REM Sleep Deprivation In Rats Research Articles

Spinal bestrophin-1 and anoctamin-1 channels have a pronociceptive role in the tactile allodynia induced by REM sleep deprivation in rats

Bestrophin-1 and anoctamin-1 are members of the calcium-activated chloride channels (CaCCs) family and are involved in inflammatory and neuropathic pain. However, their role in pain hypersensitivity induced by REM sleep deprivation (REMSD) has not been studied. This study aimed to determine if anoctamin-1 and bestrophin-1 are involved in the pain hypersensitivity induced by REMSD. We used the multiple-platform method to induce REMSD. REM sleep deprivation for 48 h induced tactile allodynia and a transient increase in corticosterone concentration at the beginning of the protocol (12 h) in female and male rats. REMSD enhanced c-Fos and α2δ-1 protein expression but did not change activating transcription factor 3 (ATF3) and KCC2 expression in dorsal root ganglia and dorsal spinal cord. Intrathecal injection of CaCCinh-A01, a non-selective bestrophin-1 blocker, and T16Ainh-A01, a specific anoctamin-1 blocker, reverted REMSD-induced tactile allodynia. However, T16Ainh-A01 had a higher antiallodynic effect in male than female rats. In addition, REMSD increased bestrophin-1 protein expression in DRG but not in DSC in male and female rats. In marked contrast, REMSD decreased anoctamin-1 protein expression in DSC but not in DRG, only in female rats. Bestrophin-1 and anoctamin-1 promote pain and maintain tactile allodynia induced by REM sleep deprivation in both male and female rats, but their expression patterns differ between the sexes.

Cognitive Enhancing Activities of Coenzyme Q10, Ramipril, and Vinpocetine Through Modulating Neuroinflammatory Response and Oxidative Damage Inflicted by Acute REM Sleep Deprivation in Rats

Sleep plays a vital role to help in normal biological functions that are required for normal cognitive functioning. This study was done to determine the cognition-modulating effects of coenzyme Q10 (CoQ10), ramipril, and vinpocetine on REM sleep-deprived acute insomniac rat models. A total of Forty-eight albino rats were divided into eight groups (Gr) (n=6).). Gr. 1 was REM control and Gr. 2 was REM sleep-deprived rats treated with water. Gr. 3 to Gr.8 - REM sleep-deprived rats were administered corn oil, donepezil, vinpocetine, coenzyme Q10+corn oil, ramipril, and (coenzyme Q10 + corn oil + ramipril) respectively. Except for the control Gr 1, REM sleep deprivation was induced in Gr. 2 and 8 daily for 7 days. All the rats were subjected to a Morris water maze (MWM) to test the navigation memory dysfunction after 7 days of acute insomnia. The rats were deprived of REM sleep by using a modified multiple platform method. The body weight of the animals was measured on day 1 and day 7. On day 1 and Day 2 acquisition trials, all groups of rats showed comparable latency time required to reach the hidden platform. However, on day 3 and Day 4, rats treated with coenzyme Q10, ramipril, and the combination (CoQ10+ Ramipril) showed a significant decrease in latency time (p<0.01). In the probe trial, sleep-deprived rats showed a significant decrease (p<0.001) in the percentage of time spent in the target quadrant as compared to the REM control. However, there was a significant increase in the percentage time spent in CoQ10, ramipril, the combination (CoQ10+ ramipril), donepezil, and vinpocetine as compared to sleep-deprived rats (p<0.05). At the end of day 7 of insomnia, when the body weight of rats was compared with day 1, there was a significant decrease in weight gain was seen with the sleep-deprived rats treated with corn oil, ramipril, vinpocetine, CoQ10, and (CoQ10+ramipril) (p<0.05). The present study shows that coenzyme Q10, ramipril, and their combination improve sleep deprivation induced cognition impairment.

Dexmedetomidine prevents spatial learning and memory impairment induced by chronic REM sleep deprivation in rats.

The online version contains supplementary material available at 10.1007/s41105-023-00450-8.

Gastrodin Improves Cognitive Dysfunction in REM Sleep-Deprived Rats by Regulating TLR4/NF-κB and Wnt/β-Catenin Signaling Pathways

Gastrodin is the active ingredient in Gastrodia elata. Our previous studies demonstrated that gastrodin ameliorated cerebral ischemia-reperfusion and hypoperfusion injury and improved cognitive deficit in Alzheimer's disease. This study aims to examine the effects of gastrodin on REM sleep deprivation in rats. Gastrodin (100 and 150 mg/kg) was orally administered for 7 consecutive days before REM sleep deprivation. Seventy-two hours later, pentobarbital-induced sleep tests and a Morris water maze were performed to measure REM sleep quality and learning and memory ability. Histopathology was observed with hematoxylin-eosin staining, and the expression of the NF-κB and Wnt/β-catenin signaling pathways was examined using Western blot. After REM sleep deprivation, sleep latency increased and sleep duration decreased, and the ability of learning and memory was impaired. Neurons in the hippocampal CA1 region and the cortex were damaged. Gastrodin treatment significantly improved REM sleep-deprivation-induced sleep disturbance, cognitive deficits and neuron damage in the hippocampus CA1 region and cerebral cortex. A mechanism analysis revealed that the NF-κB pathway was activated and the Wnt/β-catenin pathway was inhibited after REM sleep deprivation, and gastrodin ameliorated these aberrant changes. Gastrodin improves REM sleep-deprivation-induced sleep disturbance and cognitive dysfunction by regulating the TLR4/NF-κB and Wnt/β-catenin signaling pathways and can be considered a potential candidate for the treatment of REM sleep deprivation.

Rapid Eye Movement sleep deprivation of rat generates ROS in the hepatocytes and makes them more susceptible to oxidative stress.

BackgroundRapid Eye Movement sleep deprivation (REMSD) of rats causes inflammation of the liver and apoptotic cell death of neurons and hepatocytes. Studies also suggest that REM sleep deprivation can cause muscle as well as cardiac injury and neurodegenerative diseases.Objective and methodsThe aim of this research was to determine whether REM sleep deprivation of rats would increase the levels of reactive oxygen species (ROS) in the hepatocytes and create oxidative stress in them. We selectively deprived the rats for REM sleep using the standard flower pot method.ResultsWe observed that when rats were subjected to REM sleep deprivation, the levels of ROS in their hepatocytes increased ~184.33% compared to large platform control (LPC) group by day 9 of deprivation, but it returned towards normal level (~49.27%) after recovery sleep for 5 days. Nitric oxide synthase (iNOS) gene expression and protein levels as determined by real-time PCR and western blot analysis respectively were found to be elevated in hepatocytes of REM sleep deprived rats as compared to the LPC group. The level of nitric oxide (NO) in the hepatocytes of REMSD rats also increased by ~404.40% as compared to the LPC group but sleep recovery for 5 days normalized the effect (~135.35% compared to LPC group). We used a large platform control group as a reference group to compare with the REM sleep deprived group as the effect on the hepatocytes of both LPC group and cage control groups were not significantly different.DiscussionWe have analyzed the oxidative stress generated in the hepatocytes of rats due to REM sleep deprivation and further consequences of it. REMS deprivation not only increased the levels of ROS in the hepatocytes but also induced iNOS and NO in them. REM sleep deprived hepatocytes became more susceptible to oxidative stresses on further exposures. Furthermore, our study has great pathological and physiological.

The role of omega-3 on modulation of cognitive deficiency induced by REM sleep deprivation in rats

Prolonged sleep deprivation causes cognitive deficits. In rats, for instance, sleep deprivation weakens spatial learning and long-term potentiation (LTP). We examined the effects of omega-3 on cognitive deficiency induced by REM sleep deprivation (RSD). For this purpose, we used a fear conditioning paradigm, forced swim test (FST) apparatus, and hot plate test. Intravenously omega-3 injection was performed during 3 consecutive days. Rats trained in the fear conditioning apparatus after 24 h. During conditioning, animals were received foot shocks, either alone or paired with a sound. Sleep deprivation paradigm was carried out in which REM sleep was completely prevented and non-REM sleep was intensely declined for 24 h. Then, context-dependent retention, anxiety behaviors, and hot plate tests were done. Auditory-dependent retention, anxiety behaviors, and FST were carried out 24 h later. 24 h of RSD impaired cognitive function, however intravenously administration of omega-3 improved (0.25, 0.5 and 1 mg/kg) context- or auditory-dependent memory, induced anxiolytic (1 mg/kg), antidepressant (1.25 mg/kg), and anti-nociceptive (0.25 mg/kg) effects. The results revealed that RSD interferes with the neural systems underlying cognitive functions and supports the involvement of omega-3 in the modulation of cognitive functions.

Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats.

A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC), would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD) because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness.

REM sleep deprivation of rats induces acute phase response in liver

REM sleep is essential for maintenance of body physiology and its deprivation is fatal. We observed that the levels of ALT and AST enzymes and pro-inflammatory cytokines like IL-1β, IL-6 and IL-12 circulating in the blood of REM sleep deprived rats increased in proportion to the extent of sleep loss. But in contrast the levels of IFN-γ and a ∼200kDa protein, identified by N-terminal sequencing to be alpha-1-inhibitor-3(A1I3), decreased significantly. Quantitative PCR analysis confirmed that REM sleep deprivation down regulates AII3 gene and up regulates IL1 β, IL6 and their respective receptors gene expression in the liver initiating its inflammation.

Chronic lithium prevents REM sleep deprivation-induced increased responsiveness to apomorphine.

REM sleep deprivation of rats induces an increased responsiveness to dopaminergic agonists. Chronic lithium (Li) has been reported to prevent the development of dopamine receptor supersensitivity induced by other agents. The effects of chronic dietary Li administration (producing a mean serum level of 0.96 mequiv. litre-1) and 96 h REM sleep deprivation were studied. Chronic Li completely blocked the increased stereotypy, and partially prevented the aggressive behaviour induced, respectively, by 0.6 and 5 mg kg-1 of apomorphine in REM sleep deprived rats compared with the appropriate control groups. This study constitutes the first attempt to evaluate chronic lithium effects on rats undergoing REM sleep deprivation, chosen as another method of inducing alteration of dopaminergic sensitivity.

Effects of age on recovery of body weight following REM sleep deprivation of rats

Chronically enforced rapid eye (paradoxical) movement sleep deprivation (REM-SD) of rats leads to a host of pathologies, of which hyperphagia and loss of body weight are among the most readily observed. In recent years, the etiology of many REM-SD-associated pathologies have been elucidated, but one unexplored area is whether age affects outcomes. In this study, male Sprague-Dawley rats at 2, 6, and 12 months of age were REM sleep-deprived with the platform (flowerpot) method for 10–12 days. Two-month-old rats resided on 7-cm platforms, while 10-cm platforms were used for 6- and 12-month-old rats; rats on 15-cm platforms served as tank controls (TCs). Daily changes in food consumption (g/kg 0.67) and body weight (g) during baseline, REM-SD or TCs, and post-experiment recovery in home cages were determined. Compared to TCs, REM-SD resulted in higher food intake and decreases in body weight. When returned to home cages, food intake rapidly declined to baseline levels. Of primary interest was that rates of body weight gain during recovery differed between the age groups. Two-month-old rats rapidly restored body weight to pre-REM-SD mass within 5 days; 6-month-old rats were extrapolated by linear regression to have taken about 10 days, and for 12-month-old rats, the estimate was about 35 days. The observation that restoration of body weight following its loss during REM-SD may be age-dependent is in general agreement with the literature on aging effects on how mammals respond to stress.

Comet Assay to Determine DNA Damage Induced by REM Sleep Deprivation in Rats

Comet Assay to Determine DNA Damage Induced by REM Sleep Deprivation in Rats

Potentiation of metaphit-induced audiogenic seizures by REM sleep deprivation in rats

The possibility that REM sleep deprivation (REMD) induces increased susceptibility of rats to the convulsive effects of metaphit was investigated. Metaphit-induced audiogenic seizures were studied in three groups of animals: 1) caged control; 2) large platform animals; and 3) small platform, REMD animals. After 48 h of confinement to their environments the rats from all three groups were injected with metaphit (10 mg kg −1, IP) and the procedures continued for the next 24 h. Immediately after removal from platforms and at 3-h intervals thereafter all rats were individually subjected to intense sound stimulation. Convulsive responses were recorded and analyzed with respect to incidence, intensity, and duration. The REMD rats were found to be more sensitive to the convulsive effects of metaphit compared to nondeprived rats. This was manifested in significantly shorter latencies to seizures, and significantly higher incidence, severity, and duration of seizures, especially of the most severe seizure component—tonic extensor convulsion. Inducing rats to convulse while they were being REM sleep deprived eliminated the REM sleep rebound observed in REMD rats that did not convulse. The occurrence of spontaneous EEG seizures during the undisturbed recovery period reduced REM sleep rebound. The results demonstrate a reciprocal relation between seizure behavior and REM sleep.

Negative transfer abolished by REM sleep deprivation in rats

Brief deprivation of REM sleep (REMD) immediately following inhibitory avoidance training abolished negative transfer in an active avoidance situation without impairing retention of the inhibitory avoidance response. REMD beginning 3 hr after inhibitory training had no effect. A reminder treatment (brief placement in the apparatus) between 30 min and 24 hr before active avoidance training counteracted the REMD impairment of negative transfer. The reminder treatment was not impaired by subsequent REMD.

PROCEEDINGS OF THE AUSTRALASIAN SOCIETY OF CLINICAL AND EXPERIMENTAL PHARMACOLOGISTS

PROCEEDINGS OF THE AUSTRALASIAN SOCIETY OF CLINICAL AND EXPERIMENTAL PHARMACOLOGISTS