Effects Of REM Sleep Deprivation Research Articles

Synaptophysin and GSK-3beta activity in the prefrontal cortex may underlie the effects of REM sleep deprivation and lithium on behavioral functions and memory performance in male rats

Rapid-eye movement (REM) stage of sleep serves a critical role in processing cognitive and behavioral functions. Evidence shows that REM sleep deprivation (REM SD) strongly affects the mood state and cognitive abilities. However, there are many inconsistent reports. Although the exact molecular mechanisms underlying REM SD effects have not well been discovered, however, molecular factors including those affected synaptic plasticity and mood state may be involved. There are two important molecular factors that have not been well studied: synaptophysin and glycogen synthase kinase-3 beta (GSK-3beta). The present study aimed to investigate the role of synaptophysin and GSK-3beta in the modulation of memory and behavioral changes induced by REM SD and lithium (as a potent GSK-3beta inhibitor and mood stabilizer). Multiple platform apparatus was used to induce REM SD for 48 h. Lithium was injected at the dose of 50 mg/kg, intraperitoneal (i.p.). Locomotor activity, anxiety-like behavior, pain threshold, novel object recognition memory, and synaptophysin and GSK-3beta level in the prefrontal cortex were evaluated. Results showed REM SD increased locomotor activity, decreased pain threshold, impaired novel object recognition memory, decreased synaptophysin and increased GSK-3beta levels. Lithium reversed these effects. Anxiety-like behavior was unaffected. For the first time, the present study showed that GSK-3beta and synaptophysin may be involved in the modulation of behavior and cognition induced by REM SD and lithium. In conclusion, we suggested that GSK-3beta upregulation and synaptophysin downregulation may underlie the deleterious effects of REM SD, while lithium may counteract REM SD effects via restoring the level of both.

The impact of REM sleep loss on human brain connectivity

Brain function is vulnerable to the consequences of inadequate sleep, an adverse trend that is increasingly prevalent. The REM sleep phase has been implicated in coordinating various brain structures and is hypothesized to have potential links to brain variability. However, traditional imaging research have encountered challenges in attributing specific brain region activity to REM sleep, remained understudied at the whole-brain connectivity level. Through the spilt-night paradigm, distinct patterns of REM sleep phases were observed among the full-night sleep group (n = 36), the early-night deprivation group (n = 41), and the late-night deprivation group (n = 36). We employed connectome-based predictive modeling (CPM) to delineate the effects of REM sleep deprivation on the functional connectivity of the brain (REM connectome) during its resting state. The REM sleep-brain connectome was characterized by stronger connectivity within the default mode network (DMN) and between the DMN and visual networks, while fewer predictive edges were observed. Notably, connections such as those between the cingulo-opercular network (CON) and the auditory network, as well as between the subcortex and visual networks, also made significant contributions. These findings elucidate the neural signatures of REM sleep loss and reveal common connectivity patterns across individuals, validated at the group level.

The effects of citalopram, SB-334867 and orexin-1, alone or in various combinations, on the anxiogenic-like effects of REM sleep deprivation in male mice.

Sleep deprivation may induce anxiety. On the other hand, anxiety disorders elicit main changes in the quality of sleep. Moreover, orexin and citalopram play a role in the modulation of insomnia and mood diseases. Thus, we planned preclinical research to evaluate the effect of combinations of orexin agents and citalopram on anxiety behavior in rapid eye movement (REM) sleep-deprived mice. For drug intracerebroventricular (i.c.v.) infusion, the guide cannula was surgically implanted in the left lateral ventricle of mice. REM sleep deprivation was conducted via water tank apparatus for 24 h. The anxiety behavior of mice was evaluated using the elevated plus maze (EPM). Our results revealed that REM sleep deprivation reduced the percentage of open arm time (%OAT) and the percentage of the open arm entries (%OAE) but not closed arm entries (locomotor activity) in the EPM test, presenting an anxiogenic response ( P < 0.05). We found a sub-threshold dose of SB-334867, orexin-1 receptor antagonist, and orexin-1 which did not alter anxiety reaction in the REM sleep-deprived mice ( P > 0.05). Intraperitoneal (i.p.) injections of citalopram (5 and 10 mg/kg) increased both %OAT and %OAE ( P < 0.001) representing an anxiolytic effect, but not locomotor activity in the REM sleep-deprived mice. Interestingly, co-treatment of citalopram (1, 5 and 10 mg/kg; i.p.) and SB-334867 (0.1 µg/mouse; i.c.v.) potentiated the anxiolytic effect in the REM sleep-deprived mice. On the other hand, co-treatment of different dosages of citalopram along with a sub-threshold dose of orexin-1 did not alter %OAT, %OAE, and locomotor activity in the REM sleep-deprived mice. We found a synergistic anxiolytic effect of citalopram and SB-334867 in the REM sleep-deprived mice. These results suggested an interaction between citalopram and SB-334867 to prevent anxiogenic behavior in the REM sleep-deprived mice.

Oxidative Stress Induces Endothelial Dysfunction and Endothelial Cell Damage in Rapid Eye Movement (REM) Sleep Deprivation Animal Model

INTRODUCTION: Rapid eye movement (REM) sleep deprivation causes oxidative stress, leading to endothelial dysfunction, a predictor of cardiovascular disease. It is still unclear what causes endothelial dysfunction in patients with sleep disorder. This study evaluates the effects of REM sleep deprivation on the endothelium in the rat model of REM sleep deprivation. MATERIALS AND METHODS: Sprague-Dawley male rats (N=28) were divided into four groups (n=7); (1) free-moving control (FMC), (2) REM sleep deprivation (REMsd), (3) tank control (TC), and (4) sleep recovery (SR). The inverted flowerpot technique was utilised to develop REM sleep deprivation. Bodyweight gain (BWg), food consumption (Fc), and systolic blood pressure (SBP) were evaluated. The descending thoracic aorta was isolated to assess oxidative stress markers, in vitro functional study, and histomorphological examination. RESULTS: REM sleep deprivation showed a decrease in BWg significantly despite a significant increase in Fc, increased SBP, increased oxidative stress markers, caused endothelial dysfunction and endothelial cell damage. In REM sleep-deprived rats, there was a significant reduction in antioxidant markers, including total antioxidant capacity (TAC), superoxide dismutase (SOD) activity, catalase (CAT), and glutathione (GSH), while the levels of malondialdehyde (MDA) were significantly increased. The REM sleep-deprived rats displayed altered vascular function, including impaired vasorelaxation and hypercontractility. Histomorphology of the endothelium in REM sleep-deprived rats revealed features of endothelial damage. CONCLUSION: REM sleep deprivation is suggested to be linked to endothelial dysfunction due to endothelial damage. These changes are proposed to result from increased oxidative stress. Sleep recovery reduced the harmful effects following REM sleep deprivation.

Rapid Eye Movement Sleep Deprivation Combined With Fluoxetine Protects Against Depression-Induced Damage and Apoptosis in Rat Hippocampi via A1 Adenosine Receptor.

Background: Rapid eye movement sleep deprivation (REMSD) and fluoxetine affect depression, yet the detailed molecular mechanisms were not clear.Methods: Rat depression chronic unpredictable stress was constructed, and the body weight of rats was measured. The efficacy of REMSD and fluoxetine on the pleasure experience, exploration, and cognition of rats with depression was determined by the Sucrose preference test, the open field test, and Morris water task, respectively. The effects of REMSD and fluoxetine on depression-induced damage and apoptosis in rat hippocampi were detected using hematoxylin–eosin staining and terminal transferase-mediated biotin 2′-deoxyuridine, 5′-triphosphate nick end labeling. A1 adenosine receptor content was measured by immunohistochemistry. Relative expressions of the A1 adenosine receptor, proteins related to apoptosis (B Bcl-2-associated X protein; B-cell lymphoma 2), phosphoinositide 3-kinase, P38 mitogen-activated protein kinase, cFos, and adenosine deaminase RNA specific two were quantified by quantitative real-time polymerase chain reaction and Western blot as needed.Results: Depression decreased rat weight. REMSD combined with fluoxetine increased body weight, prompted rat behavior, alleviated depression-induced damage, attenuated apoptosis, and promoted A1 adenosine receptor level in rat hippocampi. Furthermore, the combined therapy upregulated expressions of A1 adenosine receptor, B-cell lymphoma 2, and phosphoinositide 3-kinase but downregulated those of B-cell lymphoma 2-associated X protein, P38 mitogen-activated protein kinase, cFos, and adenosine deaminase RNA specific 2 in the hippocampi of rats with depression.Conclusion:REMSD combined with fluoxetine protected rats against depression-induced damage and apoptosis in the hippocampus via the A1 adenosine receptor, providing a possible treatment strategy for depression.

Electrophysiological and neurochemical evaluation of the adverse effects of REM sleep deprivation and epileptic seizures on rat's brain

AimThe current study aims to investigate the impact of paradoxical (REM) sleep deprivation and/or epileptic seizures on rat's cortical brain tissues. Main methodsAnimals were divided into four groups; control, epileptic, REM sleep deprived and epileptic subjected to REM sleep deprivation. Electrocorticogram (ECoG) signals were recorded and quantitatively analyzed for each group. Concentrations of amino acid neurotransmitters; proinflammatory cytokines; and oxidative stress parameters; and acetylcholinesterase activity were determined in the cortex of the animals in different groups. Key findingsResults showed significant variations in the spectral distribution of ECoG waves in the epilepsy model, 24- and 48-hours of REM sleep deprivation and their combined effects indicating a state of cortical hyperexcitability. Significant increases in NO and taurine and significant decrement in glutamine, GABA and glycine were determined. In REM sleep deprived rats significant elevation in glutamate, aspartate, glycine and taurine and a significant lowering in GABA were obtained. This was accompanied by significant reduction in AchE and IL-β. In the cortical tissue of epileptic rats deprived from REM sleep significant increases in lipid peroxidation, TNF-α, IL-1β, IL-6 and aspartate and a significant reduction in AchE were observed. SignificanceThe present data indicate that REM sleep deprivation induces an increase in lipid peroxidation and storming in proinflammatory cytokines in the cortex of rat model of epilepsy during SRS. These changes are associated with a decreased seizure threshold as inferred from the increase in alpha and Beta waves and a decrease in Delta waves of ECoG.

Impact of REM sleep deprivation and sleep recovery on circulatory neuroinflammatory markers.

ObjectivesSleep loss may contribute to neuroinflammation, which might increase neuroinflammatory markers such as neuron-specific enolase (NSE), creatine kinase-brain fraction (CK-BB), lactate dehydrogenase brain fraction (LDH-BB) in blood. Hence, we evaluated the effect of REM sleep deprivation and recovery on these markers.Material and MethodsTwenty-four adult male Sprague Dawley rats were grouped as control, environmental control, REM sleep deprivation, and 24 hour sleep recovery. The rats were sleep deprived for 72 hours and recovered for 24 hours. NSE, CK-BB, and LDH-BB levels in serum were measured using ELISA.ResultsThe serum NSE, CK-BB, and LDH-BB were significantly higher in 72 hour sleep deprived group compared to control (p<0.01). After 24 hours of sleep recovery, the levels of NSE, CK-BB, and LDH-BB were comparable to control (p>0.05).DiscussionREM sleep deprivation increased serum NSE, CK-BB, and LDH-BB, which might be due to neural damage. However, 24 hours of sleep recovery restored these markers.

Investigation of the effect of REM sleep deprivation on epileptic seizures caused by pentylenetetrazole in mice

Aim: To investigate whether different periods of rapid eye movement sleep deprivation (REM SD) contribute to seizure susceptibility, hippocampal oxidative status and balance of inhibition-excitation in the acute epilepsy model. Methods: REM SD was performed using the modified multiple platforms method on adult male BALB/c mice. Pentylentetrazol (PTZ) was injected to induce seizures and hippocampal total antioxidant status (TAS), total oxidant status (TOS), gamma aminobutyric acid (GABA), and glutamate levels were measured using the ELISA method. Results: PTZ-induced seizures following 8 h and 72 h REM SD significantly reduced the hippocampal TAS levels, but did not affect the TOS levels. In REM SD groups, especially after 8 hours of REM sleep loss, there was a significant increase in glutamate in PTZ induction. The hippocampal GABA levels were increased by PTZ-induced seizures after 72 h REM SD. PTZ- induction after 8 hours of RAM SD leads to a significant increase in the seizure duration. Conclusion: It can be speculated that the REM SD can contribute to seizure susceptibility by changing the oxidant-antioxidant balance and excitatory and inhibitory tone in the hippocampus.

Lipid peroxidation in the descending thoracic aorta of rats deprived of REM sleep using the inverted flowerpot technique.

What is the central question of this study? Deprivation of rapid eye movement (REM) sleep is associated with increased oxidative stress, but its effects on the blood vessels are poorly documented. We investigated whether REM sleep deprivation induces oxidative stress and causes lipid peroxidation in the aorta. What is the main finding and its important? We demonstrate that REM sleep deprivation induces oxidative stress and mediates lipid peroxidation in the aorta. This can cause endothelial changes and increased blood pressure. These findings will contribute to the growing body of literature on the mechanism underlying the effects of sleep deprivation on cardiovascular disease. Oxidative stress-mediated lipid peroxidation is a known cause of endothelial injury or dysfunction. Deprivation of rapid eye movement (REM) sleep is associated with oxidative stress. To date, the pathogenesis of increased blood pressure after sleep deprivation remains poorly understood, particularly in the REM sleep phase. Our aim was to investigate the effects of REM sleep deprivation on blood vessels in the REM sleep-deprived rat model. Twenty-eight male Sprague-Dawley rats were divided into four equal groups: free-moving control rats, rats deprived of REM sleep for 72h (REMsd), tank control rats and 72h sleep-recovered rats after 72h of REM sleep deprivation. The rats were deprived of REM sleep using the inverted flowerpot technique. Food consumption, body weight gain and systolic blood pressure were monitored. At the end of the experiment, the descending thoracic aorta was isolated for the measurement of oxidative stress markers. Despite a significant increase in food consumption in the REMsd group compared with the other groups, there was a significant reduction in body weight gain. Systolic blood pressure also showed a significant increase in the REMsd group compared with the other groups. Superoxide dismutase activity was significantly lower and malondialdehyde concentrations significantly higher in the REMsd group compared with the other groups. Increased levels of malondialdehyde are suggestive of lipid peroxidation in the blood vessels, and oxidative stress may be attributed to the initiation of the process. The changes after REM sleep deprivation revert during sleep recovery. In conclusion, the findings of the present study provide convincing evidence that REM sleep deprivation induced lipid peroxidation, leading to endothelial damage.

Lithium acts to modulate abnormalities at behavioral, cellular, and molecular levels in sleep deprivation-induced mania-like behavior.

Ample amount of data suggests role of rapid eye movement (REM) sleep deprivation as the cause and effect of mania. Studies have also suggested disrupted circadian rhythms contributing to the pathophysiology of mood disorders, including bipolar disorder. However, studies pertaining to circadian genes and effect of lithium treatment on clock genes are scant. Thus, we wanted to determine the effects of REM sleep deprivation on expression of core clock genes and determine whether epigenetics is involved. Next, we wanted to explore ultrastructural abnormalities in the hippocampus. Moreover, we were interested to determine oxidative stress, tumor necrosis factor-α (TNF-α), and brain-derived neurotrophic factor levels in the central and peripheral systems. Rats were sleep deprived by the flower pot method and were then analyzed for various behaviors and biochemical tests. Lithium was supplemented in diet. We found that REM sleep deprivation resulted in hyperactivity, reduction in anxiety-like behavior, and abnormal dyadic social interaction. Some of these behaviors were sensitive to lithium. REM sleep deprivation also altered circadian gene expression and caused significant imbalance between histone acetyl transferase/histone deacetylase (HAT/HDAC) activity. Ultrastructural analysis revealed various cellular abnormalities. Lipid peroxidation and increased TNF-α levels suggested oxidative stress and ongoing inflammation. Circadian clock genes were differentially modulated with lithium treatment and HAT/HDAC imbalance was partially prevented. Moreover, lithium treatment prevented myelin fragmentation, disrupted vasculature, necrosis, inflammation, and lipid peroxidation, and partially prevented mitochondrial damage and apoptosis. Taken together, these results suggest plethora of abnormalities in the brain following REM sleep deprivation, many of these changes in the brain may be target of lithium's mechanism of action.

The Effect of REM Sleep Deprivation on mTOR Signaling-Induced by Severe Physical Exercise

: Previous studies indicated that intensity level might be a determining factor in the beneficial or adverse effects of exercise on spatial memory. As intensive exercise appears to deteriorate learning and memory and recent reports have suggested that one-night sleep deprivation improves mood and neurogenesis in depressed patients for at least one day. The present study was designed to investigate the effect of REM sleep deprivation (REM-SD) on memory impairment induced by intense exercise. Animals had undergone an intense protocol (speed: 18 m/min and no tilt for the first week, the duration and treadmill tilt were increased progressively, 10 minutes and five degrees increased in each week) of treadmill for five days a week for five weeks then deprived of sleep for 24 hours using the water-filled multiple platforms. The level of mammalian Target of Rapamycin (mTOR) in the hippocampus and the prefrontal cortex (PFC) was assessed by Western blotting. Five weeks of intensive exercise and 24h REM-SD were decreased the level of mTOR expression; 24h REM-SD improved intensive exercise-associated decreases in the basal levels of mTOR. The present data suggested that REM-SD might be considered as a compensatory factor for a short time. In addition, increasing in the mTOR level could improve memory impairment-induced by intensive exercise.

Morin hydrate mitigates rapid eye movement sleep deprivation-induced neurobehavioural impairments and loss of viable neurons in the hippocampus of mice

Rapid eye movement sleep deprivation distorts the body’s homeostasis and results in oxidative breakdown which may be responsible for a variety of neurological disorders. Some naturally occurring compounds of plant origin with antioxidant and neuroprotective properties are known to attenuate the detrimental effects of REM sleep deprivation. Morin hydrate, a flavonoid from Mulberry has demonstrated antioxidant and neuroprotective activities but its effect in sleep disturbed mice is unknown. The study was designed to explore the neuroprotective effect of Morin hydrate on 48 h. REM sleep deprivation-induced behavioural impairments and neuronal damage in mice.Mice were allotted into six treatment groups (n = 6): groups 1 and 2 received vehicle (10 ml/kg normal saline), groups 3–5 received Morin hydrate (5, 10, 20 mg/kg i.p) while group 6 received ginseng (25 mg/kg) which served as the reference drug. Treatment was performed daily for 5 days and animals were sleep-deprived on the last 48 h. Various behavioural tests (Elevated plus maze, Y-maze, locomotor activity) followed by oxidative parameters (malondialdehyde, nitric oxide, reduced glutathione) and histolopathological changes in the Cornu ammonis 1 (CA1) region of the hippocampus were assessed. Data were analysed using ANOVA at α0.05.Morin hydrate (5, 10, 20 mg/kg) significantly enhanced memory performance, improves anxiolytic-like behaviour, reverses hyperlocomotion, restored depleted reduced glutathione, attenuated raised malondialdehyde and nitric oxide levels as compared to control animals and protects against loss of hippocampal neurons.Results of this present study suggest that Morin hydrate possess neuroprotective effects against sleep deprivation-induced behavioural impairments, oxidative stress and neuronal damage.

REM sleep deprivation induces endothelial dysfunction and hypertension in middle-aged rats: Roles of the eNOS/NO/cGMP pathway and supplementation with L-arginine.

Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes. The results showed that REM sleep deprivation decreased body weight, increased blood pressure, and impaired endothelial function of the aortas in middle-aged rats but not young rats. Moreover, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) concentrations as well as endothelial NO synthase (eNOS) phosphorylation in the aorta were decreased by REM sleep deprivation. Supplementation with L-arginine could protect against REM sleep deprivation-induced hypertension, endothelial dysfunction, and damage to the eNOS/NO/cGMP signaling pathway. The results of the present study suggested that REM sleep deprivation caused endothelial dysfunction and hypertension in middle-aged rats via the eNOS/NO/cGMP pathway and that these pathological changes could be inhibited via L-arginine supplementation. The present study provides a new strategy to inhibit the signaling pathways involved in insomnia-induced or insomnia-enhanced cardiovascular diseases.

Electronic Sleep Stage Classifiers: A Survey and VLSI Design Methodology.

First, existing sleep stage classifier sensors and algorithms are reviewed and compared in terms of classification accuracy, level of automation, implementation complexity, invasiveness, and targeted application. Next, the implementation of a miniature microsystem for low-latency automatic sleep stage classification in rodents is presented. The classification algorithm uses one EMG (electromyogram) and two EEG (electroencephalogram) signals as inputs in order to detect REM (rapid eye movement) sleep, and is optimized for low complexity and low power consumption. It is implemented in an on-board low-power FPGA connected to a multi-channel neural recording IC, to achieve low-latency (order of 1 ms or less) classification. Off-line experimental results using pre-recorded signals from nine mice show REM detection sensitivity and specificity of 81.69% and 93.86%, respectively, with the maximum latency of 39 [Formula: see text]. The device is designed to be used in a non-disruptive closed-loop REM sleep suppression microsystem, for future studies of the effects of REM sleep deprivation on memory consolidation.

REM sleep deprivation induces changes of down regulatory antagonist modulator (DREAM) expression in the ventrobasal thalamic nuclei of sprague-dawley rats.

REM sleep is a crucial component of sleep. Animal studies indicate that rapid eye movement (REM) sleep deprivation elicits changes in gene expression. Down regulatory antagonist modulator (DREAM) is a protein which downregulates other gene transcriptions by binding to the downstream response element site. The aim of this study is to examine the effect of REM sleep deprivation on DREAM expression in ventrobasal thalamic nuclei (VB) of rats. Seventy-two male Sprague-Dawley rats were divided into four major groups consisting of free-moving control rats (FMC) (n = 18), 72-h REM sleep-deprived rats (REMsd) (n = 18), 72-h REM sleep-deprived rats with 72-h sleep recovery (RG) (n = 18), and tank control rats (TC) (n = 18). REM sleep deprivation was elicited using the inverted flower pot technique. DREAM expression was examined in VB by immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) studies. The DREAM-positive neuronal cells (DPN) were decreased bilaterally in the VB of rats deprived of REM sleep as well as after sleep recovery. The nuclear DREAM extractions were increased bilaterally in animals deprived of REM sleep. The DREAM messenger RNA (mRNA) levels were decreased after sleep recovery. The results demonstrated a link between DREAM expression and REM sleep deprivation as well as sleep recovery which may indicate potential involvement of DREAM in REM sleep-induced changes in gene expression, specifically in nociceptive processing.

Effects of REM sleep deprivation on sensorimotor gating and startle habituation in rats: Role of social isolation in early development

The present study examined the role of rapid eye movement (REM) sleep on sensorimotor gating function in a developmentally rodent model of schizophrenic-spectrum disorders. Startle magnitude, prepulse inhibition (PPI) and startle habituation in an acoustic startle test were measured after 72-h of REM sleep deprivation (REMSD) in 14-week-old rats that were reared in one of the following conditions: control social interaction, 2-week isolation, and continuous isolation, since weaning. The results showed that REMSD significantly inhibited rats’ PPI in socially controlled rats, and rats in two isolation groups appeared less sensitive to REMSD. After REMSD, startle habituation was significantly reduced in continuous-isolated rats but not in 2-week-isolated rats. These data indicate that REM sleep is essential for PPI; REMSD inhibits startle habituation in rats with continuous social isolation. In addition, social interaction, in early life or for the whole life, functions differently to the sensorimotor gating.

Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation

Selective rapid eye movement sleep (REMS) deprivation using the platform-on-water ("flower pot") method causes sleep rebound with increased REMS, decreased REMS latency, and activation of the melanin-concentrating hormone (MCH) expressing neurons in the hypothalamus. MCH is implicated in the pathomechanism of depression regarding its influence on mood, feeding behavior, and REMS. We investigated the effects of the most selective serotonin reuptake inhibitor escitalopram on sleep rebound following REMS deprivation and, in parallel, on the activation of MCH-containing neurons. Escitalopram or vehicle (10 mg/kg, intraperitoneally) was administered to REMS-deprived (72 h) or home cage male Wistar rats. During the 3-h-long "rebound sleep", electroencephalography was recorded, followed by an MCH/Fos double immunohistochemistry. During REMS rebound, the time spent in REMS and the number of MCH/Fos double-labeled neurons in the lateral hypothalamus increased markedly, and REMS latency showed a significant decrease. All these effects of REMS deprivation were significantly attenuated by escitalopram treatment. Besides the REMS-suppressing effects, escitalopram caused an increase in amount of and decrease in latency of slow wave sleep during the rebound. These results show that despite the high REMS pressure caused by REMS deprivation procedure, escitalopram has the ability to suppress REMS rebound, as well as to diminish the activation of MCH-containing neurons, in parallel. Escitalopram caused a shift from REMS to slow wave sleep during the rebound. Furthermore, these data point to the potential connection between the serotonergic system and MCH in sleep regulation, which can be relevant in depression and in other mood disorders.

Increased cortical excitability after selective REM sleep deprivation in healthy humans: A transcranial magnetic stimulation study

REM sleep has antiepileptogenic properties whereas, its loss is known to have a proconvulsive role. However, the mechanisms underlying the proepileptogenic effects of REM sleep deprivation are yet not fully understood. The aim of our study was to evaluate the effects of selective REM sleep deprivation (SRD) on cortical excitability in healthy subjects by means of transcranial magnetic stimulation (TMS). Ten normal subjects underwent three TMS sessions: (1) in baseline condition (BL), (2) after SRD by awakening them at each REM sleep onset and (3) after non-rapid eye movement sleep awakenings (NREM-A) as control for potential non-specific effects of interruptions. The TMS investigation included two protocols: (a) the evaluation of motor evoked potentials (MEPs) and silent period (SP) parameters, recorded in response to single pulse magnetic stimulation; (b) the evaluation of the time course of intracortical motor activity tested with paired-pulse TMS applied at inter-stimulus intervals of 1-10 ms. After SRD the principal finding observed using single pulse TMS was a significant reduction in the duration of SP whereas, a reduction of intracortical inhibition was found, using the paired-pulse TMS. TMS parameters did not show significant changes after NREM-A with respect to BL. SRD may influence cortical excitability with a reduction of inhibitory intracortical mechanisms, thus supporting the proconvulsant role of REM loss.

Effect of REM sleep deprivation on the antioxidant status in the brain of Wistar rats.

Rapid eye movement [REM] sleep deprivation is a stressor. It results in a predictable syndrome of physiological changes in rats. It has been proposed that reactive oxygen species and the resulting oxidative stress may be responsible for some of the effects of sleep deprivation. The present study was undertaken to investigate the reversible nature of the effects of 96 hours of REM sleep deprivation on lipid peroxidation and total reduced glutathione level in the hypothalamus, midbrain and hindbrain of Wistar strain rats. The rats were deprived of REM sleep using the inverted flowerpot technique. All the animals were maintained in standard animal house condition with 12-h light and 12-h dark cycles. At the end of the stipulated time Jugular venous blood sample of 2 ml was collected under mild ether anesthesia for the assay of stress index, plasma corticosterone. Lipid peroxidation using thiobarbituric acid, total reduced glutathione using DTNB (GSH) were assayed in the brain regions dissected out. This study showed that 96 hours of REM sleep deprivation results in increased lipid peroxidation and reduction in total reduced glutathione level in the discrete regions of brain studied. However following restorative sleep for 24 hours all the changes reverts back to base line value. This study shows that oxidative stress produced by 96 hours of REM sleep deprivation is reversible. From this study it is clear that, REM sleep deprivation is a potent oxidative stressor. This could probably play a role in the behavioral and performance alteration seen in both experimental animals as well as humans following REM sleep deprivation. Further investigations in this line are needed to highlight the importance of REM sleep.

Rapid eye movement sleep deprivation modulates synapsinI expression in rat brain

Rapid eye movement sleep (REMS) deprivation (REMSD) has been reported to elevate neurotransmitter level in the brain; however, intracellular mechanism of its increased release was not studied. Phosphorylation of synapsinI, a synaptic vesicle-associated protein, is involved in the regulation of neurotransmitter release. In this study, rats were REMS deprived by classical flowerpot method; free moving control (FMC), large platform control (LPC) and recovery control (REC) was carried out. In another set REMS deprived rats were intraperitoneally (i.p.) injected with α1-adrenoceptor antagonist, prazosin (PRZ). Effects of REMSD on Na-K ATPase activity and on the total synapsinI as well as phosphorylated synapsinI levels were estimated in synaptosomes prepared from whole brain. It was observed that REMSD significantly increased synaptosomal Na-K ATPase activity, which was prevented by PRZ. Western blotting of the same samples by anti-synapsinI and anti-synapsinI-phosphoSer603 showed that REMSD increased both the total as well as phospho-form of synapsinI as compared to respective levels in FMC and LPC samples. These findings suggest a functional link between REMSD and synaptic vesicular mobilization at the presynaptic terminal, a process that is essential for neurotransmitter release. The findings help explaining the intracellular mechanism of elevated neurotransmitter release associated to REMSD.