Sleep-wake Cycle Research Articles

Knowledge about sleep-wake cycle and chronobiology by medicine students in Brazil

Knowledge about sleep-wake cycle and chronobiology by medicine students in Brazil

Abstract TP171: Nationwide Diurnal Pattern Among Intracerebral Hemorrhage Incidence and Volume

Introduction: Intracerebral hemorrhage (ICH) incidence follows both seasonal and diurnal patterns noted in the literature. These differences have been attributed to variations in the coagulation cascade, blood pressure, and sleep-wake cycle that all have their own noted rhythmicity. The purpose of this analysis was to validate these trends in a large nationwide database of automated ICH detection scans and evaluate for differences in hematoma volume by image acquisition time. Methods: Serial non-contrast head CT (NCHCT) data, processed with an automated imaging software (iSchemaView), was acquired from U.S. hospitals between 1/1/2020 and 12/31/2021. Final exclusion criteria included: (1) patient age ≤ 25, (2) hematoma volume ≥ 100 ml, (3) hematoma volume ≤ 0.4 ml. Imaging time was subdivided into three epochs: (1) Night: 23:00h-06:59h, (2) Day: 07:00h-14:59h, and (3) Evening: 15:00h-22:59h. Results: A total of 19,397 scans were included in the final analysis with a median ICH volume of 2.9 ml; 15.6% of these scans had volumes above 30 ml. Peak imaging occurred around noon. Hematoma volume was significantly different across timepoints (p = 0.003), with ICHs presenting at night (average volume 14.2 ml) larger than those presenting during the day (12.9 ml, p = 0.002) or evening (13.0 ml, p = 0.012). Conclusion: In this real world, multi-site data set, we show similar diurnal trends in ICH incidence and can detect subtle differences in volume based on time of imaging. Further research is required to elucidate the potential underlying mechanisms for these differences.

The nucleus of solitary tract synchronizes cortical activity through the parabrachial nucleus in sleep-wake cycle in rat

The nucleus of solitary tract synchronizes cortical activity through the parabrachial nucleus in sleep-wake cycle in rat

Sleep wake cycle patterns in infancy are associated with nutritional status in adolescence

Sleep wake cycle patterns in infancy are associated with nutritional status in adolescence

Acute effects of suvorexant on the proportions and architecture of the sleep-wake cycle stages in wild-type rats: induction of narcoleptic traits

Acute effects of suvorexant on the proportions and architecture of the sleep-wake cycle stages in wild-type rats: induction of narcoleptic traits

A case of misaligned clocks and an irregular sleep-wake cycle of an insomniac 9-year old patient with Wolf-Hirschorn syndrome. The rationale for a plausible role of mitochondrial LETM1

A case of misaligned clocks and an irregular sleep-wake cycle of an insomniac 9-year old patient with Wolf-Hirschorn syndrome. The rationale for a plausible role of mitochondrial LETM1

Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations.

Melatonin, an endogenous neurohormone produced by the pineal gland, has received increased interest due to its potential anti-cancer properties. Apart from its well-known role in the sleep-wake cycle, extensive scientific evidence has shown its role in various physiological and pathological processes, such as inflammation. Additionally, melatonin has demonstrated promising potential as an anti-cancer agent as its function includes inhibition of tumorigenesis, induction of apoptosis, and regulation of anti-tumor immune response. Although a precise pathophysiological mechanism is yet to be established, several pathways related to the regulation of cell cycle progression, DNA repair mechanisms, and antioxidant activity have been implicated in the anti-neoplastic potential of melatonin. In the current manuscript, we focus on the potential anti-cancer properties of melatonin and its use in treating and managing pediatric osteosarcoma. This aggressive bone tumor primarily affects children and adolescents and is treated mainly by surgical and radio-oncological interventions, which has improved survival rates among affected individuals. Significant disadvantages to these interventions include disease recurrence, therapy-related toxicity, and severe/debilitating side effects that the patients have to endure, significantly affecting their quality of life. Melatonin has therapeutic effects when used for treating osteosarcoma, attributed to its ability to halt cancer cell proliferation and trigger apoptotic cell death, thereby enhancing chemotherapeutic efficacy. Furthermore, the antioxidative function of melatonin alleviates harmful side effects of chemotherapy-induced oxidative damage, aiding in decreasing therapeutic toxicities. The review concisely explains the many mechanisms by which melatonin targets osteosarcoma, as evidenced by significant results from several in vitro and animal models. Nevertheless, if further explored, human trials remain a challenge that could shed light and support its utility as an adjunctive therapeutic modality for treating osteosarcoma.

Single-cell transcriptomics reveals that glial cells integrate homeostatic and circadian processes to drive sleep–wake cycles

The sleep–wake cycle is determined by circadian and sleep homeostatic processes. However, the molecular impact of these processes and their interaction in different brain cell populations are unknown. To fill this gap, we profiled the single-cell transcriptome of adult Drosophila brains across the sleep–wake cycle and four circadian times. We show cell type-specific transcriptomic changes, with glia displaying the largest variation. Glia are also among the few cell types whose gene expression correlates with both sleep homeostat and circadian clock. The sleep–wake cycle and sleep drive level affect the expression of clock gene regulators in glia, and disrupting clock genes specifically in glia impairs homeostatic sleep rebound after sleep deprivation. These findings provide a comprehensive view of the effects of sleep homeostatic and circadian processes on distinct cell types in an entire animal brain and reveal glia as an interaction site of these two processes to determine sleep–wake dynamics.

Functional hierarchies in brain dynamics characterized by signal reversibility in ferret cortex.

Brain signal irreversibility has been shown to be a promising approach to study neural dynamics. Nevertheless, the relation with cortical hierarchy and the influence of different electrophysiological features is not completely understood. In this study, we recorded local field potentials (LFPs) during spontaneous behavior, including awake and sleep periods, using custom micro-electrocorticographic (μECoG) arrays implanted in ferrets. In contrast to humans, ferrets remain less time in each state across the sleep-wake cycle. We deployed a diverse set of metrics in order to measure the levels of complexity of the different behavioral states. In particular, brain irreversibility, which is a signature of non-equilibrium dynamics, captured by the arrow of time of the signal, revealed the hierarchical organization of the ferret's cortex. We found different signatures of irreversibility and functional hierarchy of large-scale dynamics in three different brain states (active awake, quiet awake, and deep sleep), showing a lower level of irreversibility in the deep sleep stage, compared to the other. Irreversibility also allowed us to disentangle the influence of different cortical areas and frequency bands in this process, showing a predominance of the parietal cortex and the theta band. Furthermore, when inspecting the embedded dynamic through a Hidden Markov Model, the deep sleep stage was revealed to have a lower switching rate and lower entropy production. These results suggest functional hierarchies in organization that can be revealed through thermodynamic features and information theory metrics.

Drosophila melanogaster models of MPS IIIC (Hgsnat-deficiency) highlight the role of glia in disease presentation.

Sanfilippo syndrome (Mucopolysaccharidosis type III or MPS III) is a recessively inherited neurodegenerative lysosomal storage disorder. Mutations in genes encoding enzymes in the heparan sulphate degradation pathway lead to the accumulation of partially degraded heparan sulphate, resulting ultimately in the development of neurological deficits. Mutations in the gene encoding the membrane protein heparan-α-glucosaminide N-acetyltransferase (HGSNAT; EC2.3.1.78) cause MPS IIIC (OMIM#252930), typified by impaired cognition, sleep-wake cycle changes, hyperactivity and early death, often before adulthood. The precise disease mechanism that causes symptom emergence remains unknown, posing a significant challenge in the development of effective therapeutics. As HGSNAT is conserved in Drosophila melanogaster, we now describe the creation and characterisation of the first Drosophila models of MPS IIIC. Flies with either an endogenous insertion mutation or RNAi-mediated knockdown of hgsnat were confirmed to have a reduced level of HGSNAT transcripts and age-dependent accumulation of heparan sulphate leading to engorgement of the endo/lysosomal compartment. This resulted in abnormalities at the pre-synapse, defective climbing and reduced overall activity. Altered circadian rhythms (shift in peak morning activity) were seen in hgsnat neuronal knockdown lines. Further, when hgsnat was knocked down in specific glial subsets (wrapping, cortical, astrocytes or subperineural glia), impaired climbing or reduced activity was noted, implying that hgsnat function in these specific glial subtypes contributes significantly to this behaviour and targeting treatments to these cell groups may be necessary to ameliorate or prevent symptom onset. These novel models of MPS IIIC provide critical research tools for delineating the key cellular pathways causal in the onset of neurodegeneration in this presently untreatable disorder.

The potential and prospects of sleep biomarkers in early Alzheimer's disease diagnosis

Alzheimers disease (AD), often accompanied by sleep disturbances, is a neurodegenerative disease. Sleep disruptions have the potential to serve as biomarkers for early diagnosis because they can be observed in the initial stages of disease progression in the sleep-wake cycle. This paper summarizes the latest findings on AD manifestations during non-rapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, sleep oscillations, and cognitive impairment. It provides a detailed overview of diagnostic bioindicators for primary Alzheimers disease, including invasive cerebrospinal fluid (CSF) markers, non-invasive electroencephalography (EEG), and plasma biomarkers, and compares their advantages and limitations in diagnosing early AD. The accuracy and reliability of sleep biomarkers in early diagnosis are evaluated, along with their clinical application prospects. The paper also proposes improvements in the use of sleep clinical markers for early Alzheimers disease diagnosis, aiming for greater breakthroughs in this field. The significance of this review lies in its in-depth exploration of the association between sleep disturbances and the early period of the disease, along with the introduction of potential biomarkers that can serve as tools for early determining and monitoring of this neurodegenerative health issue.

Impact of the circadian clock on cardiovascular physiology and pathophysiology

Circadian rhythms are the innate approximately 24-hour oscillations that orchestrate a multitude of physiological processes encompassing sleep-wake cycles, hormone secretion, thermoregulation, metabolism, and behavioral patterns. Also, those rhythms are intrinsically governed by the suprachiasmatic nucleus (SCN) ensconced in the anterior hypothalamic region. The SCN, synchronized during daylight hours receives and transmits diverse bodily signals to calibrate physiological dynamics, and imbue disturbances with potential repercussions reverberating across a plethora of physiological and behavioral domains. Previous studies have proven that the diurnal changes in the circadian rhythm multiple myocardial processes and have a critical impact on the physiology and pathophysiology of the cardiovascular system. This comprehensive review emphasizes the profound influence of circadian rhythms, orchestrated by the suprachiasmatic nucleus, on cardiovascular health. It reveals that disruptions in circadian rhythms impact blood pressure, myocardial function, platelet responsiveness, and the autonomic nervous system, all of which are critical for cardiovascular well-being. The significance of this research lies in its potential to guide interventions for cardiovascular disease prevention and management, particularly in the context of modern challenges like shift work. Understanding this intricate relationship is crucial for safeguarding cardiovascular health in our fast-paced world.

Sleep In Infants –A Pilot Study In North Karnataka

Background: Normal growth and development, emotional wellness, and immune function all require adequate sleep. Sleep is commonly thought to be a time when the mind and body relax and recover, but in reality, sleep is a period of significant neuronal and physiological activity. This study intends to find the prevalence of sleep disturbance in typically developing infants.Methodology:The study included 60 participants. The parents of the participants who met the study criteriawere administered a questionnaire including demographic details of the child and questions pertaining to the sleep behaviour of their child during the first 12 months of life. The data collected was subjected to appropriate statistical analysis.Result: The study included 60 participants of either gender in the age group of 12-24 months. The mean birthweight of all the children was 2891.6 (±553.9) grams. The mean age of sleep development of all participants was 4.18 (±2.61) months. Pearson’s correlation analysis revealed that there was no statistical significance between mother’s age at delivery and birth weights or sleep development age of children. Also,the birth weight and sleep development age of children didn’t correlate with each other.A large number [50(83%)] of children developed the sleep pattern by 6 months of age, which was significant at a z-value of 7.303 at p-value of <0.00001.Discussion: The mean birth weight of boys was higher than the girls. The boys also developed the circadiansleep wake cycle slightly later than girls. However, no significant correlation was found between birth weights and sleep development ages of children. Majority of the infants developed the sleep rhythm in first 6 months of life whereas a small proportion developed it later till 12 months of age.Conclusion: The boys developed the circadian sleep wake cycle slightly later than the girls. However,maximumchildren developed the sleep pattern by 6 months.

Crosstalk between the subiculum and sleep-wake regulation: A review.

The circuitry underlying the initiation, maintenance, and coordination of wakefulness, rapid eye movement sleep, and non-rapid eye movement sleep is not thoroughly understood. Sleep is thought to arise due to decreased activity in the ascending reticular arousal system, which originates in the brainstem and awakens the thalamus and cortex during wakefulness. Despite the conventional association of sleep-wake states with hippocampal rhythms, the mutual influence of the hippocampal formation in regulating vigilance states has been largely neglected. Here, we focus on the subiculum, the main output region of the hippocampal formation. The subiculum, particulary the ventral part, sends extensive monosynaptic projections to crucial regions implicated in sleep-wake regulation, including the thalamus, lateral hypothalamus, tuberomammillary nucleus, basal forebrain, ventrolateral preoptic nucleus, ventrolateral tegmental area, and suprachiasmatic nucleus. Additionally, second-order projections from the subiculum are received by the laterodorsal tegmental nucleus, locus coeruleus, and median raphe nucleus, suggesting the potential involvement of the subiculum in the regulation of the sleep-wake cycle. We also discuss alterations in the subiculum observed in individuals with sleep disorders and in sleep-deprived mice, underscoring the significance of investigating neuronal communication between the subiculum and pathways promoting both sleep and wakefulness.

Interaction modes of human orexin 2 receptor with selective and nonselective antagonists studied by NMR spectroscopy

Orexin neuropeptides have many physiological roles in the sleep-wake cycle, feeding behavior, reward demands, and stress responses by activating cognitive receptors, the orexin receptors (OX1R and OX2R), distributed in the brain. There are only subtle differences between OX1R and OX2R in the orthosteric site, which has hindered the rational development of subtype-selective antagonists. In this study, we utilized solution-state NMR to capture the structural plasticity of OX2R labeled with 13CH3-ε-methionine in complex with antagonists. Mutations in the orthosteric site allosterically affected the intracellular tip of TM6. Ligand exchange experiments with the subtype-selective EMPA and the nonselective suvorexant identified three methionine residues that were substantially perturbed. The NMR spectra suggested that the suvorexant-bound state exhibited more structural plasticity than the EMPA-bound state, which has not been foreseen from the close similarity of their crystal structures, providing insights into dynamic features to be considered in understanding the ligand recognition mode.

Behavior and physiology in female Cricetulus barabensis are associated with the expression of circadian genes.

The circadian clock regulates the behavior, physiology, and metabolism of mammals, and these characteristics, such as sleep-wake cycles, exercise capacity, and hormone levels, exhibit circadian rhythms. Light signaling is the main stimulator of the mammalian circadian system. The photoperiod regulates the reproductive cycle of seasonal breeding animals, and the circadian clock plays a pivotal role in this process. However, the role of the clock in coordinating animal behavior and physiology in response to photoperiodic changes needs further investigation. The present study investigated the changes and correlation of behavioral activities, physiological indicators, and gene expression in female striped hamsters (Cricetulus barabensis) within 24 h under a 12L:12D photoperiod. We found that the daily rhythms of sleep-wake and open field were significant in hamsters. The expression of clock genes, melatonin receptor genes, and genes involved in general metabolism oscillated significantly in central and peripheral tissues (brain, hypothalamus, liver, ovary, and thymus) and was significantly associated with behavior and physiology. Our results revealed that the neuroendocrine system regulated the rhythmicity of behavior and physiology, and central and peripheral clock genes (Bmal1, Clock, Per1, Per2, Cry1, and Cry2), melatonin receptor genes (MT1, MT2, and GPR50), and metabolizing genes (SIRT1, FGF21, and PPARα) played important roles. Our results suggest that central and peripheral circadian clocks, melatonin receptors, and genes involved in general metabolism may play key roles in maintaining circadian behavior and metabolic homeostasis in striped hamsters. Our results may have important implication for rodent pest control.

Protective role of madecassoside from Centella asiatica against protein L-isoaspartyl methyltransferase deficiency-induced neurodegeneration

Protein L-isoaspartyl methyltransferase (PIMT/PCMT1) could repair l-isoaspartate (L-isoAsp) residues formed by deamidation of asparaginyl (Asn) residues or isomerization of aspartyl (Asp) residues in peptides and proteins during aging. Aside from abnormal accumulation of L-isoAsp, PIMT knockout (KO) mice mirrors some neuropathological hallmarks such as anxiety-like behaviors, impaired spatial memory and aberrant synaptic plasticity in the hippocampus of neurodegenerative diseases (NDs), including Alzheimer's disease (AD) and related dementias, and Parkinson's disease (PD). While some reports indicate the neuroprotective effect of madecassoside (MA) as a triterpenoid saponin component of Centella asiatica, its role against NDs-related anxiety and cognitive impairment remains unclear. Therefore, we investigated the effect of MA against anxiety-related behaviors in PIMT deficiency-induced mouse model of NDs. Results obtained from the elevated plus maze (EPM) test revealed that MA treatment alleviated anxiety-like behaviors in PIMT knockout mice. Furthermore, Real-time PCR, electroencephalogram (EEG) recordings, transmission electron microscopy analysis and ELISA were carried out to evaluate the expression of clock genes, sleep and synaptic function, respectively. The PIMT knockout mice were characterized by abnormal clock patterns, sleep disturbance and synaptic dysfunction, which could be improved by MA administration. Collectively, these findings suggest that MA exhibits neuroprotective effects associated with improved circadian rhythms sleep-wake cycle and synaptic plasticity in PIMT deficient mice, which could be translated to ameliorate anxiety-related symptoms and cognitive impairments in NDs.

ПСИХОЛОГИЧЕСКИЕ ОСОБЕННОСТИ АДАПТАЦИИ ОРГАНИЗМА ЗДОРОВОГО ЧЕЛОВЕКА К МОДЕЛИРУЕМЫМ ФАКТОРАМ КОСМИЧЕСКОГО ПОЛЕТА В ЭКСПЕРИМЕНТЕ С 21-СУТОЧНОЙ «СУХОЙ» ИММЕРСИЕЙ

The 21-d dry immersion study with participation of 8 male volunteers at the age of 25 to 33 years included investigations of the psychological aspects of adaptation to simulated spaceflight factors. Psychological testing 14 days prior to DI and on day 21 of the study was performed using the multilevel adaptivity inventory (А.G. Maklakova and S.V. Chermianina), the inventory of mental activity, interests, affective tone, strain and comfort (L.A. Kurgansky and Т.А. Nemchina), well-being in extreme conditions inventory (А. Volkova and N.E. Vodopianova) and situation-adaptable subjective vitality scale (R. Rayan and S. Frederick, apecialized by L.A. Aleksandrova). Participants in the study adapted successfully to the conditions as could be deduced from stability of their personal adaptation potential. At the end of the study the participants were noted to be more neurotic, demonstrated symptoms of autonomic regulation imbalance, disorders in the sleep wakefulness cycles, psychological discomfort and reduction of the energy potential. These changes witnessed to a moderate stress reaction to the DI conditions.

The role of cerebral activation in the sleep-wake cycle

The development of views on cerebral activation in the wakefulness-sleep cycle, starting with the work of Constantin von Economo, is considered. The emphasis is on the cyclic activation of high-amplitude discharges in sleep, which, with known assumptions, can include K-complexes, as well as patterns of delta-like waves. Considering the participation of the peripheral nervous system in this, the integrative role of cyclic activation of high-amplitude discharges in the organization of the sleep-wake cycle is discussed.

Misalignment of Circadian Rhythms in Diet-Induced Obesity.

The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronize them with daily cycles. While the central clock in the suprachiasmatic nucleus (SCN) is mainly synchronized by the light/dark cycles, the peripheral clocks react to other stimuli, including the feeding/fasting state, nutrients, sleep-wake cycles, and physical activity. During the disruption of circadian rhythms due to genetic mutations or social and occupational obligations, incorrect arrangement between the internal clock system and environmental rhythms leads to the development of obesity. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition leads to uncoupling of the peripheral clocks from the central pacemaker and to the development of metabolic disorders. The strong coupling of the SCN to the light-dark cycle creates a situation of misalignment when food is ingested during the "wrong" time of day. Food-anticipatory activity is mediated by a self-sustained circadian timing, and its principal component is a food-entrainable oscillator. Modifying the time of feeding alone greatly affects body weight, whereas ketogenic diet (KD) influences circadian biology, through the modulation of clock gene expression. Night-eating behavior is one of the causes of circadian disruption, and night eaters have compulsive and uncontrolled eating with severe obesity. By contrast, time-restricted eating (TRE) restores circadian rhythms through maintaining an appropriate daily rhythm of the eating-fasting cycle. The hypothalamus has a crucial role in the regulation of energy balance rather than food intake. While circadian locomotor output cycles kaput (CLOCK) expression levels increase with high-fat diet-induced obesity, peroxisome proliferator-activated receptor-alpha (PPARα) increases the transcriptional level of brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like 1 (BMAL1) in obese subjects. In this context, effective timing of chronotherapies aiming to correct SCN-driven rhythms depends on an accurate assessment of the SCN phase. In fact, in a multi-oscillator system, local rhythmicity and its disruption reflects the disruption of either local clocks or central clocks, thus imposing rhythmicity on those local tissues, whereas misalignment of peripheral oscillators is due to exosome-based intercellular communication.Consequently, disruption of clock genes results in dyslipidemia, insulin resistance, and obesity, while light exposure during the daytime, food intake during the daytime, and sleeping during the biological night promote circadian alignment between the central and peripheral clocks. Thus, shift work is associated with an increased risk of obesity, diabetes, and cardiovascular diseases because of unusual eating times as well as unusual light exposure and disruption of the circadian rhythm.