesized to have potential links to brain variability. However, traditional imaging research have encountered challenges in attributing specific brain region activity to REM sleep, remained understudied at the whole-brain connectivity level. Through the spilt-night paradigm, distinct patterns of REM sleep phases were observed among the full-night sleep group (n = 36), the early-night deprivation group (n = 41), and the late-night deprivation group (n = 36). We employed connectome-based predictive modeling (CPM) to delineate the effects of REM sleep deprivation on the functional connectivity of the brain (REM connectome) during its resting state. The REM sleep-brain connectome was characterized by stronger connectivity within the default mode network (DMN) and between the DMN and visual networks, while fewer predictive edges were observed. Notably, connections such as those between the cingulo-opercular network (CON) and the auditory network, as well as between the subcortex and visual networks, also made significant contributions. These findings elucidate the neural signatures of REM sleep loss and reveal common connectivity patterns across individuals, validated at the group level.

The association between sleep and the immune-endocrine system is well recognized, but the nature of that relationship is not well understood. Sleep fragmentation induces a pro-inflammatory response in peripheral tissues and brain, but it also activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing glucocorticoids (GCs) (cortisol in humans and corticosterone in mice). It is unclear whether this rapid release of glucocorticoids acts to potentiate or dampen the inflammatory response in the short term. The purpose of this study was to determine whether blocking or suppressing glucocorticoid activity will affect the inflammatory response from acute sleep fragmentation (ASF). Male C57BL/6J mice were injected i.p. with either 0.9% NaCl (vehicle 1), metyrapone (a glucocorticoid synthesis inhibitor, dissolved in vehicle 1), 2% ethanol in polyethylene glycol (vehicle 2), or mifepristone (a glucocorticoid receptor antagonist, dissolved in vehicle 2) 10 min before the start of ASF or no sleep fragmentation (NSF). After 24 h, samples were collected from brain (prefrontal cortex, hypothalamus, hippocampus) and periphery (liver, spleen, heart, and epididymal white adipose tissue (EWAT)). Proinflammatory gene expression (TNF-α and IL-1β) was measured, followed by gene expression analysis. Metyrapone treatment affected pro-inflammatory cytokine gene expression during ASF in some peripheral tissues, but not in the brain. More specifically, metyrapone treatment suppressed IL-1β expression in EWAT during ASF, which implies a pro-inflammatory effect of GCs. However, in cardiac tissue, metyrapone treatment increased TNF-α expression in ASF mice, suggesting an anti-inflammatory effect of GCs. Mifepristone treatment yielded more significant results than metyrapone, reducing TNF-α expression in liver (only NSF mice) and cardiac tissue during ASF, indicating a pro-inflammatory role. Conversely, in the spleen of ASF-mice, mifepristone increased pro-inflammatory cytokines (TNF-α and IL-1β), demonstrating an anti-inflammatory role. Furthermore, irrespective of sleep fragmentation, mifepristone increased pro-inflammatory cytokine gene expression in heart (IL-1β), pre-frontal cortex (IL-1β), and hypothalamus (IL-1β). The results provide mixed evidence for pro- and anti-inflammatory functions of corticosterone to regulate inflammatory responses to acute sleep loss.

BACKGROUND: Global nursing shortages necessitate the identification of mitigatable factors that may reduce nursing absence and turnover. Fatigue has been shown to be associated with these issues. This study aimed to identify factors leading to development of or recovery from excessive fatigue in nurses as these can offer actionable avenues for protecting nurses against fatigue or supporting fatigue recovery.
METHODS: A longitudinal study among nurses randomly sampled from the Norwegian Nurse\'s Organization. The Chalder Fatigue Questionnaire measured fatigue. Dichotomized scoring was used, with scores ≥ 4 considered excessive fatigue. The study included questions on shift work schedules, psychosocial work characteristics, sleep, body mass index, physical activity, caffeine, alcohol, mental health, etc. Two sets of logistic regression analysis were conducted (one for development of and one for recovery from excessive fatigue), evaluating how changes in work, lifestyle and health between baseline (2015) and follow-up (2018) affected first, odds of development of excessive fatigue and second, odds of recovery from excessive fatigue.
RESULTS: Among 1,311 included nurses, 21.6% maintained, 13.3% developed, and 18.0% recovered from excessive fatigue (2015-2018). Within work characteristics, increased psychological work demands were associated with development of excessive fatigue OR = 1.77 (CI = 1.11-2.82). Several work characteristics were associated with recovery from excessive fatigue, including decreased decision latitude (OR = 0.39; CI = 0.19-0.82) and increased coworker support (OR = 1.90; CI = 1.11-3.24). Shift work variables were not associated with fatigue outcomes. Amongst lifestyle factors, changes in sleep duration, obesity, and exercise were significant. Notably, developing inappropriate sleep duration (OR = 2.84; CI = 1.47-5.48) increased odds of developing excessive fatigue, while maintaining inappropriate sleep duration (< 6 h or > 8 h) (OR = 0.19; CI = 0.54-0.65) decreased odds of recovering. All assessed health conditions (depression, anxiety, insomnia, and shift work disorder) were related to development of (ORs 2.10-8.07) or recovery from (ORs 0.10-0.50) excessive fatigue. Depression, for example, increased odds of development of (OR = 8.07; CI = 2.35-27.66) and decreased odds of recovery (OR = 0.10; CI = 0.04-0.26) from excessive fatigue.
CONCLUSIONS: Changes in lifestyle factors, health conditions, and psychosocial work factors were associated with development of and recovery from excessive fatigue. Sleep and psychosocial work factors played important roles. We found no relationship with shift work schedules.

Sleep disturbances and persistent pain conditions are public health challenges worldwide. Although it is well-known that sleep deficit increases pain sensitivity, the underlying mechanisms remain elusive. We have recently demonstrated the involvement of nucleus accumbens (NAc) and anterior cingulate cortex (ACC) in the pronociceptive effect of sleep restriction. In this study, we found that sleep restriction increases c-Fos expression in NAc and ACC, suggesting hyperactivation of these regions during prolonged wakefulness in male Wistar rats. Blocking adenosine A2A receptors in the NAc or GABAA receptors in the ventral tegmental area (VTA), dorsal raphe nucleus (DRN), or locus coeruleus (LC) effectively mitigated the pronociceptive effect of sleep restriction. In contrast, the blockade of GABAA receptors in each of these nuclei only transiently reduced carrageenan-induced hyperalgesia. Pharmacological activation of dopamine D2, serotonin 5-HT1A and noradrenaline alpha-2 receptors within the ACC also prevented the pronociceptive effect of sleep restriction. While pharmacological inhibition of these same monoaminergic receptors in the ACC restored the pronociceptive effect which had been prevented by the GABAergic disinhibition of the of the VTA, DRN or LC. Overall, these findings suggest that the pronociceptive effect of sleep restriction relies on increased adenosinergic activity on NAc, heightened GABAergic activity in VTA, DRN, and LC, and reduced inhibitory monoaminergic activity on ACC. These findings advance our understanding of the interplay between sleep and pain, shedding light on potential NAc-brainstem-ACC mechanisms that could mediate increased pain sensitivity under conditions of sleep impairment.

Rationale: Currently, there are occasional reports of health problems caused by sleep deprivation (SD). However, to date, there remains a lack of in-depth research regarding the effects of SD on the growth and development of oocytes in females. The present work aimed to investigate whether SD influences ovarian folliculogenesis in adolescent female mice. Methods: Using a dedicated device, SD conditions were established in 3-week old female mice (a critical stage of follicular development) for 6 weeks and gut microbiota and systemic metabolomics were analyzed. Analyses were related to parameters of folliculogenesis and reproductive performance of SD females. Results: We found that the gut microbiota and systemic metabolomics were severely altered in SD females and that these were associated with parameters of premature ovarian insufficiency (POI). These included increased granulosa cell apoptosis, reduced numbers of primordial follicles (PmFs), correlation with decreased AMH, E2, and increased LH in blood serum, and a parallel increased number of growing follicles and changes in protein expression compatible with PmF activation. SD also reduced oocyte maturation and reproductive performance. Notably, fecal microbial transplantation from SD females into normal females induced POI parameters in the latter while niacinamide (NAM) supplementation alleviated such symptoms in SD females. Conclusion: Gut microbiota and alterations in systemic metabolomics caused by SD induced POI features in juvenile females that could be counteracted with NAM supplementation.

BACKGROUND: Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO.
METHODS: Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods.
RESULTS: The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor.
CONCLUSIONS: Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.

OBJECTIVE: To compare the effect of stage 3 fragmentation and the paradoxical phase of night sleep on melatonin (MT) secretion, and to evaluate the effects of changes in autonomic balance and activation reactions that occur in the orthodox and paradoxical phases of sleep.
METHODS: Fifteen healthy men participated in three sessions: with stage 3 fragmentation, with fragmentation of paradoxical sleep, and in a control experiment in which sleep was not disturbed. In each experiment, 7 saliva samples were collected in the evening, at night and in the morning and the MT content was determined. Heart rate variability was analyzed using an electrocardiogram and autonomic balance was assessed.
RESULTS: Sleep fragmentation was accompanied by activation reactions and reduced the duration of stage 3 and paradoxical phase sleep by 50% and 51% in the corresponding sessions. Fragmentation of paradoxical sleep also led to an increase in the duration of night wakefulness. Sleep disturbances caused an increase in MT secretion in the second half of the night and in the morning, especially pronounced in sessions with fragmentation of paradoxical sleep, in which upon awakening MT was 1.8 times higher than in the control. Stage 3 fragmentation was accompanied by increased sympathetic activation, while fragmentation of paradoxical sleep did not cause autonomic shifts. The subjects were divided into 2 clusters: with high and low MT in night and morning saliva samples. In all sessions, subjects with high MT had 1.7-2 times longer duration of night wakefulness; in sessions with fragmentation, they had significantly more activations in the paradoxical phase of sleep.
CONCLUSIONS: Night sleep disturbances cause an increase in MT secretion, especially pronounced during the fragmentation of the paradoxical phase. An increase in MT levels does not depend on changes in autonomic balance and is apparently associated with activation of the serotonergic system, which accompanies disturbances in the depth and continuity of sleep.
UNASSIGNED: Сравнить влияние на секрецию мелатонина (МТ) фрагментации 3-й стадии и парадоксальной фазы ночного сна, а также оценить эффекты изменений вегетативного баланса и реакций активации, возникающих в ортодоксальной и парадоксальной фазах сна.
UNASSIGNED: Пятнадцать здоровых мужчин участвовали в трех экспериментах: с фрагментацией 3-й стадии, с фрагментацией парадоксального сна, и в контрольном, в котором сон не нарушался. В каждом эксперименте вечером, ночью и утром собирали 7 проб слюны и определяли содержание МТ. По электрокардиограмме анализировали вариабельность сердечного ритма и оценивали вегетативный баланс.
UNASSIGNED: Фрагментация сна сопровождалась реакциями активации и снизила продолжительность 3-й стадии и парадоксальной фазы сна на 50 и 51% в соответствующих экспериментах. Фрагментация парадоксального сна привела также к увеличению продолжительности ночного бодрствования. Нарушения сна вызывали рост секреции МТ во второй половине ночи и утром, особенно выраженный в экспериментах с фрагментацией парадоксального сна, в которых при пробуждении МТ был в 1,8 раза выше, чем в контроле. Фрагментация 3-й стадии сопровождалась усилением симпатической активации, тогда как фрагментация парадоксального сна не вызывала вегетативных сдвигов. Испытуемые разделились на 2 кластера: с высоким и низким МТ в ночных и утренних пробах слюны. Испытуемые с высоким МТ имели во всех экспериментах в 1,7—2 раза большую продолжительность ночного бодрствования, в экспериментах с фрагментацией у них было значительно больше активаций в парадоксальной фазе сна.
UNASSIGNED: Нарушения ночного сна вызывают рост секреции МТ, особенно выраженный при фрагментации парадоксальной фазы. Повышение уровня МТ не зависит от изменений вегетативного баланса и, по-видимому, связано с активацией серотонинергической системы, сопровождающей нарушение глубины и непрерывности сна.

Sleep deficiency is a rampant issue in modern society, serving as a pathogenic element contributing to learning and memory impairment, with heightened sensitivity observed in children. Clinical observations suggest that learning disabilities associated with insufficient sleep during adolescence can persist through adulthood, but experimental evidence for this is lacking. In this study, we examined the impact of early-life sleep deprivation on both short-term and long-term memory, tracking the effects sequentially into adulthood. We employed a modified multiple platform method (MMPM) mouse model to investigate these outcomes. Sleep deprivation induced over a 14-day period, beginning on postnatal day 28 (PND28) in mice, led to significant impairment in long-term memory (while short-term memory remained unaffected) at PND42. Notably, this dysfunction persisted into adulthood at PND85. The specific impairment observed in long-term memory was elucidated through histopathological alterations in hippocampal neurogenesis, as evidenced by bromodeoxyuridine (BrdU) signals, observed both at PND42 and PND85. Furthermore, the hippocampal region exhibited significantly diminished protein expressions of astrocyte, characterized by lowered levels of aquaporin 4 (AQP4), a representative molecule involved in brain clearance processes, and reduced protein expressions of brain-derived neurotrophic factor (BDNF). In conclusion, we have presented experimental evidence indicating that sleep deficiency-related impairment of long-term memory in adolescence can endure into adulthood. The corresponding mechanisms may indicate that the modification of astrocyte-related molecules has led to changes in hippocampal neurogenesis.