Materiały źródłowe

• #1 Editorial: The pathogenesis and intervention of sleep disorders

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10174448/

  Sleep disorders are a growing concern that affects a significant portion of the population and can lead to severe health consequences, including depression, anxiety, and cardiovascular disease. […] The pathogenesis of sleep disorders is complex and multifactorial, involving both genetic and environmental factors. Therefore, understanding the mechanisms of sleep disorders and identifying effective interventions is crucial for improving diagnosis and treatment. […] These findings suggest that disrupted cerebellar-prefrontal cortical pathways may contribute to cognitive impairment in OSA patients, highlighting the importance of early detection and treatment of OSA to prevent further cognitive decline. […] This study suggests that targeting the gut microbiota may be a promising approach for managing sleep disorders in patients with TBI.

• #1 Sleep Disorders

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/neurology/sleep-disorders/

  Normal sleep and wake states are generated by a complex neuronal network in the brain and are regulated by homeostatic and circadian mechanisms. Sleep may be divided into 2 main stages: rapid eye movement (REM) and non-REM (NREM) sleep. REM sleep is also known as paradoxical sleep because it resembles wakefulness with desynchronized electroencephalography (EEG) activity, phasic events such as REM, and bursts of muscle activity. REM sleep also is characterized by dreaming. NREM sleep is characterized by synchronized EEG activity, muscle relaxation, and decreased heart rate, blood pressure, and tidal volume. […] Sleep physiology changes with age as the brain matures and eventually degenerates. With advancing age, there is a decline in the percentage of sleep that is deep, more frequent awakenings, and sleep fragmentation. In the elderly, sleep disorders such as obstructive sleep apnea (OSA) occur more frequently. Sleep needs also vary with age, decreasing from 16 hours a day in infancy and stabilizing at 7 to 8 hours for most normal adults. […] Sleep deprivation creates a sleep debt that must be repaid, resulting in compensatory heightened pressure to sleep and eventual increased sleep intensity and duration. Conversely, excessive sleep reduces sleep propensity and amount of sleep.

• #1 Sleep-Wake Disorders: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/287104-overview

  Sleep disorders may be primary or may result from a variety of psychiatric and medical conditions. […] Primary sleep disorders result from an endogenous disturbance in sleep-wake generating or timing mechanisms, often complicated by behavioral conditioning. […] Disturbances in the pattern and periodicity of REM and NREM sleep are often found when people admit to experiencing sleep disorders. […] Sleep-wake cycles are governed by a complex group of biologic processes that serve as internal clocks. […] Multiple neurotransmitters are thought to play a role in sleep. […] Abnormalities in the delicate balance of all of these chemical messenger systems may disrupt various physiologic, biologic, behavioral, and EEG parameters responsible for REM (ie, active) sleep and NREM (slow-wave) sleep.

• #1 Key mechanism behind sleep discovered: Finding holds promise for treatment of fatigue and sleep disorders | ScienceDaily

  https://www.sciencedaily.com/releases/2010/09/100914100302.htm

  Washington State University researchers have discovered the mechanism by which the brain switches from a wakeful to a sleeping state. […] The mechanism — a cascade of chemical transmitters and proteins — opens the door to a more detailed understanding of the sleep process and possible targets for drugs and therapies aimed at the costly, debilitating and dangerous problems of fatigue and sleeplessness. […] The researchers documented how ATP (adenosine triphosphate), the fundamental energy currency of cells, is released by active brain cells to start the molecular events leading to sleep. […] By charting the link between ATP and the sleep regulatory substances, the researchers have found the way in which the brain keeps track of activity and ultimately switches from a wakeful to sleeping state. […] Sleep disorders like insomnia can be viewed as being caused by some parts of the brain being awake while other parts are asleep, giving rise to new therapies. […] The link between sleep, brain cell activity and ATP has many practical consequences, Krueger said.

• #1 Insomnia Overview: Epidemiology, Pathophysiology, Diagnosis and Monitoring, and Nonpharmacologic Therapy

  https://www.ajmc.com/view/insomnia-overview-epidemiology-pathophysiology-diagnosis-and-monitoring-and-nonpharmacologic-therapy

  Insomnia is a complex interaction of psychological cognitive arousal and altered circadian and homeostatic mechanisms. Decreased function of the sleep-wake switch may also contribute to insomnia. During sleep, there is a slow transition through stages of nonrapid-eye movement (non-REM) sleep to cycles of rapid-eye movement (REM) sleep. Multiple brain centers work in concert to promote sleep or wakefulness. The sleep-wake cycle is a complex process in which wakefulness and sleep are switched on and off by reciprocal systems in a feedback loop. Wakefulness results from ascending activity in a number of brainstem and posterior hypothalamic nuclei in what is referred to as the ascending reticular activation system (ARAS). This system projects widely into the cerebral cortex. Hypocretin/orexin-containing neurons in the lateral hypothalamus (orexin) project to hypothalamic and brainstem arousal centers and functionally reinforce their activity during wakefulness.

• #1 Insomnia Overview: Epidemiology, Pathophysiology, Diagnosis and Monitoring, and Nonpharmacologic Therapy

  https://www.ajmc.com/view/insomnia-overview-epidemiology-pathophysiology-diagnosis-and-monitoring-and-nonpharmacologic-therapy

  This model of the sleep-wake cycle is often called the flip-flop switch because it permits one to either be awake or asleep, but not both, at the same time. Via the switching mechanism, the active state suppresses the other state until circadian rhythms induce a switch to the reciprocal state. The cerebral cortex and the limbic system further modify wakefulness. Sleep-promoting centers in the anterior hypothalamus project into the brainstem and posterior arousal centers and function with the lateral hypothalamus as a sleep-wake switch. […] Circadian factors promote wakefulness on a roughly 24-hour biological clock, whereas homeostatic factors respond to accumulated wakefulness with the drive for sleep. In the brain, the ARAS promotes wakefulness and the ventrolateral preoptic region (VLPR) promotes sleep. During wakefulness, the ARAS inhibits the VLPR via activation of cholinergic neurons, monoaminergic cell bundles, and orexin nuclei in the lateral hypothalamus. The orexin system promotes wakefulness and alertness and works to balance sleep and wakefulness. Orexin system activation maintains the fully awake state for longer periods of time; conversely, deactivation of the orexin system allows for consolidated sleep during the night. Orexinergic signaling by 2 distinct forms, orexin A and orexin B, maintains wakefulness via continuous depolarization in wake-promoting brain nuclei. Sleep is cued by a homeostatic sleep drive inhibition of orexins. During sleep, the ventrolateral preoptic nucleus inhibits the ARAS via 2 inhibitory neurotransmitters, -aminobutyric acid (GABA) and galanin. GABA is the neurotransmitter that most widely promotes sleep, whereas norepinephrine and dopamine promote wakefulness; serotonin is necessary for both optimal sleep and wakefulness. Flip-flop switching also regulates the transition from non-REM to REM sleep.

• #1 Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01496-3

  Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in sleep in which the airways narrow or collapse during sleep, causing obstructive sleep apnea. The mechanism of upper airway collapse is incompletely understood but is associated with several factors, including obesity, craniofacial changes, altered muscle function in the upper airway, pharyngeal neuropathy, and fluid shifts to the neck. […] The pathophysiological mechanisms underlying OSAS are complex and multifactorial, and furthermore, the underlying causes of OSAS vary substantially between afflicted individuals, with many unknown and poorly understood aspects. With the increase in OSAS-related research, it is gradually recognized that there are anatomical factors and functional factors involved in the mechanism of upper airway collapse.

• #1 Sleep apnea – Wikipedia

  https://en.wikipedia.org/wiki/Sleep_apnea

  Sleep apnea may be categorized as obstructive sleep apnea (OSA), in which breathing is interrupted by a blockage of air flow, central sleep apnea (CSA), in which regular unconscious breath simply stops, or a combination of the two. […] OSA has four key contributors; these include a narrow, crowded, or collapsible upper airway, an ineffective pharyngeal dilator muscle function during sleep, airway narrowing during sleep, and unstable control of breathing (high loop gain). […] In CSA, the basic neurological controls for breathing rate malfunction and fail to give the signal to inhale, causing the individual to miss one or more cycles of breathing. […] When breathing is paused due to upper airway obstruction, carbon dioxide builds up in the bloodstream. […] The brain is signaled to awaken the person, which clears the airway and allows breathing to resume.

• #1 Central sleep apnea: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/central-sleep-apnea-pathogenesis

  Central apneas are periods of absent airflow due to lack of respiratory effort. They occur when inhibitory input to the respiratory center of the brain exceeds excitatory input, which may occur during sleep because sleep abolishes wakefulness-related excitatory input. Recurrent central apneas are the hallmark feature of central sleep apnea (CSA), which is a heterogeneous group of disorders with varying etiologies and pathophysiologic mechanisms. […] In this topic review, the pathogenesis of central sleep apnea is discussed. […] Apneic threshold — Respiration during non-rapid eye movement (NREM) sleep is critically dependent on chemical influences, especially arterial carbon dioxide tension (PaCO2). Central apnea results if arterial PaCO2 is lowered below a highly sensitive „apneic threshold”.

• #1 Sleep disorder – Wikipedia

  https://en.wikipedia.org/wiki/Sleep_disorder

  A sleep disorder, or somnipathy, is a medical disorder affecting an individual’s sleep patterns, sometimes impacting physical, mental, social, and emotional functioning. Sleep disorders are broadly classified into dyssomnias, parasomnias, circadian rhythm sleep disorders involving the timing of sleep, and other disorders, including those caused by medical or psychological conditions. […] A systematic review found that traumatic childhood experiences, such as family conflict or sexual trauma, significantly increase the risk of several sleep disorders in adulthood, including sleep apnea, narcolepsy, and insomnia. […] Neurodegenerative diseases are often associated with sleep disorders, particularly when characterized by the abnormal accumulation of alpha-synuclein, as seen in multiple system atrophy (MSA), Parkinson’s disease (PD), and Lewy body disease (LBD).

• #1 Sleep Disorders in Parkinson’s Disease: Clinical Features, Iron Metabolism and Related Mechanism | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082924

  To investigate clinical features, iron metabolism and neuroinflammation in Parkinsons disease (PD) patients with sleep disorders (SD). […] Depression, restless leg syndrome, autonomic disorders and fatigue are the important contributors for the poor sleep in PD patients. Abnormal iron metabolism may cause excessive iron deposition in brain and be related to SD in PD patients through dual potential mechanisms, including neuroinflammation by activating microglia and neurotoxicity by targeting neurons. […] Pathology and autopsy studies observed excessive iron deposition in substantia nigra, with total iron elevated by 25% to 100% and iron ions by 225%. […] Here, we found that iron level in CSF in PD-SD group was dramatically elevated compared with PD-NSD group, implying an excessive iron deposition in brain.

• #1 Sleep Disorders in Patients With Multiple Sclerosis

  https://practicalneurology.com/diseases-diagnoses/ms-immune-disorders/sleep-disorders-in-patients-with-multiple-sclerosis/30213/

  Identifying and treating sleep problems can help optimize the well-being and function of patients with multiple sclerosis. Despite our understanding that sleep disorders are more prevalent in and have significant impact on persons with multiple sclerosis (MS), sleep disorders often remain unaddressed in routine clinical evaluation of patients with MS. Some of the most commonly encountered, consequential, and yet treatable sleep disorders in patients with MS include chronic insomnia, sleep-disordered breathing (SDB), and restless legs syndrome (RLS). Enhanced understanding of potential causes, consequences, and presentations of common sleep problems may offer new opportunities to optimize function and quality of life for patients with MS. […] An important component of clinical management for patients with MS includes identifying treatable or reversible comorbid conditions that can contribute to and worsen these symptoms.

• #1 Ricardo Osorio, MD, on the Association Between Sleep-Wake Disruptions, Pathogenesis of Alzheimer

  https://www.neurologylive.com/view/ricardo-osorio-md-association-between-sleep-wake-disruptions-pathogenesis-of-alzheimer

  Emerging evidence suggests that sleep disruption results in higher levels of markers associated with Alzheimer disease. […] In the last 5-7 years we have new data that shows that sleep disruption is not only a consequence of Alzheimer, but its also a risk factor. […] The data reveals that sleep disruptions result in higher levels of markers associated with Alzheimer disease, increase CNS oxidative stress and disrupt clearance of Alzheimer-promoting A peptides. […] Osorio concludes that enhancing sleep can help in lowering the risk or reversing the signs of accelerated cognitive aging, Alzheimer disease or other neurodegenerative diseases and opens a new path of research to be explored.

• #1 Sleepwalking: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1188854-overview

  The parasomnias have been thought to represent not pathologic cerebral functioning but, rather, a response to central nervous system (CNS) activation that results in sleep-wake or rapid eye movement (REM)NREM state confusion, instability, or overlap. However, studies have demonstrated differences between sleep patterns and neuronal sleep control mechanisms in individuals who have parasomnias and corresponding patterns and mechanisms in individuals who do not. […] Sleepwalkers appear to have an abnormality in SWS regulation. The dissociation that occurs between body and mind sleep appears to arise from activation of thalamocingulate pathways with persisting deactivation of other thalamocortical arousal systems. The first SWS period of the night is considered to be more disturbed in somnambulistic individuals, and the entire NREM-REM sleep cycle is more fragmented. Because these disorders occur more frequently in children, these differences have been suggested as signs of CNS immaturity.

• #1

  https://link.springer.com/article/10.1007/s00421-024-05556-6

  Sleep disorders are prevalent among the general population and even more in individuals suffering from chronic diseases. Recent data reveal promising effects of physical exercise as a non-pharmacological approach for improving sleep and managing various sleep disorders. […] The role of exercise in preventing and improving sleep disorders is probably much higher than what is currently exploited. […] Regular exercise, including short-term aerobic activity, resistance training, and mind-body exercises, can effectively improve sleep quality, particularly in cases of insomnia and sleep-disordered breathing. […] Additionally, increasing evidence supports the effectiveness of aerobic and strength training, and body-mind exercises such as yoga in managing sleep-related movement disorders. […] More research is needed to define how exercise affects the physiology of sleep, and consequently how to use exercise in patients with sleep disorders.

• #1 Mechanism of Insomnia after Stroke Based on Intestinal Flora | IJGM

  https://www.dovepress.com/mechanism-of-insomnia-after-stroke-based-on-intestinal-flora-peer-reviewed-fulltext-article-IJGM

  Stroke has emerged as the second leading cause of mortality. Insomnia after stroke is a highly prevalent complication of stroke with a complex mechanism, impacting daily activities and hindering neurological function rehabilitation while also increasing the risk of stroke recurrence. […] Numerous studies have emphasized the crucial function of intestinal flora in the pathological changes associated with insomnia after stroke. It can influence sleep patterns following a stroke by modulating various pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, immune responses, and neural mechanisms. Disruption of intestinal flora can adversely affect post-stroke sleep quality, while sleep after stroke can also lead to intestinal flora imbalance. […] The etiology of post-stroke insomnia remains unclear and is believed to be associated with local brain damage, neurological dysfunction, psychological factors, gender, and other related factors. Recent studies have indicated that the majority of anatomical components involved in regulating sleep mechanisms are situated in the hypothalamus and brain stem. Damage to these areas may disrupt the sleep-wake cycle system, potentially leading to post-stroke insomnia.

• #1 Circadian clock dysregulation: a potential mechanism of depression in obstructive sleep apnea patients | Translational Psychiatry

  https://www.nature.com/articles/s41398-024-03134-0

  Obstructive sleep apnea (OSA) is characterized by co-occurrence with affective disorders. Our study aims to investigate the association of circadian clock gene expressions, and the presence and severity of depressive symptoms in OSA patients. […] Dysregulated circadian clock gene expression in OSA patients is linked to depressive symptom severity, suggesting circadian disruption may underlie affective symptoms in OSA. […] The dysregulation of circadian gene expression in OSA has garnered significant attention in recent discussions, particularly in relation to the role of nocturnal intermittent hypoxia and the potential impact of disrupted circadian rhythms in OSA. […] Our results suggest that disruption of circadian clock gene expression in OSA correlates with depressive symptoms. […] The dysregulation in circadian rhythmicity, as well as sleep fragmentation in OSA, may lead to more liable chronotype and sleep disruption which could be a possible cause of affective disorders in OSA, however, the interaction is likely to be bidirectional and it is hard to establish a basis for unidirectional cause and effect relationship.

• #1

  https://www.healthxchange.sg/news/sleep-disorders-sufferers-may-have-help-from-mechanism-regulating-biological-clock

  Mutations in a specific protein (called casein kinase 1) alters the core clock protein (called PERIOD or PER), and this changes the timing of the biological clock. A study by scientists from Duke-NUS Medical School (Duke-NUS) and the University of Tokyo provide new evidence which supports the presence of a key mechanism that regulates our biological clock. […] In the study published in PNAS, the team used preclinical models to validate that mutations in PER2 protein can alter the balance of the circadian period, which can lead to sleep disorders. This helps us understand and validate the genetic and biochemical regulation of our circadian sleep/wake cycles, which can produce a morning lark or night owl effect. Understanding how the clock works can help in the development of new therapeutic interventions for treating people with sleep disorders.

• #1 How sleep deprivation can cause inflammation – Harvard Health

  https://www.health.harvard.edu/healthbeat/how-sleep-deprivation-can-cause-inflammation

  Sleep deprivation is a condition that occurs when you don’t get enough sleep, or enough good quality sleep. […] Research has found that sleep deprivation is associated with markers of inflammation, such as increases in inflammatory molecules including cytokines, interleukin-6, C-reactive protein (a marker of inflammation that’s elevated in people at risk for heart disease and diabetes), and others. […] The association between sleep deprivation and inflammation markers could help explain why people who sleep poorly are at risk for cardiovascular disease, high blood pressure, and diabetes, among other chronic conditions. […] How does a lack of sleep contribute to inflammation? One theory focuses on blood vessels. During sleep, blood pressure drops and blood vessels relax. When sleep is restricted, blood pressure doesn’t decline as it should, which could trigger cells in blood vessel walls that activate inflammation.

• #1 Study points to a universal immune mechanism as a regulator of sleep | ScienceDaily

  https://www.sciencedaily.com/releases/2017/02/170202141838.htm

  Sleep may be regulated in part by several brain-based immune proteins collectively called inflammasome NLRP3, suggests new research conducted in mice. […] The researchers say the inflammasome — which works by unleashing a cascade of immune molecules in response to inflammation and infection — emerges as a central promoter of sleep following such events. […] Scientists have known for a while that certain immune molecules enhance sleep and are activated by infection, but this is the first study suggesting a common underlying mechanism that regulates sleep and plays a critical role in recuperative sleep responses. […] Results of the study show that the inflammasome recruits a sleep-inducing molecule to trigger somnolence following sleep deprivation and exposure to a bacterial toxin. […] „Our research points, for the first time, to the inflammasome acting as a universal sensing mechanism that regulates sleep through the release of immune molecules,” said study senior investigator Mark R. Zielinski, instructor in psychiatry at HMS.

• #1 Exploring the bidirectional relationship between sleep disorders and atrial fibrillation: implications for risk stratification and management | The Egyptian Heart Journal | Full Text

  https://tehj.springeropen.com/articles/10.1186/s43044-024-00524-z

  Atrial fibrillation (AF) is characterized by the absence of p-waves on ECG and irregular rhythm. […] Concurrently, sleep disorders such as obstructive sleep apnea (OSA), insomnia, narcolepsy, and circadian rhythm disorders which are a group of conditions associated with the bodys internal clock that affect the timing of sleep and alertness, are raising concerns due to their potential associations to arrhythmias. […] Various meta-analysis cohorts have highlighted a strong connection between sleep disorders and atrial fibrillation (AF). Patients with sleep disorders, especially OSA, have a higher likelihood of developing AF, and conversely, those with AF are more prone to sleep disorders. […] Sleep disorders may play an important role in atrial remodeling as well as electrophysiological abnormalities, rendering the atrial tissue more susceptible to arrhythmogenesis.

• #1 Fragmented Nocturnal Sleep May Play Role in Pathogenesis of MASLD – Neurology Advisor

  https://www.neurologyadvisor.com/news/fragmented-nocturnal-sleep-pathogenesis-masld/

  Compared with healthy individuals, patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have longer nocturnal wakefulness, more fragmented sleep, and lower sleep efficiency, according to study findings published in Frontiers in Network Physiology. […] Further studies applying objective methods combined with subsequent interventions, such as repetitive sleep counseling sessions or melatonin supplementation, are warranted to evaluate the therapeutic potential of improving sleep efficiency in treating MASLD. […] Although there were no significant differences in bedtime, sleep latency, and sleep duration (P .05) between the groups, actigraphy data revealed the MASLD vs control group had more night awakenings (median, 8.5 vs 5.5; P =.0036) and more prolonged WASO (median, 45.4 vs 21.3 mins; P =.004), as well as lower sleep efficiency (86.5% vs 92.8%; P =.0008).

• #1

  https://aesnet.org/abstractslisting/sleep-disturbances-as-a-potential-mechanism-of-post-traumatic-epileptogenesis

  Sleep disturbances are common and persistent symptoms after traumatic brain injury, which can significantly complicate recovery. […] However, the relationship between sleep disturbances following brain trauma and development of post-traumatic epilepsy remains poorly understood. […] Sleep duration in CCI-injured animals was significantly decreased (sham = 13.8 0.2 vs. CCI = 12.4 0.3 hours, p 0.01) up to 5 months post-injury. In addition, CCI-injured animals had significantly fragmented sleep, which was frequently interrupted by brief in duration awake periods (sham = 2.6 0.2 vs. CCI = 4.9 0.4 times/NREM1, p 0.001). Also, CCI-injured animals had a significant increase in delta oscillation (0.5-4 Hz) detected on ipsilateral (sham = 11 2 vs. CCI = 18 01 %, p 0.01) and contralateral (sham = 12 2 vs. CCI = 18 1 %, p 0.01) ECoG screws up to 5 months post-CCI.

• #2 Sleep Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560720/

  Sleep disorders encompass several clinical problems encountered in outpatient settings. Sleep disorders have a broad differential diagnosis; therefore, standardized definitions and classifications are essential. There are many different types of sleep disorders. Using the International Classification of Sleep Disorders (ICSD) helps in providing a standardized classification and definitions for sleep disorders. Sleep disorders are common in both adults and children. However, children with sleep disorders may present with different symptoms than adults. […] Sleep disorders are a group of conditions that disturb normal sleep patterns. Sleep disorders are one of the most common clinical problems encountered. Inadequate or non-restorative sleep can interfere with normal physical, mental, social, and emotional functioning. Sleep disorders can affect overall health, safety, and quality of life.

• #2 Insomnia Overview: Epidemiology, Pathophysiology, Diagnosis and Monitoring, and Nonpharmacologic Therapy

  https://www.ajmc.com/view/insomnia-overview-epidemiology-pathophysiology-diagnosis-and-monitoring-and-nonpharmacologic-therapy

  This model of the sleep-wake cycle is often called the flip-flop switch because it permits one to either be awake or asleep, but not both, at the same time. Via the switching mechanism, the active state suppresses the other state until circadian rhythms induce a switch to the reciprocal state. The cerebral cortex and the limbic system further modify wakefulness. Sleep-promoting centers in the anterior hypothalamus project into the brainstem and posterior arousal centers and function with the lateral hypothalamus as a sleep-wake switch. […] Circadian factors promote wakefulness on a roughly 24-hour biological clock, whereas homeostatic factors respond to accumulated wakefulness with the drive for sleep. In the brain, the ARAS promotes wakefulness and the ventrolateral preoptic region (VLPR) promotes sleep. During wakefulness, the ARAS inhibits the VLPR via activation of cholinergic neurons, monoaminergic cell bundles, and orexin nuclei in the lateral hypothalamus. The orexin system promotes wakefulness and alertness and works to balance sleep and wakefulness. Orexin system activation maintains the fully awake state for longer periods of time; conversely, deactivation of the orexin system allows for consolidated sleep during the night. Orexinergic signaling by 2 distinct forms, orexin A and orexin B, maintains wakefulness via continuous depolarization in wake-promoting brain nuclei. Sleep is cued by a homeostatic sleep drive inhibition of orexins. During sleep, the ventrolateral preoptic nucleus inhibits the ARAS via 2 inhibitory neurotransmitters, -aminobutyric acid (GABA) and galanin. GABA is the neurotransmitter that most widely promotes sleep, whereas norepinephrine and dopamine promote wakefulness; serotonin is necessary for both optimal sleep and wakefulness. Flip-flop switching also regulates the transition from non-REM to REM sleep.

• #2 Sleep Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560720/

  There are different causes for different sleep disorders. For each sleep disorder listed below, more details are discussed in the pertinent section referenced below. […] The exact causes of insomnia are unknown. Some contributing factors include environmental, genetic, psychological, and behavioral, leading to hyperarousal. […] The causes of SDB range from breathing control to upper airway and chest wall mechanics, causing compromised ventilatory and resistive loading. SDB is a spectrum of disorders ranging from syndrome to OSA and central sleep apnea (CSA). In the obstructive type of SDB, obesity plays a key role, and more information is discussed in the sections on OSA, CSA, and obesity hypoventilation syndrome. […] The central causes of hypersomnolence are commonly due to intrinsic abnormalities in the central nervous system’s control of sleep-wake. Central hypersomnia is usually divided into three main subtypes: narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia (IH), which are reviewed in more detail in separate sections.

• #2 Sleep disorders in end-stage kidney disease – UpToDate

  https://www.uptodate.com/contents/sleep-disorders-in-end-stage-kidney-disease

  Pathogenesis — Contributors to insomnia include restless leg syndrome (RLS); periodic limb movement (PLM); sleep apnea; metabolic factors, including uremia, anemia, hypercalcemia, bone pain, and pruritus; anxiety and depression; circadian rhythm disorders, such as delayed-sleep phase syndrome; the use of medications that prevent sleep; and poor sleep hygiene, including frequent napping during daytime dialysis. […] Elevated plasma levels of orexin (a neuropeptide that promotes wakefulness) and systemic inflammation may also contribute to poor sleep among patients with ESKD. The diurnal rhythm of melatonin is disturbed in patients with ESKD, and it is also related to the degree of kidney dysfunction in patients with chronic kidney disease (CKD). Some studies have suggested that the timing of the dialysis shift alters the severity of insomnia such that insomnia is worse among patients who are dialyzed in the morning, but this has not been shown in all studies.

• #2 Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01496-3

  Various pathophysiological factors interact to contribute to the pathogenesis of OSAS. […] The reduction in upper airway volume caused by obesity or craniofacial structural abnormalities and soft tissue changes is an important factor in upper airway collapse. […] Upper airway anatomical abnormalities are a key factor in the pathogenesis of OSAS. […] Enlargement of soft-tissue structures in and around the airways is an important cause of pharyngeal airway narrowing in most cases of OSAS. […] Fluid retention may contribute to the pathogenesis of OSAS, and nocturnal rostral fluid shift refers to the nighttime redistribution of fluid accumulated in the legs to the upper parts of the body while lying in bed. […] Although upper airway obstruction may be due to a variety of factors, such as obesity, there is increasing evidence that individual collapsibility is also a key factor in upper airway obstruction.

• #2 Sleep apnea – Wikipedia

  https://en.wikipedia.org/wiki/Sleep_apnea

  This carbon dioxide build-up may be due to the decrease of output of the brainstem regulating the chest wall or pharyngeal muscles, which causes the pharynx to collapse. […] As a result, people with sleep apnea experience reduced or no slow-wave sleep and spend less time in REM sleep. […] There are two main mechanisms that drive the disease process of CSA, sleep-related hypoventilation and post-hyperventilation hypocapnia. […] The most common cause of CSA is post-hyperventilation hypocapnia secondary to heart failure. […] This occurs because of brief failures of the ventilatory control system but normal alveolar ventilation. […] In contrast, sleep-related hypoventilation occurs when there is a malfunction of the brain’s drive to breathe. […] The underlying cause of the loss of the wakefulness drive to breathe encompasses a broad set of diseases from strokes to severe kyphoscoliosis.

• #2 Central sleep apnea: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/central-sleep-apnea-pathogenesis

  In patients who manifest central apneas, prolonged hyperventilation, prolonged hypoxia, or concomitant inhibitory factors offset the effects of STP and allow central apnea to occur when the PaCO2 is reduced below the apneic threshold. […] Central apnea occurs in cycles of apnea or hypopnea, alternating with hyperpnea.

• #2 Sleep Disorders in Patients With Multiple Sclerosis

  https://practicalneurology.com/diseases-diagnoses/ms-immune-disorders/sleep-disorders-in-patients-with-multiple-sclerosis/30213/

  Although the primary mechanism(s) underlying MS-related fatigue have yet to be fully elucidated, several treatable comorbidities including sleep disorders and disturbances are recognized as important secondary causes of fatigue in MS. Recent studies suggest that insomnia, obstructive sleep apnea (OSA), and RLS in particular are independent predictors of fatigue in patients with MS, and that successful treatment of these conditions may improve fatigue. […] Sleep disturbances are also associated with mood disorders among persons with MS. […] Interestingly, an emerging body of evidence has linked sleep disturbances to cognitive dysfunction in MS, although measures of sleep and cognition across studies have been variable. […] Although larger population-based studies are still needed, current research suggests a higher prevalence of OSA in patients with MS compared to the general population.

• #2 Sleep disorder – Wikipedia

  https://en.wikipedia.org/wiki/Sleep_disorder

  Sleep disturbances have also been observed in Alzheimer’s disease (AD), affecting about 45% of its population. […] One factor that could explain this change in sleep architecture is a disruption in the circadian rhythm, which regulates sleep. […] It has been shown that the sleep-wake cycle influences the beta-amyloid burden, a central component found in Alzheimer’s disease (AD). […] The decrease in the quantity and quality of NREM SWS, along with sleep disturbances, will therefore increase the AB plaques. […] Although the causal relationship is unclear, the development of AD correlates with the onset of prominent sleep disorders. […] Recent studies have also linked sleep disturbances, neurogenesis, and AD. […] Changes in sleep architecture in patients with AD occur during the preclinical phase of the disease.

• #2 The Genetic Landscape of Sleep Disorders in Parkinson’s Disease

  https://www.mdpi.com/2075-4418/14/1/106

  RBD is a sleep disorder characterized by abnormal motor behavior associated with dream mentation and loss of atonia during REM sleep. Scientific attention over RBD has increased due to its association with α-synucleinopathies. More specifically, there is accumulating evidence that the idiopathic/isolated form of RBD (IRBD) constitutes the prodromal stage of the α-synucleinopathies, as most of these cases are eventually diagnosed with PD or dementia with Lewy bodies (DLB), with an estimated rate of conversion of 34% after five years from the IRBD diagnosis, 74% after ten and 91% after fourteen years. […] The fact that the severity of the GBA mutation would correspond to the PD phenotype was also addressed in the study of Thaler et al. A total of 355 PD patients were included in this study; 152 iPD patients, 139 mild GBA (mGBA) mutation carriers, 48 severe GBA (sGBA) mutation carriers and 16 patients with GD and PD (GD-PD). Both sGBA and GD-PD had higher frequencies of RBD and hallucinations compared to the other groups of patients.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Types-of-sleep-disorders.aspx

  This type of disorder occurs when there is complete or partial obstruction of the upper airway. This may be of varying severity ranging from snoring to severe obstruction and arousal from sleep. […] Narcolepsy occurs in young adults in their second to third decades of life. It affects men and women equally. There is excessive daytime sleepiness, paralysis of the muscles during sleep, hallucinations during sleep and cataplexy (abnormal movements, emotional changes etc.). […] These are problems that are associated with timing of sleep and wakefulness. The human body has its own clock called the circadian rhythm. This resides in the suprachiasmatic nucleus (SCN). This clock regulates the sleep and wake rhythms of the body.

• #2 Circadian clock dysregulation: a potential mechanism of depression in obstructive sleep apnea patients | Translational Psychiatry

  https://www.nature.com/articles/s41398-024-03134-0

  Our results may suggest that dysregulated expression of circadian clock genes and overall disruption of circadian rhythmicity in OSA may be a possible pathomechanism underlying the close connection between OSA and affective disorders. […] The overnight disruption of circadian gene expression, observed in our study, may be mediated by nocturnal intermittent hypoxia (IH). […] Studies with OSA patients provide evidence that HIF-1 as an oxygen-sensitive transcription factor contributes to the regulation of circadian rhythms. […] The findings of this study hold important implications for both clinical practice and future research. […] OSA patients have dysregulated expression of circadian clock genes that are associated with the severity of depressive symptoms.

• #2 How sleep deprivation can cause inflammation – Harvard Health

  https://www.health.harvard.edu/healthbeat/how-sleep-deprivation-can-cause-inflammation

  A lack of sleep might also alter the body’s stress response system. […] In addition, a sleep shortfall interferes with the normal function of the brain’s housecleaning system, termed the glymphatic system (not to be confused with the lymphatic system in the rest of the body). […] Without a good night’s sleep, this housecleaning process is less thorough, allowing the protein to accumulate and inflammation to develop. […] Just one night of lost sleep can keep beta-amyloid levels higher than usual. […] The problem is not so much a single night’s poor sleep, which you can compensate for, but a cumulative pattern of sleep loss, leading to decreases in the structural integrity, size, and function of brain regions like the thalamus and hippocampus, which are especially vulnerable to damage during the early stages of Alzheimer’s disease.

• #2 Study points to a universal immune mechanism as a regulator of sleep | ScienceDaily

  https://www.sciencedaily.com/releases/2017/02/170202141838.htm

  Although warranting further study, the observations suggest that the inflammasome, the constellation of sleep-regulating proteins, may play an evolutionary role as a guardian of brain health and vitality that wards off the effects of sleep deprivation and infection. […] „We already know that sleep plays a protective role in resolving infections so our observation of inflammasome activation following infection suggests this immune mechanism may have a brain-protective role,” Zielinski said. […] In a series of experiments, the scientists demonstrated that following sleep deprivation or exposure to bacteria, the inflammasome activates an inflammatory molecule called interleukin-1 beta, known to induce sleep and promote sleep intensity. […] Mice lacking the inflammasome gene had abnormal sleep responses following sleep deprivation.

• #2 Exploring the bidirectional relationship between sleep disorders and atrial fibrillation: implications for risk stratification and management | The Egyptian Heart Journal | Full Text

  https://tehj.springeropen.com/articles/10.1186/s43044-024-00524-z

  The detrimental impact of sleep disorders on atrial remodeling and electrophysiological abnormalities underscores the significance of their diagnosis and treatment. […] The connection between sleep disturbances and AF involves multifaceted pathophysiological mechanisms. […] One such is the autonomic dysregulation caused by sleep disorders and how it plays a huge role in the pathogenesis of AF. […] In OSA, recurrent episodes of upper airway collapse cause intermittent hypoxia and hypercapnia, thereby stimulating a hypoxic stress response by the sympathetic nervous system. […] This response leads to sympathetic over-activity which persists during brief arousals from sleep, contributing to tachycardia and increased blood pressure. […] The repetitive apneic episodes are triggers of oxidative stress and inflammation, which can in turn cause endothelial dysfunction that leads to atrial remodeling and subsequent changes favoring AF substrate formation.

• #2 Sleep Disturbances as a Potential Mechanism of Post-Traumatic Epileptogenesis | ViP Leadership Award | Perelman School of Medicine at the University of Pennsylvania

  https://www.med.upenn.edu/PTERC/sleep-disturbances-as-a-potential-mechanism-of-post-traumatic-epileptogenesis

  These preliminary results, together with histopathological changes observed in the SCN, led to our central hypothesis that network oscillatory disruptions in the circadian rhythm center lead to disrupted sleep states over time post-injury. […] Our objectives in this proposal are to identify the extent of interneuron-related dysfunction and pathology in the SCN that may lead to the development of sleep-wake disturbances observed over time post-CCI injury. […] In this way, we will use our unique, large animal model of PTE (swine), along with in vivo electrophysiology, continuous home cage video monitoring, and histopathology, to identify the extent to which pathological changes in the SCN interneurons disrupt normal sleep during post-traumatic epileptogenesis. […] Examination of the circuit level changes in a clinically relevant large animal model of PTE, in parallel with neuropathological outcome, provides a powerful translational approach to understanding disturbances in normal sleep and circadian rhythms during development of PTE.

• #3 Insomnia Overview: Epidemiology, Pathophysiology, Diagnosis and Monitoring, and Nonpharmacologic Therapy

  https://www.ajmc.com/view/insomnia-overview-epidemiology-pathophysiology-diagnosis-and-monitoring-and-nonpharmacologic-therapy

  The 3P behavioral model of insomnia helps to explain how acute insomnia becomes chronic and lays the groundwork for assessing insomnia in individual patients. The 3Ps, which occur in temporal order, are factors that: Predispose an individual to insomnia, Precipitate an acute episode of insomnia, Perpetuate insomnia from acute to chronic. Predisposing factors, which are generally not modifiable, include genetics and personality traits (eg, being a worrier; family history of poor sleep) that lead to physiologic and cognitive hyperarousal. Precipitating factors that trigger insomnia are typically stressful life events. Perpetuating factors are the maladaptive behaviors, thoughts, and coping strategies that allow insomnia to continue after original triggers have resolved. Physical examples of maladaptive behaviors include daytime napping or spending too much time in bed. Less quantifiable perpetuators include dysfunctional beliefs, expectations, and attributions about sleep as well as an intense desire to solve the sleep problem.

• #3 Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01496-3

  In recent years, a number of studies have shown that a low respiratory arousal threshold may be an important endotype of OSAS. […] In ventilatory control, loop gain is a measure of respiratory instability, which refers to unstable ventilatory chemoreflex control and is recognized as a key pathophysiological feature that contributes to OSAS. […] Increased pharyngeal dilator muscle activity in OSAS patients compared with matched controls has been interpreted as evidence of a neuromuscular protective compensatory reflex in response to anatomical compromise in OSAS. […] Central sleep apnea (CSA) is a sleep-breathing disorder characterized by apnea and hypopnea caused by a lack of drive to breathe during sleep. […] The occurrence of respiratory events can be intermittent or periodic, and patients could also experience obstructive respiratory events. […] The pathophysiological mechanism of OSAS and the relationship between the alterations in potential signaling pathways and multiple systemic diseases are described in detail and comprehensively, and the corresponding therapeutic strategies for different pathogeneses are discussed.

• #3 Sleep disturbance in movement disorders: insights, treatments and challenges | Journal of Neurology, Neurosurgery & Psychiatry

  https://jnnp.bmj.com/content/92/7/723

  The rate, nature and temporal pattern of these sleep disturbances vary across the different movement disorders. […] For example, in Parkinsons disease (PD) the rate of sleep disorders has been estimated to be as high as 98%, with rapid eye movement (REM) sleep behaviour disorder well established as predating motor symptom onset. […] This review provides an overview of the common sleep disorders and the evidence to date for the patterns and prevalence across a spectrum of movement disorders. […] We discuss the tools available for sleep assessment, the impact of medication used in motor symptom management on sleep, and how disturbed sleep can affect daytime motor function. […] Several studies have also reported reduced melatonin secretion in patients, with a casecontrol study showing a fourfold decrease in circulating melatonin levels in those with PD, and reduced melatonin rhythm amplitude in those with excessive daytime sleepiness.

• #3 Sleep Disorders in Patients With Multiple Sclerosis

  https://practicalneurology.com/diseases-diagnoses/ms-immune-disorders/sleep-disorders-in-patients-with-multiple-sclerosis/30213/

  The reason for this association is still unknown. […] There is a link between brainstem lesion burden and both obstructive and central sleep apnea in patients with MS, and progressive MS is associated with increased apnea severity, controlling for age and body mass index. […] Although prevalence of SDB in persons with MS seems higher than in the general population, OSA appears underrecognized. […] The majority of studies suggest that RLS is 3 times more prevalent in patients with MS than in the general population. […] Although reasons for increased prevalence are speculative, there is a proposed role for dysfunction of downstream dopaminergic pathways that project to the spinal cord, are responsible for the suppression of sensory inputs and motor excitability and are susceptible to damage from diseases that affect the spinal cord.

• #3 Mechanism of Insomnia after Stroke Based on Intestinal Flora | IJGM

  https://www.dovepress.com/mechanism-of-insomnia-after-stroke-based-on-intestinal-flora-peer-reviewed-fulltext-article-IJGM

  After experiencing a stroke, there is an excessive activation of the HPA axis, leading to impaired negative feedback mechanisms and an inability to maintain balance. This results in excessive production and accumulation of cortisol. […] The interaction between intestinal flora and the HPA axis is significant. Changes in intestinal microorganisms can impact the HPA axis by modifying neurotransmitter-related neuro-endocrine signaling pathways or inflammatory response. Conversely, activation of the HPA axis can affect gastrointestinal function, leading to alterations to the composition of intestinal flora. […] The gastrointestinal tract is the most densely populated gathering place of immune cells in the human body and serves as the largest immune organ. The diversity of intestinal flora directly impacts the stability of immune function, with the establishment and maintenance of intestinal flora homeostasis playing a crucial role in shaping, developing, and regulating the immune system.

• #3 Sleep Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560720/

  The responsible causes of CRSD can be divided into two major groups (1): the environment is not well aligned with the internal circadian timing (e.g., shift work, jetlag); and (2) those occurring when the circadian timing system becomes altered relative to the external environment (e.g., delayed sleep phase syndrome, non-24, advanced sleep phase syndrome, irregular sleep-wake rhythm). […] The causes of parasomnia vary from environmental, genetic, and gene-environment interactions, all of which may play a significant role in the origin of parasomnias. […] Abnormal movements during sleep are disorders of motor control excitation or disinhibition often associated with sleep disturbances. The etiology of various movements condition during sleep depends on the type of that disorder. For example, in restless legs syndrome (RLS), the etiology could be primarily due to familial and genetic predisposition or secondary to iron deficiency.

• #4 Mechanism of Insomnia after Stroke Based on Intestinal Flora | IJGM

  https://www.dovepress.com/mechanism-of-insomnia-after-stroke-based-on-intestinal-flora-peer-reviewed-fulltext-article-IJGM

  Intestinal flora can impact sleep through immune and inflammatory pathways. Conversely, insomnia can affect intestinal flora through immune responses and inflammatory pathways caused by microglia. This may result in a vicious cycle effect. […] The intestinal flora plays an essential role as the primary producer of numerous neurotransmitters, with over 90% of brain neurotransmitters being primarily synthesized in the human intestine. The gut microbiota interacts with the nervous system by influencing various neurotransmitters and plays a role in the regulation of sleep. […] Insomnia is associated with the levels of 5-HT, GABA, DA, NE, melatonin (MT), and other neurotransmitters. […] The relationship between intestinal flora and post-stroke insomnia is closely intertwined. Intestinal flora can impact the onset and progression of post-stroke insomnia by influencing the HPA axis, immune pathways, neural pathways, and other mechanisms. The imbalance of intestinal flora, stroke, and insomnia interact in a manner that easily perpetuates a vicious cycle.

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