scholarly journals 0141 A Novel, Orally Available Orexin 2 Receptor-Selective Agonist, TAK-994, Shows Wake-Promoting Effects Following Chronic Dosing in an Orexin-Deficient Narcolepsy Mouse Model

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A56-A56
Author(s):  
T Ishikawa ◽  
M Suzuki ◽  
H Kimura
Keyword(s):  
Treatment Group ◽  
Mouse Model ◽  
Eye Movement ◽  
Rem Sleep ◽  
Day Treatment ◽  
Nrem Sleep ◽  
Sleep Time ◽  
Control Group ◽  
Sleep Phase ◽  
Selective Agonist

Abstract Introduction The use of an orexin 2 receptor (OX2R) agonist may be a promising approach for the treatment of narcolepsy type 1. TAK-994 is a novel, orally available OX2R-selective agonist with >700-fold selectivity against orexin 1 receptor. Single administration of TAK-994 ameliorates narcolepsy-like symptoms such as fragmentation of wakefulness and cataplexy-like episodes in orexin/ataxin-3 mice, a narcolepsy mouse model with orexin deficiency. In this study, we evaluated the effect of chronic dosing with TAK-994 on sleep/wakefulness states in orexin/ataxin-3 mice. Methods Orexin/ataxin-3 mice were grouped into two cohorts: a control group and a 14-day treatment group. In the control group, vehicle was administered orally to mice three times a day: zeitgeber time 12 (ZT12), ZT15 and ZT18, for 14 days. In the 14-day treatment group, TAK-994 was administered orally to mice at ZT12, ZT15 and ZT18 for 14 days. Electroencephalogram/electromyogram analysis was performed on day 1 and day 14 (ZT12-ZT21), and the subsequent sleep phase (ZT0-ZT10). Results On day 1, TAK-994 significantly increased wakefulness time, accompanied by a decrease in non-rapid eye movement (NREM) sleep time and rapid eye movement (REM) sleep time, in orexin/ataxin-3 mice compared with the control group. On day 14, TAK-994 also significantly increased wakefulness time, and decreased NREM sleep time and REM sleep time in orexin/ataxin-3 mice. There were no changes in the time spent in wakefulness, NREM sleep and REM sleep during the subsequent sleep phase after chronic dosing with TAK-994. Conclusion Wake-promoting effects of TAK-994 were observed following chronic dosing for up to 14 days in orexin/ataxin-3 mice with no rebound of sleep. Overall, there was no clear difference in efficacy between the single and repeated administration of TAK-994 in orexin/ataxin-3 mice. Support This work was conducted by Takeda Pharmaceutical Company Limited.

scholarly journals The European starling (Sturnus vulgaris) shows signs of NREM sleep homeostasis but has very little REM sleep and no REM sleep homeostasis

SLEEP ◽  
2019 ◽  
Vol 43 (6) ◽  
Author(s):  
Sjoerd J van Hasselt ◽  
Maria Rusche ◽  
Alexei L Vyssotski ◽  
Simon Verhulst ◽  
Niels C Rattenborg ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Eye Movement ◽  
Rem Sleep ◽  
Spectral Power ◽  
Nrem Sleep ◽  
Sleep Time ◽  
European Starling ◽  
Dark Phase ◽  
Rapid Eye Movement ◽  
Sleep Homeostasis

Abstract Most of our knowledge about the regulation and function of sleep is based on studies in a restricted number of mammalian species, particularly nocturnal rodents. Hence, there is still much to learn from comparative studies in other species. Birds are interesting because they appear to share key aspects of sleep with mammals, including the presence of two different forms of sleep, i.e. non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. We examined sleep architecture and sleep homeostasis in the European starling, using miniature dataloggers for electroencephalogram (EEG) recordings. Under controlled laboratory conditions with a 12:12 h light–dark cycle, the birds displayed a pronounced daily rhythm in sleep and wakefulness with most sleep occurring during the dark phase. Sleep mainly consisted of NREM sleep. In fact, the amount of REM sleep added up to only 1~2% of total sleep time. Animals were subjected to 4 or 8 h sleep deprivation to assess sleep homeostatic responses. Sleep deprivation induced changes in subsequent NREM sleep EEG spectral qualities for several hours, with increased spectral power from 1.17 Hz up to at least 25 Hz. In contrast, power below 1.17 Hz was decreased after sleep deprivation. Sleep deprivation also resulted in a small compensatory increase in NREM sleep time the next day. Changes in EEG spectral power and sleep time were largely similar after 4 and 8 h sleep deprivation. REM sleep was not noticeably compensated after sleep deprivation. In conclusion, starlings display signs of NREM sleep homeostasis but the results do not support the notion of important REM sleep functions.

scholarly journals Sound disrupts sleep-associated brain oscillations in rodents according to its meaning

2021 ◽  
Author(s):  
Philipp van Kronenberg ◽  
Linus Milinski ◽  
Zoë Kruschke ◽  
Livia de Hoz
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Sensory Gating ◽  
Nrem Sleep ◽  
Brain Oscillations ◽  
Sleep Phase ◽  
Fast Decrease ◽  
Per Se ◽  
Eeg Power ◽  
Danger Detection

SummarySleep is essential but poses a risk to the animal. Filtering acoustic information according to its relevance, a process generally known as sensory gating, is crucial during sleep to ensure a balance between rest and danger detection. The mechanisms of this sensory gating and its specificity are not understood. Here, we tested the effect that sounds of different meaning had on sleep-associated ongoing oscillations. We recorded EEG and EMG from mice during rapid-eye movement (REM) and non-REM (NREM) sleep while presenting sounds with or without behavioural relevance. We found that sound presentation per se, in the form of an unfamiliar neutral sound, elicited a weak or no change in the sleep-dependent EEG power during NREM and REM sleep. In contrast, the presentation of a sound previously conditioned in an aversive task, elicited a clear and fast decrease in the sleep-dependent EEG power during both sleep phases, suggesting a transition to lighter sleep without awakening. The observed changes generally weakened over training days and were not present in animals that failed to learn. Interestingly, the effect could be generalized to unfamiliar neutral sounds if presented following conditioned training, an effect that depended on sleep phase and sound type. The data demonstrate that sounds are differentially gated during sleep depending on their meaning and that this process is reflected in disruption of sleep-associated brain oscillations without an effect on behavioural arousal.

scholarly journals The maturational trajectories of NREM and REM sleep durations differ across adolescence on both school-night and extended sleep

2012 ◽  
Vol 302 (5) ◽  
pp. R533-R540 ◽  
Author(s):  
Irwin Feinberg ◽  
Nicole M. Davis ◽  
Evan de Bie ◽  
Kevin J. Grimm ◽  
Ian G. Campbell
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Brain Activity ◽  
Physiological Role ◽  
Nrem Sleep ◽  
Sleep Time ◽  
Rapid Eye Movement ◽  
Time In Bed ◽  
Ultimate Explanation ◽  
Brain Changes

We recorded sleep electroencephalogram longitudinally across ages 9–18 yr in subjects sleeping at home. Recordings were made twice yearly on 4 consecutive nights: 2 nights with the subjects maintaining their ongoing school-night schedules, and 2 nights with time in bed extended to 12 h. As expected, school-night total sleep time declined with age. This decline was entirely produced by decreasing non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep durations increased slightly but significantly. NREM and REM sleep durations also exhibited different age trajectories when sleep was extended. Both durations exceeded those on school-night schedules. However, the elevated NREM duration did not change with age, whereas REM durations increased significantly. We interpret the adolescent decline in school-night NREM duration in relation to our hypothesis that NREM sleep reverses changes produced in plastic brain systems during waking. The “substrate” produced during waking declines across adolescence, because synaptic elimination decreases the intensity (metabolic rate) of waking brain activity. Declining substrate reduces both NREM intensity (i.e., delta power) and NREM duration. The absence of a decline in REM sleep duration on school-night sleep and its age-dependent increase in extended sleep pose new challenges to understanding its physiological role. Whatever their ultimate explanation, these robust findings demonstrate that the two physiological states of human sleep respond differently to the maturational brain changes of adolescence. Understanding these differences should shed new light on both brain development and the functions of sleep.

Effect of a Reversible Monoamine Oxidase-A Inhibitor (Moclobemide) on Sleep of Depressed Patients

1989 ◽  
Vol 155 (S6) ◽  
pp. 61-65 ◽  
Author(s):  
J. M. Monti
Keyword(s):  
Monoamine Oxidase ◽  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Sleep Time ◽  
Monoamine Oxidase A ◽  
Therapeutic Trial ◽  
Rapid Eye Movement ◽  
Symptoms Of Depression ◽  
Depressed Patients

The effect of moclobemide, a short-acting, reversible, preferential monoamine oxidase-A inhibitor in a 4-week therapeutic trial, on the sleep of ten depressed patients, was assessed by polysomnographic recordings. Compared with their time on placebo, patients receiving moclobemide showed improved sleep continuity, particularly during the intermediate and late stages of drug administration. The total increase in sleep time was comprised of larger amounts of stage 2 non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Withdrawal of moclobemide was followed by a further increase of REM sleep, although values did not surpass those sometimes observed in adults with normal sleep. In these patients, the symptoms of depression were rated as being significantly improved during the study period.

Heterogeneous activity level of jaw-closing and -opening muscles and its association with arousal levels during sleep in the guinea pig

2010 ◽  
Vol 298 (1) ◽  
pp. R34-R42 ◽  
Author(s):  
Takafumi Kato ◽  
Yuji Masuda ◽  
Hayato Kanayama ◽  
Norimasa Nakamura ◽  
Atsushi Yoshida ◽  
...  
Keyword(s):  
Heart Rate ◽  
Eye Movement ◽  
Rem Sleep ◽  
Muscle Activity ◽  
Guinea Pigs ◽  
Nrem Sleep ◽  
Activity Level ◽  
Jaw Muscles ◽  
High Activity Level ◽  
Motor Activities

Exaggerated jaw motor activities during sleep are associated with muscle symptoms in the jaw-closing rather than the jaw-opening muscles. The intrinsic activity of antagonistic jaw muscles during sleep remains unknown. This study aims to assess the balance of muscle activity between masseter (MA) and digastric (DG) muscles during sleep in guinea pigs. Electroencephalogram (EEG), electroocculogram, and electromyograms (EMGs) of dorsal neck, MA, and DG muscles were recorded with video during sleep-wake cycles. These variables were quantified for each 10-s epoch. The magnitude of muscle activity during sleep in relation to mean EMG activity of total wakefulness was up to three times higher for MA muscle than for DG muscle for nonrapid eye movement (NREM) and rapid-eye-movement (REM) sleep. Although the activity level of the two jaw muscles fluctuated during sleep, the ratio of activity level for each epoch was not proportional. Epochs with a high activity level for each muscle were associated with a decrease in δEEG power and/or an increase in heart rate in NREM sleep. However, this association with heart rate and activity levels was not observed in REM sleep. These results suggest that in guinea pigs, the magnitude of muscle activity for antagonistic jaw muscles is heterogeneously modulated during sleep, characterized by a high activity level in the jaw-closing muscle. Fluctuations in the activity are influenced by transient arousal levels in NREM sleep but, in REM sleep, the distinct controls may contribute to the fluctuation. The above intrinsic characteristics could underlie the exaggeration of jaw motor activities during sleep (e.g., sleep bruxism).

Sleep Disorders

2015 ◽  
Author(s):  
Sudhansu Chokroverty
Keyword(s):  
Sleep Apnea ◽  
Sleep Disorders ◽  
Eye Movement ◽  
Rem Sleep ◽  
Sleep Apnea Syndrome ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Circadian Rhythm Sleep Disorders ◽  
Apnea Syndrome ◽  
Sleep Mechanism

Recent research has generated an enormous fund of knowledge about the neurobiology of sleep and wakefulness. Sleeping and waking brain circuits can now be studied by sophisticated neuroimaging techniques that map different areas of the brain during different sleep states and stages. Although the exact biologic functions of sleep are not known, sleep is essential, and sleep deprivation leads to impaired attention and decreased performance. Sleep is also believed to have restorative, conservative, adaptive, thermoregulatory, and consolidative functions. This review discusses the physiology of sleep, including its two independent states, rapid eye movement (REM) and non–rapid eye movement (NREM) sleep, as well as functional neuroanatomy, physiologic changes during sleep, and circadian rhythms. The classification and diagnosis of sleep disorders are discussed generally. The diagnosis and treatment of the following disorders are described: obstructive sleep apnea syndrome, narcolepsy-cataplexy sydrome, idiopathic hypersomnia, restless legs syndrome (RLS) and periodic limb movements in sleep, circadian rhythm sleep disorders, insomnias, nocturnal frontal lobe epilepsy, and parasomnias. Sleep-related movement disorders and the relationship between sleep and psychiatric disorders are also discussed. Tables describe behavioral and physiologic characteristics of states of awareness, the international classification of sleep disorders, common sleep complaints, comorbid insomnia disorders, causes of excessive daytime somnolence, laboratory tests to assess sleep disorders, essential diagnostic criteria for RLS and Willis-Ekbom disease, and drug therapy for insomnia. Figures include polysomnographic recording showing wakefulness in an adult; stage 1, 2, and 3 NREM sleep in an adult; REM sleep in an adult; a patient with sleep apnea syndrome; a patient with Cheyne-Stokes breathing; a patient with RLS; and a patient with dream-enacting behavior; schematic sagittal section of the brainstem of the cat; schematic diagram of the McCarley-Hobson model of REM sleep mechanism; the Lu-Saper “flip-flop” model; the Luppi model to explain REM sleep mechanism; and a wrist actigraph from a man with bipolar disorder. This review contains 14 highly rendered figures, 8 tables, 115 references, and 5 MCQs.

Arousal and breathing responses to airway occlusion in healthy sleeping adults

1983 ◽  
Vol 55 (4) ◽  
pp. 1113-1119 ◽  
Author(s):  
F. G. Issa ◽  
C. E. Sullivan
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Progressive Increase ◽  
Total Occlusion ◽  
Airway Occlusion ◽  
Constant Bias ◽  
Bias Flow ◽  
Shallow Breathing

The arousal and breathing responses to total airway occlusion during sleep were measured in 12 normal subjects (7 males and 5 females) aged 25-36 yr. Subjects slept while breathing through a specially designed nosemask, which was glued to the nose with medical-grade silicon rubber. The lips were sealed together with a thin layer of Silastic. The nosemask was attached to a wide-bore (20 mm ID) rigid tube to allow a constant-bias flow of room air from a blower. Total airway occlusion was achieved by simultaneously inflating two rubber balloons fixed in the inspiratory and expiratory pipes. A total of 39 tests were done in stage III/IV nonrapid-eye movement (NREM) sleep in 11 subjects and 10 tests in rapid-eye-movement (REM) sleep in 5 subjects. The duration of total occlusion tolerated before arousal from NREM sleep varied widely (range 0.9-67.0 s) with a mean duration of 20.4 +/- 2.3 (SE) s. The breathing response to occlusion in NREM sleep was characterised by a breath-by-breath progressive increase in suction pressure achieved by an increase in the rate of inspiratory pressure generation during inspiration. In contrast, during REM sleep, arousal invariably occurred after a short duration of airway occlusion (mean duration 6.2 +/- 1.2 s, maximum duration 11.8 s), and the occlusion induced a rapid shallow breathing pattern. Our results indicate that total nasal occlusion during sleep causes arousal with the response during REM sleep being more predictable and with a generally shorter latency than that in NREM sleep.

scholarly journals A study on sleep apnea in patients with abnormal sewda type of depression

2020 ◽  
pp. 1-8
Author(s):  
Aman Gul ◽  
Nassirhadjy Memtily ◽  
Pirdun Mijit ◽  
Palidan Wushuer ◽  
Ainiwaer Talifu ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Sleep Onset ◽  
Sleep Time ◽  
Sleep Efficiency ◽  
Control Group ◽  
Poor Sleep ◽  
Sleep Structure ◽  
Maintenance Rate ◽  
Sleep Maintenance ◽  
Insomnia Symptoms

Objective: To preliminarily investigate the clinical features and PSG in abnormal sewda-type depressive insomnia. Methods: A total of 127 abnormal sewda-type depressive insomnia patients were evaluated with overnight PSG, and 32 normal participants were compared. Results: Patients with abnormal sewda-type depressive insomnia were compared with the control group; the sleep symptoms showed a long incubation period of sleep, low sleep maintenance rate, low sleep efficiency and poor sleep quality as well as daytime dysfunction. At process and continuity of sleep: Total sleep time, sleep efficiency, sleep maintenance rate in abnormal sewda-type depressive insomnia group were shorter than the control group. Wake after sleep onset, and sleep latency were longer than the control group. At sleep structure: N1 ratio and N2 ratio in depressive insomnia group were longer than the control group, N3 ratio and REM sleep ratio shorter than the control group. At REM index: REM latency, REM cycles, and REM sleep time were shorter than the control group. Conclusion: Insomnia symptoms in abnormal sewda-type depression comorbid insomnia patients were similar to the ordinary insomnia patients. The PSG characteristics had significant changes in sleep process, sleep structure and REM indicators. The severity of the abnormal sewda-type depression was closely related to REM indicators. Change of REM sleep characteristics may be the specificity, and these could be taken as reference in diagnosis and identification of abnormal sewda-type depressive insomnia.

scholarly journals Pathway-dependent regulation of sleep dynamics in a network model of the sleep-wake cycle

2019 ◽  
Author(s):  
Charlotte Héricé ◽  
Shuzo Sakata
Keyword(s):  
Computational Model ◽  
Eye Movement ◽  
Network Model ◽  
Rem Sleep ◽  
Synaptic Weight ◽  
Nrem Sleep ◽  
Cell Types ◽  
Brain Areas ◽  
Neuronal Populations ◽  
Neural Populations

AbstractSleep is a fundamental homeostatic process within the animal kingdom. Although various brain areas and cell types are involved in the regulation of the sleep-wake cycle, it is still unclear how different pathways between neural populations contribute to its regulation. Here we address this issue by investigating the behavior of a simplified network model upon synaptic weight manipulations. Our model consists of three neural populations connected by excitatory and inhibitory synapses. Activity in each population is described by a firing-rate model, which determines the state of the network. Namely wakefulness, rapid eye movement (REM) sleep or non-REM (NREM) sleep. By systematically manipulating the synaptic weight of every pathway, we show that even this simplified model exhibits non-trivial behaviors: for example, the wake-promoting population contributes not just to the induction and maintenance of wakefulness, but also to sleep induction. Although a recurrent excitatory connection of the REM-promoting population is essential for REM sleep genesis, this recurrent connection does not necessarily contribute to the maintenance of REM sleep. The duration of NREM sleep can be shortened or extended by changes in the synaptic strength of the pathways from the NREM-promoting population. In some cases, there is an optimal range of synaptic strengths that affect a particular state, implying that the amount of manipulations, not just direction (i.e., activation or inactivation), needs to be taken into account. These results demonstrate pathway-dependent regulation of sleep dynamics and highlight the importance of systems-level quantitative approaches for sleep-wake regulatory circuits.Author SummarySleep is essential and ubiquitous across animal species. Over the past half-century, various brain areas, cell types, neurotransmitters, and neuropeptides have been identified as part of a sleep-wake regulating circuitry in the brain. However, it is less explored how individual neural pathways contribute to the sleep-wake cycle. In the present study, we investigate the behavior of a computational model by altering the strength of connections between neuronal populations. This computational model is comprised of a simple network where three neuronal populations are connected together, and the activity of each population determines the current state of the model, that is, wakefulness, rapid-eye-movement (REM) sleep or non-REM (NREM) sleep. When we alter the connection strength of each pathway, we observe that the effect of such alterations on the sleep-wake cycle is highly pathway-dependent. Our results provide further insights into the mechanisms of sleep-wake regulation, and our computational approach can complement future biological experiments.

Sleep Disorders

2015 ◽  
Author(s):  
Sudhansu Chokroverty
Keyword(s):  
Sleep Apnea ◽  
Sleep Disorders ◽  
Eye Movement ◽  
Rem Sleep ◽  
Sleep Apnea Syndrome ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Circadian Rhythm Sleep Disorders ◽  
Apnea Syndrome ◽  
Sleep Mechanism

Recent research has generated an enormous fund of knowledge about the neurobiology of sleep and wakefulness. Sleeping and waking brain circuits can now be studied by sophisticated neuroimaging techniques that map different areas of the brain during different sleep states and stages. Although the exact biologic functions of sleep are not known, sleep is essential, and sleep deprivation leads to impaired attention and decreased performance. Sleep is also believed to have restorative, conservative, adaptive, thermoregulatory, and consolidative functions. This review discusses the physiology of sleep, including its two independent states, rapid eye movement (REM) and non–rapid eye movement (NREM) sleep, as well as functional neuroanatomy, physiologic changes during sleep, and circadian rhythms. The classification and diagnosis of sleep disorders are discussed generally. The diagnosis and treatment of the following disorders are described: obstructive sleep apnea syndrome, narcolepsy-cataplexy sydrome, idiopathic hypersomnia, restless legs syndrome (RLS) and periodic limb movements in sleep, circadian rhythm sleep disorders, insomnias, nocturnal frontal lobe epilepsy, and parasomnias. Sleep-related movement disorders and the relationship between sleep and psychiatric disorders are also discussed. Tables describe behavioral and physiologic characteristics of states of awareness, the international classification of sleep disorders, common sleep complaints, comorbid insomnia disorders, causes of excessive daytime somnolence, laboratory tests to assess sleep disorders, essential diagnostic criteria for RLS and Willis-Ekbom disease, and drug therapy for insomnia. Figures include polysomnographic recording showing wakefulness in an adult; stage 1, 2, and 3 NREM sleep in an adult; REM sleep in an adult; a patient with sleep apnea syndrome; a patient with Cheyne-Stokes breathing; a patient with RLS; and a patient with dream-enacting behavior; schematic sagittal section of the brainstem of the cat; schematic diagram of the McCarley-Hobson model of REM sleep mechanism; the Lu-Saper “flip-flop” model; the Luppi model to explain REM sleep mechanism; and a wrist actigraph from a man with bipolar disorder. This review contains 14 highly rendered figures, 8 tables, 115 references, and 5 MCQs.

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