scholarly journals The Statin Target HMG-Coenzyme a Reductase (Hmgcr) Regulates Sleep Homeostasis in Drosophila

2022 ◽  
Vol 15 (1) ◽  
pp. 79
Author(s):  
Ahmed M. Alsehli ◽  
Sifang Liao ◽  
Mohamed H. Al-Sabri ◽  
Lukas Vasionis ◽  
Archana Purohit ◽  
...  
Keyword(s):  
Sleep Disturbances ◽  
Coenzyme A ◽  
Sleep Latency ◽  
Statin Treatment ◽  
Sleep Regulation ◽  
Sleep Behavior ◽  
Sleep Episode ◽  
Sleep Homeostasis ◽  
The Impact ◽  
Coenzyme A Reductase

Statins, HMG Coenzyme A Reductase (HMGCR) inhibitors, are a first-line therapy, used to reduce hypercholesterolemia and the risk for cardiovascular events. While sleep disturbances are recognized as a side-effect of statin treatment, the impact of statins on sleep is under debate. Using Drosophila, we discovered a novel role for Hmgcr in sleep modulation. Loss of pan-neuronal Hmgcr expression affects fly sleep behavior, causing a decrease in sleep latency and an increase in sleep episode duration. We localized the pars intercerebralis (PI), equivalent to the mammalian hypothalamus, as the region within the fly brain requiring Hmgcr activity for proper sleep maintenance. Lack of Hmgcr expression in the PI insulin-producing cells recapitulates the sleep effects of pan-neuronal Hmgcr knockdown. Conversely, loss of Hmgcr in a different PI subpopulation, the corticotropin releasing factor (CRF) homologue-expressing neurons (DH44 neurons), increases sleep latency and decreases sleep duration. The requirement for Hmgcr activity in different neurons signifies its importance in sleep regulation. Interestingly, loss of Hmgcr in the PI does not affect circadian rhythm, suggesting that Hmgcr regulates sleep by pathways distinct from the circadian clock. Taken together, these findings suggest that Hmgcr activity in the PI is essential for proper sleep homeostasis in flies.

scholarly journals An Asymmetrical Hypothesis for the NREM-REM Sleep Alternation—What Is the NREM-REM Cycle?

2021 ◽  
Vol 15 ◽  
Author(s):  
Olivier Le Bon
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Refractory Period ◽  
High Variability ◽  
Oscillator Model ◽  
Rapid Eye Movement ◽  
Sleep Regulation ◽  
Short Term ◽  
Sleep Episode ◽  
Sleep Homeostasis

Since the discovery of rapid eye movement (REM) sleep (Aserinsky and Kleitman, 1953), sleep has been described as a succession of cycles of non-REM (NREM) and REM sleep episodes. The hypothesis of short-term REM sleep homeostasis, which is currently the basis of most credible theories on sleep regulation, is built upon a positive correlation between the duration of a REM sleep episode and the duration of the interval until the next REM sleep episode (inter-REM interval): the duration of REM sleep would therefore predict the duration of this interval. However, the high variability of inter-REM intervals, especially in polyphasic sleep, argues against a simple oscillator model. A new “asymmetrical” hypothesis is presented here, where REM sleep episodes only determine the duration of a proportional post-REM refractory period (PRRP), during which REM sleep is forbidden and the only remaining options are isolated NREM episodes or waking. After the PRRP, all three options are available again (NREM, REM, and Wake). I will explain why I think this hypothesis also calls into question the notion of NREM-REM sleep cycles.

scholarly journals Reduced sleep pressure in young children with autism

2019 ◽  
Author(s):  
Ayelet Arazi ◽  
Gal Meiri ◽  
Dor Danan ◽  
Analya Michaelovski ◽  
Hagit Flusser ◽  
...  
Keyword(s):  
Slow Wave ◽  
Sleep Disturbances ◽  
Sleep Onset ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Wave Activity ◽  
Slow Wave Activity ◽  
Sleep Regulation ◽  
Children With Asd ◽  
Sleep Homeostasis

AbstractStudy ObjectivesSleep disturbances and insomnia are highly prevalent in children with Autism Spectrum Disorder (ASD). Sleep homeostasis, a fundamental mechanism of sleep regulation that generates pressure to sleep as a function of wakefulness, has not been studied in children with ASD so far, and its potential contribution to their sleep disturbances remains unknown. Here, we examined whether slow wave activity (SWA), a measure that is indicative of sleep pressure, differs in children with ASD.MethodsIn this case-control study, we compared overnight electroencephalogram (EEG) recordings that were performed during Polysomnography (PSG) evaluations of 29 children with ASD and 23 typically developing children.ResultsChildren with ASD exhibited significantly weaker SWA power, shallower SWA slopes, and a decreased proportion of slow wave sleep in comparison to controls. This difference was largest during the first two hours following sleep onset and decreased gradually thereafter. Furthermore, SWA power of children with ASD was significantly, negatively correlated with the time of their sleep onset in the lab and at home, as reported by parents.ConclusionsThese results suggest that children with ASD may have a dysregulation of sleep homeostasis that is manifested in reduced sleep pressure. The extent of this dysregulation in individual children was apparent in the amplitude of their SWA power, which was indicative of the severity of their individual sleep disturbances. We, therefore, suggest that disrupted homeostatic sleep regulation may contribute to sleep disturbances in children with ASD.Statement of significanceSleep disturbances are apparent in 40-80% of children with autism. Homeostatic sleep regulation, a mechanism that increases the pressure to sleep as a function of prior wakefulness, has not been studied in children with autism. Here, we compared Polysomnography exams of 29 children with autism and 23 matched controls. We found that children with autism exhibited reduced slow-wave-activity power and shallower slopes, particularly during the first two hours of sleep. This suggests that they develop less pressure to sleep. Furthermore, the reduction in slow-wave-activity was associated with the severity of sleep disturbances as observed in the laboratory and as reported by parents. We, therefore, suggest that disrupted homeostatic sleep regulation may contribute to sleep disturbances of children with autism.

Homeostatic sleep regulation in habitual short sleepers and long sleepers

1996 ◽  
Vol 270 (1) ◽  
pp. R41-R53 ◽  
Author(s):  
D. Aeschbach ◽  
C. Cajochen ◽  
H. Landolt ◽  
A. A. Borbely
Keyword(s):  
Rem Sleep ◽  
Process Model ◽  
Sleep Latency ◽  
Spectral Power ◽  
Spectral Power Density ◽  
Sleep Time ◽  
Sleep Regulation ◽  
Sleep Episode ◽  
Rem Density ◽  
Electroencephalogram Eeg

Homeostatic sleep regulation in habitual short sleepers (sleep episode < 6 h, n = 9) and long sleepers (> 9 h, n = 7) was investigated by studying their sleep structure and sleep electroencephalogram (EEG) during baseline conditions and after prolonging their habitual waking time by 24 h. In each sleep episode, total sleep time was > 3 h longer in the long sleepers than in the short sleepers. Sleep deprivation decreased sleep latency and rapid eye movement (REM) density in REM sleep more in long sleepers than in short sleepers. The enhancement of EEG slow-wave activity (SWA; spectral power density in the 0.75-4.5 Hz range) in non-REM sleep after sleep loss was larger in long sleepers (47%) than in short sleepers (19%). This difference in the SWA response was predicted by the two-process model of sleep regulation on the basis of the different sleep durations. The results indicate that short sleepers live under a higher “non-REM sleep pressure” than long sleepers. However, the two groups do not differ with respect to the homeostatic sleep regulatory mechanisms.

scholarly journals The Negative Effect of Carpal Tunnel Syndrome on Sleep Quality

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ashish Patel ◽  
Maya Deza Culbertson ◽  
Archit Patel ◽  
Jenifer Hashem ◽  
Jinny Jacob ◽  
...  
Keyword(s):  
Carpal Tunnel Syndrome ◽  
Sleep Quality ◽  
Carpal Tunnel ◽  
Sleep Disturbances ◽  
Sleep Latency ◽  
Sleep Time ◽  
Quality Parameters ◽  
Negative Effect ◽  
Tunnel Syndrome ◽  
The Impact

Objective. Sleep disturbances are common in patients with carpal tunnel syndrome (CTS). This study investigates the impact of CTS on sleep quality and clarifies the magnitude of this relationship.Methods. This is a prospective investigation of patients with CTS. Patients responded to the Levine-Katz Carpal Tunnel and the Pittsburgh Sleep Quality Index (PSQI) questionnaires to assess symptom severity and quality, respectively. Descriptive and bivariate analyses summarized the findings and assessed the correlations between CTS severity and sleep quality parameters.Results. 66 patients (53F, 13M) were enrolled. Patients reported a sleep latency of 30.0 (±22.5) minutes, with a total sleep time of 5.5 (±1.8) hours nightly. Global PSQI score was 9.0 (±3.8); 80% of patients demonstrated a significant reduction in sleep quality (global PSQI score>5). Increased CTS symptom and functional severity both resulted in a significant reduction in quality and time asleep. Both significantly correlated with subjective sleep latency, sleep disturbance, use of sleep promoting medications, daytime dysfunction, and overall global PSQI score.Conclusions. The findings confirm the correlation of sleep disturbances to CTS, that is, significant reduction of sleep duration and a correlation to sleep quality. Patients sleep 2.5 hours less than recommended and are at risk for comorbid conditions.

scholarly journals Reduced sleep pressure in young children with autism

SLEEP ◽  
2019 ◽  
Vol 43 (6) ◽  
Author(s):  
Ayelet Arazi ◽  
Gal Meiri ◽  
Dor Danan ◽  
Analya Michaelovski ◽  
Hagit Flusser ◽  
...  
Keyword(s):  
Slow Wave ◽  
Sleep Disturbances ◽  
Slow Wave Sleep ◽  
Sleep Onset ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Potential Contribution ◽  
Sleep Regulation ◽  
Children With Asd ◽  
Sleep Homeostasis

Abstract Study Objectives Sleep disturbances and insomnia are highly prevalent in children with Autism Spectrum Disorder (ASD). Sleep homeostasis, a fundamental mechanism of sleep regulation that generates pressure to sleep as a function of wakefulness, has not been studied in children with ASD so far, and its potential contribution to their sleep disturbances remains unknown. Here, we examined whether slow-wave activity (SWA), a measure that is indicative of sleep pressure, differs in children with ASD. Methods In this case-control study, we compared overnight electroencephalogram (EEG) recordings that were performed during Polysomnography (PSG) evaluations of 29 children with ASD and 23 typically developing children. Results Children with ASD exhibited significantly weaker SWA power, shallower SWA slopes, and a decreased proportion of slow-wave sleep in comparison to controls. This difference was largest during the first 2 hours following sleep onset and decreased gradually thereafter. Furthermore, SWA power of children with ASD was significantly negatively correlated with the time of their sleep onset in the lab and at home, as reported by parents. Conclusions These results suggest that children with ASD may have a dysregulation of sleep homeostasis that is manifested in reduced sleep pressure. The extent of this dysregulation in individual children was apparent in the amplitude of their SWA power, which was indicative of the severity of their individual sleep disturbances. We, therefore, suggest that disrupted homeostatic sleep regulation may contribute to sleep disturbances in children with ASD.

scholarly journals Dietary α-Tocopherol Attenuates the Impact of γ-Tocotrienol on Hepatic 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity in Chickens

1996 ◽  
Vol 126 (2) ◽  
pp. 389-394 ◽  
Author(s):  
Asaf A. Qureshi ◽  
Bradley C. Pearce ◽  
Rosnah M. Nor ◽  
A. Gapor ◽  
David M. Peterson ◽  
...  
Keyword(s):  
Coenzyme A ◽  
Reductase Activity ◽  
The Impact ◽  
Coenzyme A Reductase

029 Median preoptic dual control over sleep regulation

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A13-A14
Author(s):  
Natalia Machado ◽  
William Todd ◽  
Clifford Saper
Keyword(s):  
Nrem Sleep ◽  
Underlying Mechanism ◽  
Brain Regions ◽  
Sleep Cycle ◽  
Sleep Regulation ◽  
Sleep Behavior ◽  
Sleep Homeostasis ◽  
Psychological Stressor ◽  
Sleep Control

Abstract Introduction Previous studies suggest that the median preoptic nucleus (MnPO) plays an important role in regulating the wake-sleep cycle and in particular homeostatic sleep drive. However, the precise cellular phenotypes, targets and central mechanisms by which the MnPO neurons regulate the wake-sleep cycle remain unknown. Both glutamatergic (Vglut2+) and GABAergic (Vgat+) MnPO neurons innervate brain regions implicated in sleep promotion and maintenance, suggesting that both cell types may participate on sleep control. Methods In this study, we used two genetically-targeted approaches associated with electroencephalographic (EEG) and electromyographic (EMG) recordings in Vgat-IRES-cre and Vglut2-IRES-cre mice to investigate the role of the MnPOVgat and MnPOVglut2 neurons in modulating wake-sleep behavior. Results First, using a chemogenetic approach, we found that activation of MnPOVgat neurons reduced the latency for the first NREM sleep episode, produced an increase in NREM sleep and reduced wakefulness. Then, to test the role of MnPOVgat and MnPOVglut2 neurons in regulating sleep homeostasis, we recorded EEG and EMG responses in mice that had the Vgat+ or Vglut2+ neurons deleted from the MnPO. After deletion of MnPOVgat neurons, mice showed a reduction of NREM sleep and an increase in wakefulness during the light phase. Deletion of MnPOVgat neurons also reduced sleep recovery after 4 hours of sleep deprivation (SD). On the other hand, deletion of the MnPOVglut2 neurons did not change the wake-sleep cycle during the 24h baseline condition, but prevented the sleep recovery immediately after SD. To understand the underlying mechanism in preventing sleep recovery in both MnPOVglut2- and MnPOVgat-deleted mice groups, we exposed these animals to a psychological stress protocol. In response to a psychological stressor, mice with deletion of glutamatergic, but not GABAergic MnPO neurons, had an exacerbation of the stress-induced insomnia. Conclusion Our results suggest that both neuron populations differentially participate in wake-sleep control, with MnPOVgat neurons being critically involved in sleep homeostasis, and MnPOVglut2 neurons promoting sleep during allostatic (stressful) challenges. Support (if any) NIH Grants NS085477, NS072337, HL095491 and Sleep Research Society Foundation (Award 026-JP-20).

Vitamin D and Sleep Regulation: Is there a Role for Vitamin D?

2020 ◽  
Vol 26 (21) ◽  
pp. 2492-2496 ◽  
Author(s):  
Fiammetta Romano ◽  
Giovanna Muscogiuri ◽  
Elea Di Benedetto ◽  
Volha V. Zhukouskaya ◽  
Luigi Barrea ◽  
...  
Keyword(s):  
Vitamin D ◽  
Sleep Disorders ◽  
Vitamin D Deficiency ◽  
Sleep Apnea Syndrome ◽  
Regulatory Mechanisms ◽  
Sleep Regulation ◽  
Vitamin D Receptors ◽  
Obstructive Sleep ◽  
The Impact

Background: Vitamin D exerts multiple pleiotropic effects beyond its role in calcium-phosphate metabolism. Growing evidence suggests an association between hypovitaminosis D and sleep disorders, thus increasing the interest in the role of this vitamin in the regulatory mechanisms of the sleep-wake cycle. Objective: The study aimed to explore and summarize the current knowledge about the role of vitamin D in sleep regulation and the impact of vitamin D deficiency on sleep disorders. Methods: The main regulatory mechanisms of vitamin D on sleep are explained in this study. The literature was scanned to identify clinical trials and correlation studies showing an association between vitamin D deficiency and sleep disorders. Results: Vitamin D receptors and the enzymes that control their activation and degradation are expressed in several areas of the brain involved in sleep regulation. Vitamin D is also involved in the pathways of production of Melatonin, the hormone involved in the regulation of human circadian rhythms and sleep. Furthermore, vitamin D can affect sleep indirectly through non-specific pain disorders, correlated with alterations in sleep quality, such as restless legs syndrome and obstructive sleep apnea syndrome. Conclusions: : Vitamin D has both a direct and an indirect role in the regulation of sleep. Although vitamin D deficiency has been associated to sleep disorders, there is still scant evidence to concretely support the role of vitamin D supplementation in the prevention or treatment of sleep disturbances; indeed, more intervention studies are needed to better clarify these aspects.

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