Reduced Rapid Eye Movement Sleep Research Articles

The Kir channel in the nucleus tractus solitarius integrates the chemosensory system with REM sleep executive machinery for homeostatic balance

The locus coeruleus (LC), nucleus tractus solitarius (NTS), and retrotrapezoid nucleus (RTN) are critical chemosensory regions in the brainstem. In the LC, acid-sensing ion channels and proton pumps serve as H+ sensors and facilitate the transition from non-rapid eye movement (NREM) to rapid eye movement (REM) sleep. Interestingly, the potassium inward rectifier (KIR) channels in the LC, NTS, and RTN also act as H+-sensors and are a primary target for improving sleep in obstructive sleep apnea and Rett syndrome patients. However, the role of Kir channels in NREM to REM sleep transition for H+ homeostasis is not known. Male Wistar rats were surgically prepared for chronic sleep–wake recording and drug delivery into the LC, NTS, and RTN. In different animal cohorts, microinjections of the Kir channel inhibitor, barium chloride (BaCl2), at concentrations of 1 mM (low dose) and 2 mM (high dose) in the LC and RTN significantly increased wakefulness and decreased NREM sleep. However, BaCl2 microinjection into the LC notably reduced REM sleep, whereas it didn’t change in the RTN-injected group. Interestingly, BaCl2 microinjections into the NTS significantly decreased wakefulness and increased the percent amount of NREM and REM sleep. Additionally, with the infusion of BaCl2 into the NTS, the mean REM sleep episode numbers significantly increased, but the length of the REM sleep episode didn’t change. These findings suggest that the Kir channels in the NTS, but not in the LC and RTN, modulate state transition from NREM to REM sleep.

Insomnia and REM sleep instability.

In this narrative review, we give an overview of the concept of rapid eye movement sleep instability and its reported implications in the context of insomnia. The term rapid eye movement sleep instability was coined to describe the observation of a modified rapid eye movement quality in insomnia, characterized by an increased tendency of perceiving rapid eye movement sleep as wake, a small but consistent rapid eye movement sleep reduction and an increased rapid eye movement sleep arousal index. Current research highlights relationships that are transdiagnostic in nature, corresponding to the known interaction of insomnia with many psychiatric disorders, and showing relationships to chronic stress and anxiety disorders.

Effect of Sleep Restriction during Pregnancy on Fetal Brain Programming and Neurocognitive Development of Offspring: A Review

We spend one-third of our lives in sleep, yet the core function of it still remains an enigma due to underlying complex neural processing in this altered state of consciousness. Sleep requirement varies with phase of development. Neonates spent about 85% of their time in sleep, which is polyphasic in nature. Gradually, this pattern takes the shape of a monophasic sleep in adolescents and adults, with changing micro- and macroarchitecture in every phase. Deprivation of sleep in adults impairs learning and memory, and reduces theta coherence among hippocampus and amygdale during sleep. However, sleep loss during pregnancy can affect the ontogenetic development of networks for sleep–wakefulness and the cognitive development of offspring. Even in normal pregnancy, poor sleep quality, reduced rapid eye movement (REM) sleep, and sleep fragmentation are common observation during the last trimester of pregnancy. Delta power, a marker for the homeostatic drive for sleep, in the NREM sleep during the last trimester of pregnancy and postpartum is increased. However, further sleep loss during late pregnancy is a growing concern. Neonates that are born to the total sleep-restricted dams present significant alterations in their emotional development (symptoms of hyperactivity, increased risk-taking behavior during periadolescence) and immature sleep–wakefulness patterns. The REM sleep restriction during late pregnancy elicits depressionlike traits in neonates, which persist until middle age. For a healthy development of brain and body, thorough understanding of the dynamic nature of sleep in relation to age and state (pregnancy) is instrumental in preventing the above-mentioned conditions of prenatal origin. Although sleep is essential for an active brain (for work during day), it remains an underestimated phenomenon. This review highlights the importance of sleep during pregnancy for a healthy brain network programming in offspring.

A ketogenic diet containing medium-chain triglycerides reduces REM sleep duration without significant influence on mouse circadian phenotypes

Ketogenic diets (KDs) affect the circadian rhythms of behavior and clock gene expression in experimental animals. However, these diets were designed to simulate a fasting state; thus, whether these effects are caused by diet-induced ketogenesis or persistent starvation is difficult to distinguish. The present study aimed to define the effects of a KD containing medium-chain triglycerides (MCT-KD) that increase blood ketone levels without inducing carbohydrate starvation, on circadian rhythms and sleep regulation. Mice were fed with a normal diet (CTRL) or MCT-KD for 2 weeks. Blood β-hydroxybutyrate levels were significantly increased up to 2 mM by the MCT-KD, whereas body weight gain and blood glucose levels were identical between the groups, suggesting that ketosis accumulated without carbohydrate starvation in the MCT-KD mice. Circadian rhythms of wheel-running activity and core body temperature were almost identical, although wheel-running was slightly reduced in the MCT-KD mice. The circadian expression of the core clock genes, Per1, Per2, Bmal1, and Dbp in the hypothalamus, heart, liver, epididymal adipose tissues, and skeletal muscle were almost identical between the CTRL and MCT-KD mice, whereas the amplitude of hepatic Per2 and adipose Per1 expression was increased in MCT-KD mice. The MCT-KD reduced the duration of rapid-eye-movement (REM) sleep without affecting the duration of non-REM sleep and the duration of wakefulness. These findings suggested that the impact of ketone bodies on circadian systems are limited, although they might reduce locomotor activity and REM sleep duration.

Comparison of sleep deprivation and a low dose of ketamine on sleep and the electroencephalogram in Brown Norway rats.

Ketamine is known for its antidepressant effects, but the mechanism underlying this effect remains largely unclear. In contrast to most antidepressant drugs, the action of ketamine is rapid, suggesting a different mode of action. A rapid antidepressant effect is also observed following sleep deprivation (SD). In the present study, we aimed to evaluate the effect of a 6-h SD and acute ketamine treatment on vigilance states, locomotor activity, and electroencephalogram (EEG) power density spectra in Brown Norway rats under constant condition over 2 recording days. After SD and after the initial waking period induced by ketamine, both treatments induced a similar increase in non-rapid eye movement (NREM) sleep and EEG slow-wave activity (SWA) in NREM sleep. Rapid eye movement (REM) sleep was reduced immediately after both treatments but was recovered later only after the SD. The effects on the waking EEG differed between the treatments, with a faster theta peak during and after SD, and no change in the waking spectrum after ketamine. In conclusion, SD and ketamine both lead to an acute increment in NREM sleep SWA as well as in a reduction in REM sleep. The results suggest that selective suppression of REM sleep, combined with enhancement of SWA during NREM may be effective in the treatment of depression.

The Effect of Obstructive Sleep Apnea on Sleep-dependent Emotional Memory Consolidation.

Rationale: A growing body of evidence suggests that sleep is critical for the adaptive processing and consolidation of emotional information into long-term memory. Previous research has indicated that emotional components of scenes particularly benefit from sleep in healthy groups, yet sleep-dependent emotional memory processes remain unexplored in clinical cohorts, including those with obstructive sleep apnea (OSA). This line of research is important as it will add to the understanding of how disrupted sleep in OSA contributes to both impaired cognition and emotion dysregulation. Objectives: To test the hypothesis that individuals with OSA will have impaired sleep-dependent memory consolidation, with the greatest impact being on memory for emotional content. Methods: In this study, a group of newly diagnosed patients with OSA (n = 26; 10 female; average age, 42.5 years) and a matched group of healthy control subjects (n = 24; 13 female; average age, 37 years) were enrolled in the study at Beth Israel Deaconess Medical Center. Participants encoded scenes with negative or neutral foreground objects placed on neutral backgrounds before a night of polysomnographically recorded sleep. In the morning, they completed a recognition test in which old and new scene objects and backgrounds, presented separately and one at a time, were judged as old, new, or similar compared with what had been previously viewed. Results: Patients with OSA had a deficit in recognition memory for the scenes. Overall recognition (the ability to recognize old items as either old or similar) was impaired across all scene elements, both negative and neutral objects and backgrounds, whereas specific recognition (correctly identifying old items as old) was impaired only for negative objects. Across all participants, successful overall recognition correlated positively with sleep efficiency and rapid eye movement (REM) sleep, whereas successful specific memory recognition correlated only with REM sleep. Conclusions: Our findings indicate that fragmented sleep and reduced REM sleep, both hallmarks of OSA, are associated with disruptions in general memory impairment and veridical memory for emotional content, which could alter emotional regulation and contribute to comorbid emotional distress in OSA.

Effect of levetiracetam on nocturnal sleep in patients with epilepsy

The purpose of our study was the evaluation of the effect of 2,000 mg levetiracetam monotherapy over a 3-month period on nocturnal sleep in patients with epilepsy. Levetiracetam (LEV) is a novel antiepileptic drug with a unique anticonvulsive mechanism of action. It has been commonly reported to cause sleep disruption and daytime sleepiness in epilepsy patients. Its advantages (its broad antiepileptic spectrum, optimal pharmacokinetics, good safety and tolerability) have led to its frequent use in clinical practice, although little is yet known about LEV's effect on nocturnal sleep architecture. The effect of LEV on nocturnal sleep was assessed through a full-night lab polysomnography (PSG), followed by a four-nap multiple sleep latency test. Both procedures were performed at baseline and after three months of LEV treatment. The dynamics of seven main PSG variables was evaluated prior to, and three months after, LEV therapy. Twenty five patients with newly diagnosed or untreated epilepsy completed the study. We found no statistically significant difference at baseline and after LEV therapy in the following sleep parameters: total sleep time, sleep onset, wake after sleep onset, N1 stage and rapid eye movement (REM) sleep (minutes and percentages), and latency of all sleep stages including REM sleep. However, we found a statistically significant increase in the number of awakenings and arousals, an increase in N2 and a decrease in N3 stages (minutes and percentages) after therapy. We also observed an increase in N1 stage and a trend toward a reduction in REM sleep (in both minutes and percentages), but they did not reach statistical significance. Levetiracetam 2,000 mg/day does not affect sleep continuity and may be considered a sleep-friendly antiepileptic drug.

Effect of Combined Dexmedetomidine and Sevoflurane Sedation on Sleep Homeostasis in Sprague Dawley Rat

BackgroundThe effect of continuous long‐term administration of sedative‐hypnotics ‐ as occurs in the intensive and perioperative care ‐ on sleep homeostasis is not completely understood. Ongoing studies in our laboratory have shown that sedation produced by continuous infusion (8 h) of dexmedetomidine (DEX, 0.5‐1.0 μg/kg/min) increased wake state (WAKE), decreased slow‐wave sleep (SWS) and reduced rapid eye movement sleep (REMS) in the post‐sedation period, while sedation with continuous (8 h) sevoflurane (SEVO, 2.5‐3.0%) administration did not affect WAKE or SWS but increased post‐sedation REMS [1]. In the current study, to investigate the possibility of a synergistic effect of DEX and SEVO on sleep homeostasis, we maintained the rats on sedation (8 h) produced by simultaneous administration of DEX and SEVO and quantified the effect on post‐sedation sleep‐wake states (48 h).MethodsAdult male and female Sprague Dawley rats (n=4) were surgically prepared for sleep‐wake recordings and a catheter was chronically positioned in the jugular vein for DEX or lactated Ringer’s (control) infusion. Each rat received 8 h of continuous (10:00 am – 6:00 pm) combined administration of SEVO (0.5‐1.0%) and intravenous DEX (0.1 ug/kg/min), and lactated Ringer’s on a different day with inter‐experiment interval of at least 5‐7 days. The SEVO and DEX concentrations were titrated to maintain loss of righting reflex, which is a surrogate for loss of consciousness in rodents. Post‐sedation sleep‐wake data were recorded for 48 h and manually scored in 4 s epochs into WAKE, SWS, and REMS.ResultsThe total time (in minutes) spent in WAKE during the first 12 h post‐sedation period was comparable to that observed after lactated Ringer’s infusion (mean ± standard deviation: 87.78 ± 13.58 after lactated Ringer’s vs 98.59 ± 11.71 after sedation). Similar trend was observed for SWS (mean ± standard deviation: 65.95 ± 10.37 after lactated Ringer’s vs 75.08 ± 12.60 after sedation) while REMS was reduced by 78.68% during the first 12 h post‐sedation period as compared to that observed after lactated Ringer’s infusion (mean ± standard deviation: 25.36 ± 6.715 after lactated Ringer’s vs 5.41 ± 3.30 after sedation). The time spent in WAKE, SWS, and REMS during the remaining 36 h of post‐sedation period was comparable to that after lactated Ringer’s infusion. Compared to the individual administration of DEX and SEVO, as reported previously from our lab [1], combined administration of SEVO and DEX in the current study required 5‐10 times less dose to maintain the loss of righting reflex.ConclusionThe effect of combined sedation with SEVO and DEX are distinct from the effects after individual administration of these sedatives, suggesting minimal interruption of sleep homeostatic processes leading to a sleep profile that more closely mirrors the natural sleep‐wake states.References Parkar A, Liu T, Fryzel A, Groenhout T, Mashour GA and Pal D (2020) Effect of prolonged sedation with dexmedetomidine, midazolam, propofol, or sevoflurane on sleep homeostasis in rat. J Neurosurgical Anesthesiology, Vol 32, No 4, Page 403, Abstract no SNACC‐387.

Effects of Non‐contingent and Self‐administered Oxycodone on Sleep Architecture in Rats

Opioid use disorder (OUD) is an ongoing global public health concern. Opioid analgesics such as oxycodone are major contributors to this epidemic because of their abuse potential. Thus, understanding acute and long-term effects of opioid exposure is critical. Sleep disturbances are commonly reported yet understudied symptoms of OUD commonly associated with relapse. Normalizing the sleep disturbances associated with OUD could be a novel therapeutic approach for relapse prevention. No study to date has assessed progressive changes in sleep/wake architecture following contingent or non-contingent oxycodone exposure in animals. In the present studies, effects of oxycodone on sleep/wake architecture and quantitative electroencephalography (EEG) were examined in freely moving, Sprague-Dawley rats implanted with EEG surface electrodes and wireless transmitters. 24 hr EEG home cage recordings were scored manually as wake, rapid eye movement (REM) and non-REM (NREM) sleep. In one cohort, effects of acute, noncontingent oxycodone (1-3 mg/kg; sc) were examined when administered 2 hr into the light cycle. Oxycodone dose-dependently increased time awake and reduced NREM and REM sleep duration. Spectral power analysis showed that oxycodone dose-dependently increased high frequency gamma power (50-100Hz). In a second cohort, rats were implanted with both EEG implants and intravenous jugular catheters to examine effects of oxycodone self-administration (SA) on sleep. Rats were trained to self-administer sucrose pellets on a fixed ratio 3 (FR3) schedule of reinforcement during the first 2 hours of the dark cycle. Next, rats were divided into two groups; half continued to self-administer sucrose pellets, while the other self-administered oxycodone (0.056 mg/kg/inf for 7 days; then 0.1 mg/kg/inf for 10 days). On average, rats self-administered 1.04 mg/kg oxycodone per 2-hr session. Rats then underwent response extinction for 5 days where the reinforcer and light cues were absent followed by a single light-cue elicited reinstatement session. EEG was recorded from the home cages for the remaining 22 hours per day. Preliminary data suggest that, compared to the last day of sucrose pellet SA, oxycodone SA increased time awake and decreased NREM and REM sleep. These changes were not seen in rats self-administering sucrose pellets. The increase in wake duration persisted throughout oxycodone SA sessions, but the reduction in REM sleep dissipated over time. Ongoing analyses are examining sleep during abstinence to determine whether abstinence-related changes in sleep occur in a similar manner to other illicit drug classes. The effects of noncontingent oxycodone are more prominent than self-administered despite similar total daily intake. Self-administration paradigms yielding higher daily intake may be necessary to engender greater sleep disturbances. Although preliminary, understanding the direct pharmacological effects of oxycodone self-administration on sleep will be beneficial to examine potential novel pharmacotherapies to normalize sleep disturbances associated with OUD.

MicroRNAs in Basolateral Amygdala Associated with Stress and Fear Memories Regulate Rapid Eye Movement Sleep in Rats.

Stress-related sleep disturbances are distressing clinical symptoms in posttraumatic stress disorder patients. Intensely stressful events and their memories change rapid eye movement (REM) sleep in animal models. REM sleep varies with individual differences of stress resilience or vulnerability. The basolateral amygdala (BLA) is a primary mediator of the effects of stress and fear memories on sleep. However, the molecular mechanisms in BLA regulating the effects of fear conditioning, shock training (ST) and context re-exposure (CTX) on REM sleep are not well known. MicroRNAs (miRNAs) are small, non-coding RNAs and posttranscriptional gene regulators of diverse biological processes. The aim of this study is to investigate ST- and CTX-altered miRNAs in the BLA of resilience and vulnerable animals and on REM sleep regulation. MiRNAs expression profiles in BLA were generated following ST and CTX using the Taqman Low Density rodent microRNA array. The altered BLA miRNAs expression and REM sleep reduction observed in ST and CTX vulnerable animals. AntagomiR-221 microinjection into BLA for one of the upregulated miRNAs, miR-221 in BLA, attenuated the REM sleep reduction. This study suggests that miRNAs in the BLA may play a significant role in mediating the effects of stress and fear memories on REM sleep.

The Effects of Daytime Psilocybin Administration on Sleep: Implications for Antidepressant Action.

Serotonergic agonist psilocybin is a psychedelic with antidepressant potential. Sleep may interact with psilocybin’s antidepressant properties like other antidepressant drugs via induction of neuroplasticity. The main aim of the study was to evaluate the effect of psilocybin on sleep architecture on the night after psilocybin administration. Regarding the potential antidepressant properties, we hypothesized that psilocybin, similar to other classical antidepressants, would reduce rapid eye movement (REM) sleep and prolong REM sleep latency. Moreover, we also hypothesized that psilocybin would promote slow-wave activity (SWA) expression in the first sleep cycle, a marker of sleep-related neuroplasticity. Twenty healthy volunteers (10 women, age 28–53) underwent two drug administration sessions, psilocybin or placebo, in a randomized, double-blinded design. Changes in sleep macrostructure, SWA during the first sleep cycle, whole night EEG spectral power across frequencies in non-rapid eye movement (NREM) and REM sleep, and changes in subjective sleep measures were analyzed. The results revealed prolonged REM sleep latency after psilocybin administration and a trend toward a decrease in overall REM sleep duration. No changes in NREM sleep were observed. Psilocybin did not affect EEG power spectra in NREM or REM sleep when examined across the whole night. However, psilocybin suppressed SWA in the first sleep cycle. No evidence was found for sleep-related neuroplasticity, however, a different dosage, timing, effect on homeostatic regulation of sleep, or other mechanisms related to antidepressant effects may play a role. Overall, this study suggests that potential antidepressant properties of psilocybin might be related to changes in sleep.

Association of Rapid Eye Movement Sleep With Mortality in Middle-aged and Older Adults

Rapid eye movement (REM) sleep has been linked with health outcomes, but little is known about the relationship between REM sleep and mortality. To investigate whether REM sleep is associated with greater risk of mortality in 2 independent cohorts and to explore whether another sleep stage could be driving the findings. This multicenter population-based cross-sectional study used data from the Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study and Wisconsin Sleep Cohort (WSC). MrOS participants were recruited from December 2003 to March 2005, and WSC began in 1988. MrOS and WSC participants who had REM sleep and mortality data were included. Analysis began May 2018 and ended December 2019. All-cause and cause-specific mortality confirmed with death certificates. The MrOS cohort included 2675 individuals (2675 men [100%]; mean [SD] age, 76.3 [5.5] years) and was followed up for a median (interquartile range) of 12.1 (7.8-13.2) years. The WSC cohort included 1386 individuals (753 men [54.3%]; mean [SD] age, 51.5 [8.5] years) and was followed up for a median (interquartile range) of 20.8 (17.9-22.4) years. MrOS participants had a 13% higher mortality rate for every 5% reduction in REM sleep (percentage REM sleep SD = 6.6%) after adjusting for multiple demographic, sleep, and health covariates (age-adjusted hazard ratio, 1.12; fully adjusted hazard ratio, 1.13; 95% CI, 1.08-1.19). Results were similar for cardiovascular and other causes of death. Possible threshold effects were seen on the Kaplan-Meier curves, particularly for cancer; individuals with less than 15% REM sleep had a higher mortality rate compared with individuals with 15% or more for each mortality outcome with odds ratios ranging from 1.20 to 1.35. Findings were replicated in the WSC cohort despite younger age, inclusion of women, and longer follow-up (hazard ratio, 1.17; 95% CI, 1.03-1.34). A random forest model identified REM sleep as the most important sleep stage associated with survival. Decreased percentage REM sleep was associated with greater risk of all-cause, cardiovascular, and other noncancer-related mortality in 2 independent cohorts.

Progressive Changes in Sleep and Its Relations to Amyloid-β Distribution and Learning in Single App Knock-In Mice.

Alzheimer’s disease (AD) patients often suffer from sleep disturbances. Alterations in sleep, especially rapid eye movement sleep (REMS), can precede the onset of dementia. To accurately characterize the sleep impairments accompanying AD and their underlying mechanisms using animal models, it is crucial to use models in which brain areas are affected in a manner similar to that observed in the actual patients. Here, we focused on AppNL-G-F mice, in which expression levels and patterns of mutated amyloid precursor protein (APP) follow the endogenous patterns. We characterized the sleep architecture of male AppNL-G-F homozygous and heterozygous mice at two ages (six and 12 months). At six months, homozygous mice exhibited reduced REMS, which was further reduced at 12 months together with a slight reduction in non-REMS (NREMS). By contrast, heterozygous mice exhibited an overall normal sleep architecture. Homozygous mice also exhibited decreased electroencephalogram γ to δ power ratio during REMS from six months, resembling the electroencephalogram slowing phenomenon observed in preclinical or early stages of AD. In addition, homozygous mice showed learning and memory impairments in the trace fear conditioning (FC) at both ages, and task performance strongly correlated with REMS amount at 12 months. Finally, histologic analyses revealed that amyloid-β accumulation in the pontine tegmental area and ventral medulla followed a course similar to that of the REMS reduction. These findings support the notion that changes in REMS are an early marker of AD and provide a starting point to address the mechanism of sleep deficits in AD and the effects on cognition.

Activation of Preoptic GABAergic or Glutamatergic Neurons Modulates Sleep-Wake Architecture, but Not Anesthetic State Transitions.

The precise mechanism of general anesthesia remains unclear. In the last two decades, there has been considerable focus on the hypothesis that anesthetics co-opt the neural mechanisms regulating sleep. This hypothesis is supported by ample correlative evidence at the level of sleep-promoting nuclei, but causal investigations of potent inhaled anesthetics have not been conducted. Here, we tested the hypothesis that chemogenetic activation of discrete neuronal subpopulations within the median preoptic nucleus (MnPO) and ventrolateral preoptic nucleus (VLPO) of the hypothalamus would modulate sleep/wake states and alter the time to loss and resumption of consciousness associated with isoflurane, a potent halogenated ether in common clinical use. We show that activating MnPO/VLPO GABAergic or glutamatergic neurons does not alter anesthetic induction or recovery time. However, activation of these neuronal subpopulations did alter sleep-wake architecture. Notably, we report the novel finding that stimulation of VLPO glutamatergic neurons causes a strong increase in wakefulness. We conclude that activation of preoptic GABAergic or glutamatergic neurons that increase sleep or wakefulness does not substantively influence anesthetic state transitions. These data indicate that the correlative evidence for a mechanistic overlap of sleep and anesthesia at the level of an individual nucleus might not necessarily have strong causal significance.

Night-time cardiac autonomic modulation as a function of sleep–wake stages is modified in otherwise healthy overweight adolescents

ObjectiveEven though sympathetic dominance during the daytime period is well known, currently, scarce data exist on autonomic nervous system (ANS) regulation during sleep in pediatric obesity. We aimed to evaluate sleep cardiac ANS regulation in normal-weight (NW) and overweight and obese (OW) adolescents. Patients/methodsIn this study, 60 healthy adolescents (15.7 ± 0.7 years) belonging to a birth cohort since infancy were classified based on body mass index percentiles criteria as: OW (N = 27) or NW (N = 33). Sleep was evaluated by polysomnography (PSG) during two consecutive in-lab overnight sessions. Non-rapid eye movement (non-REM) sleep stages (stages 1, 2, and slow-wave sleep [SWS]), rapid eye movement (REM) sleep, and wakefulness (Wake) were scored. R-waves were detected automatically in the electrocardiographic (ECG) signal. An all-night heart rate variability analysis was conducted in the ECG signal, with several time- and frequency-domain measures calculated for each sleep–wake stage. Sleep time was divided into thirds (T1, T2, T3). The analysis was performed using a mixed-effects linear regression model. ResultsSleep organization was comparable except for reduced REM sleep percentage in the OW group (p < 0.04). Shorter R–R intervals were found for all sleep stages in the OW group; time-domain measured standard deviation of all R–R intervals (RRSD) was lower during stage 2, SWS and REM sleep (all p < 0.05). The square root of the mean of the sum of the squares of differences between adjacent R–R intervals (RMSSD) was also lower only during wake after sleep onset (WASO) in T1 and T3 (p < 0.05). The OW group had increased very low- and low-frequency (LF) power during WASO (in T1 and T2), and LF power during stage 2 and REM sleep (in T2). During WASO in the OW group, high-frequency (HF) power was lower (in T1 and T2), and LF/HF ratio was higher (in T2, p < 0.007). ConclusionsSeveral sleep-stage-dependent changes in cardiac autonomic regulation characterized the OW group. As sleep-related ANS balance was disturbed in the absence of concomitant metabolic alterations in this sample of otherwise healthy OW adolescents, their relevance for pediatric obesity should be further explored throughout development.

Hypocretin in median raphe nucleus modulates footshock stimuli-induced REM sleep alteration

Stress is one of major factors that cause sleep problems. Hypocretin represents a stress-related neuropeptide and is well known in maintaining physiological wakefulness. The hypocretinergic neurons originate in the lateral hypothalamic area (LHA) and transmit to several brain regions, including the median raphe nuclei (MRNs). The MRNs modulate both fear responses and sleep-wake activity; however, it remains unclear whether stress alters the levels of hypocretin to regulate MRNs and consequently disrupt sleep. In this paper, we employed the inescapable footshock stimuli (IFS) as a stressor and hypothesized that the IFS-induced sleep disruption is mediated by increased hypocretins in the MRNs. Our results demonstrate that the concentrations of hypocretin in the hypothalamus increased after IFS. Rapid eye movement (REM) sleep was reduced after footshock, and microinjection of non-selective hypocretin receptor antagonist TCS-1102 into the MRNs blocked the IFS-induced decrease of REM sleep. Furthermore, administration of hypocretins into the MRNs mimicked the IFS-induced REM sleep reduction. These results conclude that the increased levels of hypocretins in the MRNs mediate the IFS-induced REM sleep reduction.

Why REM Sleep is Reduced in Aquatic and Semi-aquatic Mammals? A Discussion of the Possible Theories

Although most mammals experience rapid eye movement (REM) sleep, the primary function of REM sleep is still debatable. Current data show that aquatic mammals have absent or reduced REM sleep and that semi-aquatic mammals have reduced REM sleep when in water. A few theories have been proposed to explain this reduction in REM sleep in aquatic mammals. Some investigators proposed that seals’ switch from bilateral to uni-hemispheric non-REM sleep in water may render REM sleep unnecessary, and suggested that REM may serve to reverse the brain cooling that occurs in bilateral non-REM sleep. Another proposed theory is the effect of gravity on REM sleep and that aquatic and semi-aquatic species do not need REM sleep in low weightless environments due to the effect of gravity on sleep. In this viewpoint, we critically review a few proposed theories and their supporting evidence.

The relationship between anxiety, depression, daytime sleepiness in the REM-related mild OSAS and the NREM-related mild OSAS.

Obstructive sleep apnea syndrome (OSAS) is a common form of sleep-related respiratory disease characterized by recurrent blockages in the upper airway. Rapid eye movement (REM)-related OSAS is a condition in which apneas and hypopneas are more common during REM sleep. We investigated whether there was any difference between REM-related mild OSAS group and NREM-related mild OSAS group in terms of anxiety, depression, and daytime sleepiness. A total of 166 patients with mild OSAS (72 patients with REM-related and 94 NREM-related OSAS) participated in the study. Hospital Anxiety-Depression Scale (HADS) and Epworth Sleepiness Scale (ESS) questionnaires were completed by both groups. Anxiety and depression scores were significantly higher in patients with REM-related OSAS in comparison to the NREM-related OSAS group (p = 0.01, p = 0.02 respectively). There was no statistically significant difference between the two groups in terms of ESS scores (p = 0.60). The results of our study suggest that patients with REM-related OSAS have higher rates of depression and anxiety compared to non-REM-related OSAS patients and this may adversely affect quality of life. It may be possible to prevent psychiatric complications, such as depression and anxiety, by administering treatments that reduce REM sleep duration and intensity in patients with REM-related OSAS.

Influence of rapid eye movement sleep on all-cause mortality: a community-based cohort study.

Introduction: Although the proportion and duration of rapid eye movement (REM) sleep are correlated with neurological and cardiovascular diseases, whether REM sleep is associated with all-cause mortality in community-based populations remains unknown.Methods: A prospective study was performed within the Sleep Heart Health Study (SHHS, Registration NO. NCT00005275). Total sleep time, sleep efficiency, and REM sleep were measured using polysomnography. Cox proportional hazards regression models were used to estimate the association of the REM sleep with all-cause mortality.Results: Over a mean follow-up period of 11.0 ± 3.1 y, 1234 individuals (21.9%) died. In the entire population, reduced REM sleep was significantly associated with increasing all-cause mortality. After adjustment for age, sex, race, body mass index, smoking status, total cholesterol, triglycerides, high-density lipoprotein, history of diabetes and hypertension, and the apnea–hypopnea index, the duration and proportion of REM sleep were found to be significantly associated with all-cause mortality when the lowest and the highest REM quartile groups were compared (hazard ratio, 95% confidence interval: 1.727, 1.434-2.079; 1.545, 1.298-1.839; respectively).Conclusion: The proportion and duration of REM sleep are negatively associated with all-cause mortality. This finding emphasizes the importance of personalized sleep management in community-based populations.

Association between REM sleep and obstructive sleep apnea in obese and overweight adolescents.

Overweight and obese children have demonstrated reduced rapid eye movement (REM) sleep, affecting energy balance regulation and predisposition to weight gain. Obstructive sleep apnea (OSA) is a known cause of decreased REM sleep. The purpose of this study is to examine the association between the percentage of REM sleep, BMI z-score, and OSA severity in overweight and obese adolescents. We performed a cross-sectional study of 92 (43% female) overweight and obese adolescents (13-17years old) who underwent overnight polysomnography (PSG) at Children's Hospital Los Angeles between 2010 and 2017. The average Body Mass Index (BMI) z-score was 2.27 ± 0.47, with 71% having BMI z-score ≥ 2. REM% during PSG was 15.6 ± 6.8, and obstructive apnea-hypopnea index was 17.1 ± 24.3. The distribution across categories of OSA severity was 27% none (≤ 1.5events/h), 24% mild (> 1.5-5events/h), 8% moderate (> 5-10events/h), and 41% severe (> 10events/h). REM% was not associated with BMI z-score, either on univariate or multivariate regression with adjustment for age, gender, and apnea-hypopnea index (AHI). When subdivided into OSA categories, a 1-unit increase in BMI z-score was associated with a 5.96 (p = 0.03) increase in REM% in mild OSA and an 8.86 (p = 0.02) decrease in REM% in severe OSA. There was no association between BMI z-score and REM% in none and moderate OSA. Among overweight and obese adolescents, BMI z-score was associated with decreased REM% in severe OSA and unexpectedly increased REM% in mild OSA, but there was no association in none or moderate OSA.