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Background: Chronic Rapid eye movement (REM) sleep deprivation has been associated with various cardiovascular alterations, including disruptions in antioxidant defense mechanisms, lipid metabolism, and inflammatory responses. This study investigates the therapeutic potential of green tea extract (GTE) in mitigating these adverse effects. Methods: A total of 24 male Wistar albino rats were used in this study and divided into the control group (n = 8), Chronic-REM Sleep Deprivation (CRSD) Group (n = 8) and Chronic-REM SD + Green Tea 200 (CRSD + GTE200) Group (n = 8). After 21 days, a comprehensive analysis of paraoxonase (PON1), arylesterase (ARE), malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), proinflammatory cytokines, and lipid profiles in aortic tissue, heart tissue, and serum was conducted in a sleep-deprived rat model. Results: Chronic REM sleep deprivation led to a significant reduction in PON1 and ARE levels in aortic (p = 0.046, p = 0.035 respectively) and heart tissues (p = 0.020, p = 0.019 respectively), indicative of compromised antioxidant defenses. MDA levels increased, and NOx levels decreased, suggesting oxidative stress and impaired vascular function. Lipid profile alterations, including increased triglycerides and total cholesterol, were observed in serum. Elevated levels of inflammatory cytokines (IL-6 and TNF-alpha) further indicated an inflammatory response (p = 0.007, p = 0.018 respectively). GTE administration demonstrated a protective role, restoring antioxidant enzyme levels, suppressing lipid peroxidation, and improving NOx levels. Conclusion: These findings suggest the therapeutic potential of GTE in alleviating the cardiovascular impairments of chronic REM sleep deprivation, emphasizing its candidacy for further clinical exploration as a natural intervention in sleep-related disorders and associated cardiovascular risks. [ABSTRACT FROM AUTHOR]

Rapid eye movement sleep (REMS) maintains brain excitability at least by regulating Na‐K ATPase activity. Although REMS deprivation (REMSD)‐associated elevated noradrenaline (NA) increases Na‐K ATPase protein expression, its mRNA transcription did not increase. We hypothesized and confirmed both in vivo as well as in vitro that elevated mRNA stability explains the apparent puzzle. The mRNA stability was measured in control and REMSD rat brain with or without in vivo treatment with α1‐adrenoceptor (AR) antagonist, prazosin (PRZ). Upon REMSD, Na‐K ATPase α1‐, and α2‐mRNA stability increased significantly, which was prevented by PRZ. To decipher the molecular mechanism of action, we estimated NA‐induced Na‐K ATPase mRNA stability in Neuro‐2a cells under controlled conditions and by transcription blockage using Actinomycin D (Act‐D). NA increased Na‐K ATPase mRNA stability, which was prevented by PRZ and propranolol (PRP, β‐AR antagonist). The knockdown assay confirmed that the increased mRNA stabilization was induced by elevated cytoplasmic abundance of Human antigen R (HuR) and involving (Phospholipase C) PLC‐mediated activation of Protein Kinase C (PKC). Additionally, using cell‐impermeable Enz‐link sulfo NHS‐SS‐Biotin, we observed that NA increased Na‐K ATPase α1‐subunits on the Neuro‐2a cell surface. We conclude that REMSD‐associated elevated NA, acting on α1‐ and β‐AR, increases nucleocytoplasmic translocation of HuR and increases Na‐K ATPase mRNA stability, resulting in increased Na‐K ATPase protein expression. The latter then gets translocated to the neuronal membrane surface involving both PKC and (Protein Kinase A) PKA‐mediated pathways. These findings may be exploited for the amelioration of REMSD‐associated chronic disorders and symptoms. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic Rapid eye movement (REM) sleep deprivation has been associated with various cardiovascular alterations, including disruptions in antioxidant defense mechanisms, lipid metabolism, and inflammatory responses. This study investigates the therapeutic potential of green tea extract (GTE) in mitigating these adverse effects. Methods A total of 24 male Wistar albino rats were used in this study and divided into the control group (n = 8), Chronic-REM Sleep Deprivation (CRSD) Group (n = 8) and Chronic-REM SD + Green Tea 200 (CRSD + GTE200) Group (n = 8). After 21 days, a comprehensive analysis of paraoxonase (PON1), arylesterase (ARE), malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), proinflammatory cytokines, and lipid profiles in aortic tissue, heart tissue, and serum was conducted in a sleep-deprived rat model. Results Chronic REM sleep deprivation led to a significant reduction in PON1 and ARE levels in aortic (p = 0.046, p = 0.035 respectively) and heart tissues (p = 0.020, p = 0.019 respectively), indicative of compromised antioxidant defenses. MDA levels increased, and NOx levels decreased, suggesting oxidative stress and impaired vascular function. Lipid profile alterations, including increased triglycerides and total cholesterol, were observed in serum. Elevated levels of inflammatory cytokines (IL-6 and TNF-alpha) further indicated an inflammatory response (p = 0.007, p = 0.018 respectively). GTE administration demonstrated a protective role, restoring antioxidant enzyme levels, suppressing lipid peroxidation, and improving NOx levels. Conclusion These findings suggest the therapeutic potential of GTE in alleviating the cardiovascular impairments of chronic REM sleep deprivation, emphasizing its candidacy for further clinical exploration as a natural intervention in sleep-related disorders and associated cardiovascular risks.

Background: Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors in rodents. On the other hand, lithium, as one of the oldest drugs used in neuropsychiatric disorders, is still one of the best drugs for the treatment and control of bipolar disorder. In this study, we aimed to investigate the role of chronic short-term REM SD in the induction of manic-like behaviors in female rats. Methods: The rats were exposed to REM SD for 14 days (6 hours/day). Lithium was intraperitoneally injected at the doses of 10, 50, and 100 mg/kg. Results: REM SD induced hyperactivity and OCD-like behavior, and decreased anxiety, depressive-like behavior, and pain subthreshold. REM SD also impaired passive avoidance memory and decreased hippocampal brain-derived neurotrophic factor (BDNF) expression level. Lithium at the doses of 50 and 100 mg/kg partly and completely abolished these effects, respectively. However, lithium (100 mg/kg) increased BDNF expression level in control and sham REM SD rats with no significant changes in behavior. Conclusions: Chronic short-term REM SD may induce a mania-like model and lead to OCD-like behavior and irritability. In the present study, we demonstrated a putative rodent model of mania induced by chronic REM SD in female rats. We suggest that future studies should examine behavioral and mood changes following chronic REM SD in both sexes. Furthermore, the relationship between manic-like behaviors and chronic REM SD should be investigated. [ABSTRACT FROM AUTHOR]

Rationale: Prepulse inhibition (PPI) impairment reflects sensorimotor gating problems, i.e. in schizophrenia. This study aims to enlighten the role of orexinergic regulation on PPI in a psychosis-like model. Objectives: In order to understand the impact of orexinergic innervation on PPI and how it is modulated by age and baseline PPI (bPPI), chronic orexin A (OXA) injections was carried on non-sleep-deprived and sleep-deprived rats that are grouped by their bPPI. Methods: bPPI measurements were carried on male Wistar rats on P45 or P90 followed by grouping into low-PPI and high-PPI rats. The rats were injected with OXA twice per day for four consecutive days starting on P49 or P94, while the control groups received saline injections. 72 h REMSD was carried on via modified multiple platform technique on P94 and either OXA or saline was injected during REMSD. PPI tests were carried out 30 min. after the last injection. Results: Our previous study with acute OXA injection after REMSD without bPPI grouping revealed that low OXA doses might improve REMSD-induced PPI impairment. Our current results present three important conclusions: (1) The effect of OXA on PPI is bPPI-dependent and age-dependent. (2) The effect of REMSD is bPPI-dependent. (3) The effect of OXA on PPI after REMSD also depends on bPPI. Conclusion: Orexinergic regulation of PPI response with and without REMSD can be predicted by bPPI levels. Our findings provide potential insights into the regulation of sensorimotor gating by sleep/wakefulness systems and present potential therapeutic targets for the disorders, where PPI is disturbed. [ABSTRACT FROM AUTHOR]

We aimed to investigate whether antagonism of the cannabinoid CB 1 receptor (CB 1 R) could affect novel object recognition (NOR) memory in chronically rapid eye movement sleep-deprived (RSD) rats. The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique. The CB 1 R antagonist rimonabant (1 or 3 mg/kg, i.p.) was administered either at one hour prior to the sample phase for acquisition, or immediately after the sample phase for consolidation, or at one hour before the test phase for retrieval of NOR memory. For the reconsolidation task, rimonabant was administered immediately after the second sample phase. The RSD episode impaired acquisition, consolidation, and retrieval, but it did not affect the reconsolidation of NOR memory. Rimonabant administration did not affect acquisition, consolidation, and reconsolidation; however, it attenuated impairment of the retrieval of NOR memory induced by chronic RSD. These findings, along with our previous report, would seem to suggest that RSD may affect different phases of recognition memory based on its duration. Importantly, it seems that the CB 1 R may, at least in part, be involved in the adverse effects of chronic RSD on the retrieval, but not in the acquisition, consolidation, and reconsolidation, of NOR memory. [ABSTRACT FROM AUTHOR]

Objective(s): Sleep deprivation is a common health problem in modern society and is negatively associated with deleterious effects on cognitive functions such as learning and memory ability. This study was undertaken to provide a detailed account of the effect of chronic ozone intraperitoneal injection on the deleterious effects of sleep deprivation on brain function in rats. Materials and Methods: Sleep deprivation was induced using the modified multiple platform model. The rats received REM sleep deprivation with an intraperitoneal injection of ozone or midazolam for 28 days. The effects of ozone on REM sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by the following approaches: Morris water maze (MWM) tests were used to evaluate spatial learning and memory of rats. Morphological changes in the brain were evaluated using hematoxylin and eosin (HE) staining. RNA-sequence was performed to seek a common mechanism. The expression of the targeted gene was examined by qPCR and Western blotting.Results: Ozone intraperitoneal injection reversed spatial learning and memory deficits associated with REM sleep deprivation, ameliorating pathological brain damage and down-regulating the hippocampal expression of Sema3A in rats after REM sleep deprivation. Conclusion: Ozone intraperitoneal injection alleviated sleep deprivation-induced spatial learning and memory deficits by protecting hippocampal neurons via down-regulation of the expression of Sema3A in the hippocampus.

Endogenous depression represents a severe mental health condition projected to become one of the worldwide leading causes of years lived with disability. The currently available clinical and non-clinical interventions designed to alleviate endogenous depression-associated symptoms encounter a series of inconveniences, from the lack of intervention effectiveness and medication adherence to unpleasant side effects. In addition, depressive individuals tend to be more frequent users of primary care units, which markedly affects the overall treatment costs. In parallel with the growing incidence of endogenous depression, researchers in sleep science have discovered multiple links between rapid eye movement (REM) sleep patterns and endogenous depression. Recent findings suggest that prolonged periods of REM sleep are associated with different psychiatric disorders, including endogenous depression. In addition, a growing body of experimental work confidently describes REM sleep deprivation (REM-D) as the underlying mechanism of most pharmaceutical antidepressants, proving its utility as either an independent or adjuvant approach to alleviating the symptoms of endogenous depression. In this regard, REM-D is currently being explored for its potential value as a sleep intervention-based method for improving the clinical management of endogenous depression. Therefore, this narrative review represents a comprehensive inventory of the currently available evidence supporting the potential use of REM-D as a reliable, non-pharmaceutical approach for treating endogenous depression, or as an adjuvant practice that could improve the effectiveness of currently used medication. [ABSTRACT FROM AUTHOR]

[Display omitted] • Methamphetamine and REM sleep deprivation exerted synergistic effects to increase hyperlocomotion and risk-taking behavior. • REM sleep deprivation alone induced an increased anxiety-like behavior in adolescent, but not in adult, rats. • Methamphetamine and REM sleep deprivation paradigms revealed synergistic effects to impair spatial working memory. • Neither methamphetamine nor REM sleep deprivation alone affected spatial working memory. Drug addiction may result in sleep problems. Importantly, sleep deprivation (SD) is known as an important risk factor for relapse to drug abuse as SD mimics the effects of psychostimulants on dopamine system of the brain. Moreover, aging may affect sleep and drug addiction. This study, therefore, set out to assess the effects of methamphetamine (METH) and REM sleep deprivation (RSD) on locomotor activity, anxiety-like behavior and spatial memory in adult and adolescent rats. Adult and adolescent male Wistar rats received a neurotoxic METH regimen; four subcutaneous injections of 6 mg/kg, at 2 h intervals. Five days later, the animals underwent a 48-h RSD episode using the multiple platforms method. They were then examined using the open field (OF), elevated plus maze (EPM) and Y-maze tasks. We found that the METH and RSD paradigms showed synergistic effects to increase locomotion and risk-taking behavior in both adult and adolescent animals, while only adolescent rats revealed RSD-induced anxiety-like behavior. Moreover, adolescent animals revealed greater sensitization for vertical activity following METH plus RSD episode. In addition, METH and RSD paradigms revealed synergistic effects to impair spatial working memory, but neither METH nor RSD alone affected performance of animals in the Y-maze task. Our findings may indicate that there are important relationships between METH and RSD to induce hyperlocomotion, risk-taking behavior and spatial memory impairment, particularly in adolescent animals. Moreover, it seems that adolescent rats may be more susceptible to anxiety-like behavior and hyperlocomotion than adults. [ABSTRACT FROM AUTHOR]

Caffeine is a psychostimulant substance that is mostly used to prevent fatigue, increase alertness, and ameliorate sleep loss situations. In this study, we aimed to investigate the effect of chronic caffeine consumption on learning and memory functions and related genes in rapid eye movement (REM) sleep-deprived rats. During the neonatal period (postnatal day [PND] 28) Wistar albino male rats (n = 32) were randomly assigned into four groups: Control (C), caffeine application (Cf), acute REM sleep-deprivation (RD), and caffeine application + acute RD (Cf + RD). The 48 h of RD was executed when caffeine administration was completed. The learning and memory performance was evaluated by the Morris water maze test (MWMT). Following this, the rats were decapitated to isolate hippocampus tissues. In MWMT, time spent in the targeted quadrant decreased significantly in the RD group compared with the C and Cf + RD group. NR2A expression level increased in the RD group compared with C, Cf, and Cf + RD groups (p < 0.05). NR2B expression level increased in RD and Cf + RD groups compared with C and Cf groups (p < 0.05). BDNF and c-Fos expression levels did not differ significantly between the groups. RD impaired hippocampal spatial memory performance in the MWMT test. Our results indicated that chronic caffeine consumption has a therapeutic effect on spatial memory deterioration impairment caused by RD. Furthermore, it seems that the effect of caffeine RD on the hippocampus may be mediated by NR2A. [ABSTRACT FROM AUTHOR]

The proinflammatory state, which may be induced by sleep deprivation, seems to be a determining factor in the development of neurodegenerative processes. Investigations of mechanisms that help to mitigate the inflammatory effects of sleep disorders are important. A new proposal involves the neurotransmitter dopamine, which may modulate the progression of the immune response by activating receptors expressed on immune cells. This study aimed to determine whether dopamine D2 receptor (D2DR) activation attenuates the proinflammatory response derived from rapid eye movement (REM) sleep deprivation in mice. REM sleep deprivation (RSD) was induced in 2-month-old male CD1 mice using the multiple platform model for three consecutive days; during this period, the D2DR receptor agonist quinpirole (QUIN) was administered (2 mg/kg/day i.p.). Proinflammatory cytokine levels were assessed in serum and homogenates of the brain cortex, hippocampus, and striatum using ELISAs. Long-term memory deficits were identified using the Morris water maze (MWM) and novel object recognition (NOR) tests. Animals were trained until learning criteria were achieved; then, they were subjected to RSD and treated with QUIN for 3 days. Memory evocation was determined afterward. Moreover, we found RSD induced anhedonia, as measured by the sucrose consumption test, which is commonly related to the dopaminergic system. Our data revealed increased levels of proinflammatory cytokines (TNFa and IL-1b) in both the hippocampus and serum from RSD mice. However, QUIN attenuated the increased levels of these cytokines. Furthermore, RSD caused a long-term memory evocation deficit in both the MWM and NOR tests. In contrast, QUIN coadministration during the RSD period significantly improved the performance of the animals. On the other hand, QUIN prevented the anhedonic condition induced by RSD. Based on our results, D2DR receptor activation protects against memory impairment induced by disturbed REM sleep by inhibiting neuroinflammation. [ABSTRACT FROM AUTHOR]

GABA B receptors play a modulatory role in the mechanisms underlying drug addiction, sleep problems, and aging; however, there are few studies addressing their relationship. Therefore, this study aimed to examine whether blockade of these receptors affects methamphetamine (METH) reward memory in adult and adolescent rapid-eye movement sleep deprived (RSD) rats. Adolescent and adult male Wistar rats were subjected to RSD for seven days. They were then conditioned to receive methamphetamine (METH; 2 mg/kg, ip) during an eight-day conditioning period. METH reward memory was then reactivated during a retrieval trial and the GABA B receptor agonist baclofen (2.5 or 5 mg/kg, ip) was injected prior to the retrieval trial. Afterward, animals were retested for the expression of conditioned place preference (CPP) and hippocampal expression of GABA B receptors. Baclofen dose-dependently decreased the retrieval of METH reward memory in control and RSD adult and adolescent rats, but its effects were stronger at the higher dose. Moreover, we found stronger effects of baclofen in adolescent animals than in adult ones. In addition, baclofen at its higher dose decreased GABA B overexpression in the hippocampus of adolescent rats, but not in adult rats. These findings shed new light on the mechanisms underlying the role of GABA B receptors in the retrieval of METH reward memory and highlight the importance of considering age and sleep patterns in understanding addiction. Further research could potentially lead to the development of therapeutics for individuals struggling with METH addiction., Competing Interests: Declaration of competing interest The authors have no conflicts to declare., (Copyright © 2024. Published by Elsevier Inc.)

Several signaling pathways that converge in NF-kB activation have been linked to developing and maintaining different types of pathological pain. In addition, some mechanisms implied in the establishment of chronic pain have been demonstrated to have a sex-dependent correlation. This study aimed to determine if the IKKs/NF-kB signaling pathway is involved in establishing REM sleep deprivation (REMSD) induced mechanical allodynia in rats and its possible regulation depending on estradiol and estrogen receptors. Intrathecal administration of BMS-345541 or minocycline, two drugs that reduce the IKKs/NF-kB activity, avoided the development of mechanical allodynia in female but not in male rats subjected to 48 h of REMSD. Ovariectomy in female rats abolished the effect of BMS-345541 and minocycline. Meanwhile, the 17-β-estradiol restitution restored it. Intrathecal administration of MPP, a selective ERα antagonist, but not PHTPP, a selective ERβ antagonist, avoided the effect of BMS-345541 in female rats without hormonal manipulation. In addition, the transient run-down of ERα in female rats abolished the effect of BMS-345541. All data suggest an important role of ERα as a regulator of the IKKs/NF-kB activity. REMSD increased the ERα protein expression in the dorsal root ganglia and the dorsal spinal cord in females but not in male rats. Interestingly, ERα activation or ERα overexpression allowed the effect of BMS-345541 in male rats. Data suggest an important regulatory role of ERα in the IKKs/NF-kB activity on establishing mechanical allodynia induced by REMSD in female rats., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The proinflammatory state, which may be induced by sleep deprivation, seems to be a determining factor in the development of neurodegenerative processes. Investigations of mechanisms that help to mitigate the inflammatory effects of sleep disorders are important. A new proposal involves the neurotransmitter dopamine, which may modulate the progression of the immune response by activating receptors expressed on immune cells. This study aimed to determine whether dopamine D2 receptor (D2DR) activation attenuates the proinflammatory response derived from rapid eye movement (REM) sleep deprivation in mice. REM sleep deprivation (RSD) was induced in 2-month-old male CD1 mice using the multiple platform model for three consecutive days; during this period, the D2DR receptor agonist quinpirole (QUIN) was administered (2 mg/kg/day i.p.). Proinflammatory cytokine levels were assessed in serum and homogenates of the brain cortex, hippocampus, and striatum using ELISAs. Long-term memory deficits were identified using the Morris water maze (MWM) and novel object recognition (NOR) tests. Animals were trained until learning criteria were achieved; then, they were subjected to RSD and treated with QUIN for 3 days. Memory evocation was determined afterward. Moreover, we found RSD induced anhedonia, as measured by the sucrose consumption test, which is commonly related to the dopaminergic system. Our data revealed increased levels of proinflammatory cytokines (TNFα and IL-1β) in both the hippocampus and serum from RSD mice. However, QUIN attenuated the increased levels of these cytokines. Furthermore, RSD caused a long-term memory evocation deficit in both the MWM and NOR tests. In contrast, QUIN coadministration during the RSD period significantly improved the performance of the animals. On the other hand, QUIN prevented the anhedonic condition induced by RSD. Based on our results, D2DR receptor activation protects against memory impairment induced by disturbed REM sleep by inhibiting neuroinflammation.

Objectives: Sleep 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 Methods: Twenty-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. Results: The serum NSE, CK-BB, and LDH-BB were significantly higher in 72 hour sleep deprived group compared to control (p0.05). Discussion: REM 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.

[Display omitted] • REMSD enhanced c-Fos and α2δ-1 protein expression in DRG and DSC. • CaCC inh-A01 and T16A inh-A01 reverted REMSD-induced tactile allodynia in rats. • T16A inh-A01 had a higher antiallodynic effect in male than female rats. • REMSD increased bestrophin-1 protein expression in DRG in male and female rats. • REMSD decreased anoctamin-1 protein expression in DSC cord in female 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 CaCC inh-A01 , a non-selective bestrophin-1 blocker, and T16A inh-A01 , a specific anoctamin-1 blocker, reverted REMSD-induced tactile allodynia. However, T16A inh-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. [ABSTRACT FROM AUTHOR]

Background: Insufficient sleep alters the body's physiological functions. This study investigated whether oxidative stress (OS) in the thalamus was correlated with the pain behaviour score in the rapid eye movement (REM) sleep-deprived rat model. Methods: Four groups of Sprague-Dawley rats were included in the study (n = 6): i) control; ii) REM sleep-deprived rats for 72 h (REMsd); iii) REM sleep-deprived rats for 72 h pretreated with Tualang honey (REMsd-H) and iv) tank control (TC). Following the intervention, 1% formalin was injected on the right hind paw and pain behaviour was recorded for 1 h. OS markers of glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in the thalamus were measured. Results: REM sleep deprivation increased pain behaviour scores in phase II of the formalin test with decreased GSH, GR, SOD and CAT. The MDA level was significantly higher in the REMsd compared to REMsd-H. There was an inverse correlation between pain behaviour scores and GSH, GR and SOD levels. A positive correlation was found between the pain behaviour score and the MDA level. Conclusion: OS levels were significantly correlated with the pain behaviour score in the REMsd rats. Tualang honey administration reduced pain behaviour score and OS in the thalamus. [ABSTRACT FROM AUTHOR]

Sleep deprivation has been shown to alter pain responses in humans and animals. The present study investigated whether the administration of Tualang honey in the rapid eye movement (REM) sleep deprivation rat model would modulate nociceptive responses with associated changes in the thalamus. Forty-eight Sprague Dawley male rats were randomised into four groups (n=12 for each group): control group (FMC), REM sleep deprivation (REMsd), REM sleep deprivation pretreated with Tualang Honey for 1 month (REMsdH) and tank control (TC). Following sleep deprivation for 72 hours, a formalin test was conducted and pain behaviour was recorded and analysed. The rats were sacrificed, and the brains were removed for histological examination and assessment of N-methyl-D-aspartate receptor (NMDA R2) level in the thalamus. REMsdH group showed a significantly lower level of pain behaviour score and NMDA R2 compared to the REMsd group (p<0.05). In addition, REMsdH also demonstrated a significantly higher number of Nissl stained neurons in comparison with the REMsd group (p<0.05). Furthermore, dark neurons, suggestive of neuronal damage, were observed in the REMsd group. In conclusion, administration of Tualang honey before REM sleep deprivation modulated nociceptive responses and prevent changes in thalamic neurons and NMDA R2 level. [ABSTRACT FROM AUTHOR]

Objective: Rapid eye movement sleep deprivation (REM-SD) can cause a decline in learning and memory and lead to changes in behavior. Therefore, REM sleep plays a key role in processes that govern learning and memory. However, the mechanism underlying REM-SD-induced learning and memory impairment is unclear and the underlying molecular signaling still needs to be identified. In the present study, we investigated the role of the cPKCγ-Ng signaling pathway in REM-SD-induced learning and memory impairment. Method: Sixty male rats were divided into Control, REM-SD, REM-SD+cPKCγ activator PMA, REM-SD+cPKCγ inhibitor H-7, and sleep revival (SR) groups. The Morris water maze was used to assess spatial learning and memory. Western blot analysis was used to detect cPKCγ total protein expression and membrane translocation levels, and Ng total protein expression and phosphorylation levels. Results: The REM-SD group performed worse on the Morris water maze test than the control group. Western blot analysis showed that cPKCγ membrane translocation and Ng phosphorylation levels were significantly lower in the REM-SD group. SR following REM-SD restored learning and memory ability, cPKCγ transmembrane translocation, and Ng phosphorylation levels, but not to levels observed before REM-SD. PMA and H-7 significantly improved/disrupted task ability as well as cPKCγ transmembrane translocation and Ng phosphorylation levels in REM-SD rats. Conclusion: The REM-SD induced learning and memory impairment in rats and may be associated with the cPKCγ-Ng signaling pathway. Specifically, activation of the cPKCγ-Ng signaling pathway may protect against REM-SD. [ABSTRACT FROM AUTHOR]

• Exenatide (GLP-1 receptor agonist) prevents from memory impairment induced by REM sleep deprivation for 24 h. • REM sleep deprivation decreases CaMKII and PSD95 levels in hippocampus and Exenatide normalizes CaMKII ratio in the hippocampus. • REM sleep deprivation induces depression-like behavior in FST and Exenatide treatment has no effect on this behavior. • Oxidant/antioxidant status is not changed by neither 72 h REM sleep deprivation nor treatment with exenatide. • REM sleep deprivation and treatment of exenatide did not affect anxiety-like behavior in EPM test. Previous investigations have shown that REM sleep deprivation impairs the hippocampus‐dependent memory, long-term potentiation and causing mood changes. The aim of the present study was to explore the effects of exenatide on memory performance, anxiety- and depression like behavior, oxidative stress markers, and synaptic protein levels in REM sleep deprived rats. A total of 40 male Wistar rats were randomly divided to control, exenatide-treated control, sleep deprivation (SD), wide platform (WP) and exenatide-treated SD groups. During experiments, exenatide treatment (0.5 μg/kg, subcutaneously) was applied daily in a single dose for 9 days. Modified multiple platform method was employed to generate REM sleep deprivation for 72 h. The Morris water maze test was used to assess memory performance. Anxiety- and depression-like behaviors were evaluated by open field test (OFT), elevated plus maze (EPM) forced swimming test (FST), respectively 72 h after REMSD. The levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and postsynaptic density proteins 95 (PSD95) were measured in tissues of hippocampus and prefrontal cortex. The content of malondialdehyde (MDA) and reduced glutathione (GSH) were also measured. In the present study, an impairment in memory was observed in SD rats at the 24th hour of SD in compare to those of other groups. REMSD increased depression-like behavior in FST as well as the number of rearing and crossing square in OFT. Anxiety is the most common comorbid condition with depressive disorders. Contents of CaMKII and PSD95 decreased in hippocampus of SD rats. Exenatide treatment improved the impaired memory of SD rats and increased CaMKII content in hippocampus There was no difference in MDA and GSH levels among groups. Exenatide treatment also diminished locomotor activity in OFT. In conclusion, treatment with exenatide, at least in part, prevented from these cognitive and behavioral changes possibly through normalizing CaMKII levels in the hippocampus. [ABSTRACT FROM AUTHOR]

Objective: Rapid eye movement sleep deprivation (REM-SD) can cause a decline in learning and memory and lead to changes in behavior. Therefore, REM sleep plays a key role in processes that govern learning and memory. However, the mechanism underlying REM-SD-induced learning and memory impairment is unclear and the underlying molecular signaling still needs to be identified. In the present study, we investigated the role of the cPKCγ-Ng signaling pathway in REM-SD-induced learning and memory impairment.Method: Sixty male rats were divided into Control, REM-SD, REM-SD+cPKCγ activator PMA, REM-SD+cPKCγ inhibitor H-7, and sleep revival (SR) groups. The Morris water maze was used to assess spatial learning and memory. Western blot analysis was used to detect cPKCγ total protein expression and membrane translocation levels, and Ng total protein expression and phosphorylation levels.Results: The REM-SD group performed worse on the Morris water maze test than the control group. Western blot analysis showed that cPKCγ membrane translocation and Ng phosphorylation levels were significantly lower in the REM-SD group. SR following REM-SD restored learning and memory ability, cPKCγ transmembrane translocation, and Ng phosphorylation levels, but not to levels observed before REM-SD. PMA and H-7 significantly improved/disrupted task ability as well as cPKCγ transmembrane translocation and Ng phosphorylation levels in REM-SD rats.Conclusion: The REM-SD induced learning and memory impairment in rats and may be associated with the cPKCγ-Ng signaling pathway. Specifically, activation of the cPKCγ-Ng signaling pathway may protect against REM-SD.

Excitotoxicity has been related to play a crucial role in Parkinson’s disease (PD) pathogenesis. Pedunculopontine tegmental nucleus (PPT) represents one of the major sources of glutamatergic afferences to nigrostriatal pathway and putative reciprocal connectivity between these structures may exert a potential influence on rapid eye movement (REM) sleep control. Also, PPT could be overactive in PD, it seems that dopaminergic neurons are under abnormally high levels of glutamate and consequently might be more vulnerable to neurodegeneration. We decided to investigate the neuroprotective effect of riluzole administration, a N-methyl-D-aspartate (NMDA) receptor antagonist, in rats submitted simultaneously to nigrostrial rotenone and 24h of REM sleep deprivation (REMSD). Our findings showed that blocking NMDA glutamatergic receptors in the SNpc, after REMSD challenge, protected the dopaminergic neurons from rotenone lesion. Concerning rotenone-induced hypolocomotion, riluzole reversed this impairment in the control groups. Also, REMSD prevented the occurrence of rotenone-induced motor impairment as a result of dopaminergic supersensitivity. In addition, higher Fluoro Jade C (FJC) staining within the SNpc was associated with decreased cognitive performance observed in rotenone groups. Such effect was counteracted by riluzole suggesting the occurrence of an antiapoptotic effect. Moreover, riluzole did not rescue cognitive impairment impinged by rotenone, REMSD or their combination. These data indicated that reductions of excitotoxicity, by riluzole, partially protected dopamine neurons from neuronal death and appeared to be effective in relieve specific rotenone-induce motor disabilities.

Abstract Background Disrupted sleep is associated with a reciprocal influence on headaches and is one of the contributing factors in the process of chronicity. The goal of the present study was to investigate the influence of sleep on headaches using animal rapid eye movement (REM) sleep deprivation and supradural capsaicin infusion models. Method Sprague-Dawley rats underwent REM sleep deprivation (REMSD) for 96 h. The sensory threshold to mechanical stimuli, assessed by the von Frey monofilament test, was measured during the REMSD period. Additionally, the Fos protein expression level was measured in the trigeminocervical complex, periaqueductal gray, and hypothalamus. Following supradural infusion of capsaicin, we evaluated the duration of facial allodynia for 28 days after REMSD. Results After REMSD, the sensory threshold to mechanical stimuli was significantly decreased (p

Harmane, as a neuromodulator, implicates in the learning and memory processes. However, rapid eye movement (REM) sleep deprivation negatively affects these processes. Here, we investigated the effects of harmane (2.5 mg/kg) on the regulation of fear memory in free moving groups (FMG), large platform groups (LPG) and REM-deprived mice. We employed a flower pot technique for REM sleep deprivation and a Pavlovian fear conditioning paradigm for assessment of fear memories. FMGs received two or three pre-training intraperitoneal administrations of harmane at 12 h intervals, impaired contextual memory retention but those received three harmane administrations showed an auditory memory disruption. LPGs, with or without harmane, did not alter fear memories compared to their respective FMGs, indicating the inability of stress on fear responses of FMGs. Moreover, 12, 24 and 36 h REM sleep deprivation impaired contextual memory retrieval, while 24 and 36 h REM sleep deprivation impaired auditory fear memory retention. Furthermore, harmane only abolished contextual and auditory fear memory deficits induced by 24 h REM sleep deprivation. The data suggests a modulatory role for harmane in REM sleep deprivation response on fear memory.

• Chronic REM sleep deprivation exposure induces anxiety-like behavior and cognitive impairment. • Chronic REM sleep deprivation exposure increases NE and DA, decreases 5-HT and GABA in mouse hippocampus. • Chronic REM sleep deprivation exposure reduces IGF-1 and BDNF levels in mouse hippocampus. • Exercise training ameliorates behavioral, neurochemical and neurobiological changes induced by chronic REM sleep deprivation. Various sleep disorders have deleterious effects on mental and cognitive performance. Exercise, as an alternative therapeutic strategy, exerts beneficial impacts on human health. In the present study, we aimed to evaluate the effects of 4 weeks treadmill exercise (4W-TE) on anxiety-like behavior and cognitive performance in mice exposed to 2 months REM sleep deprivation (2M-SD) (20 h per day). Behavioral performance of mice in elevated plus maze test (EPM), open field test (OFT), Y maze test (YM) and Morris water maze test (MWM) was recorded and analyzed 28 h after the last day of sleep deprivation. After behavioral tests, various neurotransmitters including norepinephrine (NE), dopamine (DA), serotonin (5-HT) and γ-aminobutyric acid (GABA) in mouse hippocampus were quantified using high performance liquid chromatography. The hippocampal levels of insulin-like growth factor-1 (IGF-1) and brain derived neurotrophic factor (BDNF) were further detected using ELISA. Behavioral data indicated that 2M-SD exposure induced anxiety-like behaviors and cognitive impairment, as evidenced by the decreased open-arm entries in EPM, reduced central area travels in OFT, declined spontaneous alteration in YM and prolonged escaping latency in MWM. In addition, 2M-SD exposure increased NE and DA, decreased 5-HT and GABA, and reduced IGF-1 and BDNF levels in mouse hippocampus. Interestingly, all these behavioral, neurochemical and neurobiological changes can be ameliorated by 4W-TE training. In summary, these findings confirm the beneficial impacts of exercise on health and provide further experimental evidence for future application of exercise as an alternative therapy against the mental and cognitive problems in patients with sleep disorders. [ABSTRACT FROM AUTHOR]

New Findings: 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 72 h (REMsd), tank control rats and 72 h sleep‐recovered rats after 72 h 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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: Rats were sleep deprived by the flower pot method and were then analyzed for various behaviors and biochemical tests. Lithium was supplemented in diet. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Abstract Sleep is essential for memory consolidation that stabilizes a memory trace. Memory consolidation includes waves of new gene expression and protein synthesis. Recently, microRNAs (miRNAs) have emerged as critical regulators of memory processes. Previous studies demonstrated that rapid eye movement (REM) sleep deprivation (REM SD) during specific time windows after training in the Morris water maze (MWM) task impairs memory consolidation. Here, we showed that the post-learning REM sleep, extending from 3 to 6 h after last training, is critical for spatial learning in the MWM task. Further, we found that the REM SD after training significantly changes the hippocampal expression of brain-derived neurotrophic factor (BDNF) mRNA; however, it causes minimal difference in the hippocampal expressions of calcium-calmodulin-dependent protein kinase II (CAMKII) and cAMP response-element-binding (CREB). In addition, it considerably affected the hippocampal expressions of miR-132, miR-182, and miR-124. In conclusion, after the MWM task, the post-learning REM sleep during specific time windows can modulate spatial memory consolidation, and its deprivation can impact the hippocampal transcriptional processes including memory-related miRNAs and mRNAs. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Repeated administration of a subthreshold dose of harmane impaired fear memories. • Stress did not alter harmane response on fear memory retention. • REM sleep deprivation, prior to training, impaired fear memories. • Harmane abolished fear memory deficits in REM sleep deprived mice during 24 h. • Harmane modulates conditioned fear memory in REM sleep deprived-mice. Abstract Harmane, as a neuromodulator, implicates in the learning and memory processes. However, rapid eye movement (REM) sleep deprivation negatively affects these processes. Here, we investigated the effects of harmane (2.5 mg/kg) on the regulation of fear memory in free moving groups (FMG), large platform groups (LPG) and REM-deprived mice. We employed a flower pot technique for REM sleep deprivation and a Pavlovian fear conditioning paradigm for assessment of fear memories. FMGs received two or three pre-training intraperitoneal administrations of harmane at 12 h intervals, impaired contextual memory retention but those received three harmane administrations showed an auditory memory disruption. LPGs, with or without harmane, did not alter fear memories compared to their respective FMGs, indicating the inability of stress on fear responses of FMGs. Moreover, 12, 24 and 36 h REM sleep deprivation impaired contextual memory retrieval, while 24 and 36 h REM sleep deprivation impaired auditory fear memory retention. Furthermore, harmane only abolished contextual and auditory fear memory deficits induced by 24 h REM sleep deprivation. The data suggests a modulatory role for harmane in REM sleep deprivation response on fear memory. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is a widely abused and a severely addictive psychostimulant. Relapse is the main cause of concern when treating addiction. It could manifest after a long period of abstinence. Previous studies showed that there is a strong connection between sleep impairment and relapse. Also, it has been reported that cannabidiol might be a potential treatment for drug craving and relapse. In this study, we used conditioned place preference (CPP) to investigate whether Cannabidiol (CBD), a phytocannabinoid, can prevent METH-induced reinstatement in Rapid Eye Movement Sleep Deprived (RSD) rats. In order to induce CPP, the animals were given METH (1 mg/kg; sc) for five days. The effective priming dose of METH (0.5 mg/kg, sc) reinstated the extinguished METH-induced CPP. In order to investigate the effect of RSD on METH-induced reinstatement, we used the inverted flowerpot technique to deprive the rats of REM sleep. We found that 24 h-RSD could facilitate priming-induced reinstatement of METH. In addition to this, the ICV administration of CBD 10 μg/5 μl could suppress the METH-induced reinstatement even in RSD rats. In conclusion, the administration of CBD 10 μg/5 μl effectively prevents METH-induced CPP, even in a condition of stress. CBD can be considered an agent that reduces the risk of the relapse; however, this requires more investigation. [ABSTRACT FROM AUTHOR]

Several efforts have been made to understand the involvement of rapid eye movement (REM) sleep for cognitive processes. Consolidation or retention of recognition memories is severely disrupted by REM sleep deprivation (REMSD). In this regard, pedunculopontine tegmental nucleus (PPT) and other brainstem nuclei, such as pontine nucleus (Pn) and oculomotor nucleus (OCM), appear to be candidates to take part in this REM sleep circuitry with potential involvement in cognition. Therefore, the objective of this study was to investigate a possible association between the performance of Wistar rats in a declarative memory and PPT, Pn, and OCM activities after different periods of REMSD. We examined c-Fos and choline acetyltransferase (ChaT) expressions as indicators of neuronal activity as well as a familiarity-based memory test. The animals were distributed in groups: control, REMSD, and sleep rebound (REB). At the end of the different REMSD (24, 48, 72, and 96 h) and REB (24 h) time points, the rats were immediately tested in the object recognition test and then the brains were collected. Results indicated that OCM neurons presented an increased activity, due to ChaT-labeling associated with REMSD that negatively correlated ( r = −0.32) with the cognitive performance. This suggests the existence of a cholinergic compensatory mechanism within the OCM during REMSD. We also showed that 24 h of REMSD impacted similarly in memory, compared to longer periods of REMSD. These data extend the notion that REM sleep is influenced by areas other than PPT, i.e., Pn and OCM, which could be key players in both sleep processes and cognition. [ABSTRACT FROM AUTHOR]

Introduction REM sleep deprivation is associated with impairment in learning and memory, and nicotine treatment has been shown to attenuate this effect. Recent studies have demonstrated the importance of DREAM protein in learning and memory processes. This study investigates the association of DREAM protein in REM sleep-deprived rats hippocampus upon nicotine treatment. Methods Male Sprague Dawley rats were subjected to normal condition, REM sleep deprivation and control wide platform condition for 72 hr. During this procedure, saline or nicotine (1 mg/kg) was given subcutaneously twice a day. Then, Morris water maze ( MWM) test was used to assess learning and memory performance of the rats. The rats were sacrificed and the brain was harvested for immunohistochemistry and Western blot analysis. Results MWM test found that REM sleep deprivation significantly impaired learning and memory performance without defect in locomotor function associated with a significant increase in hippocampus DREAM protein expression in CA1, CA2, CA3, and DG regions and the mean relative level of DREAM protein compared to other experimental groups. Treatment with acute nicotine significantly prevented these effects and decreased expression of DREAM protein in all the hippocampus regions but only slightly reduce the mean relative level of DREAM protein. Conclusion This study suggests that changes in DREAM protein expression in CA1, CA2, CA3, and DG regions of rat's hippocampus and mean relative level of DREAM protein may involve in the mechanism of nicotine treatment-prevented REM sleep deprivation-induced learning and memory impairment in rats. [ABSTRACT FROM AUTHOR]

Sleep disorders are associated with cognitive impairment. Selective rapid eye movement sleep (REMS) deprivation (REMSD) alters several physiological processes and behaviors. By employing NGS platform we carried out transcriptomic analysis in brain samples of control rats and those exposed to REMSD. The expression of genes involved in chromatin assembly, methylation, learning, memory, regulation of synaptic transmission, neuronal plasticity and neurohypophysial hormone synthesis were altered. Increased transcription of BMP4, DBH and ATP1B2 genes after REMSD supports our earlier findings and hypothesis. Alteration in the transcripts encoding histone subtypes and important players in chromatin remodeling was observed. The mRNAs which transcribe neurotransmitters such as OXT, AVP, PMCH and LNPEP and two small non-coding RNAs, namely RMRP and BC1 were down regulated. At least some of these changes are likely to regulate REMS and may participate in the consequences of REMS loss. Thus, the findings of this study have identified key epigenetic regulators and neuronal plasticity genes associated to REMS and its loss. This analysis provides a background and opens up avenues for unraveling their specific roles in the complex behavioral network particularly in relation to sustained REMS-loss associated changes. [ABSTRACT FROM AUTHOR]

REM sleep rebound is a common behavioural response to some stressors and represents an adaptive coping strategy. Animals submitted to multiple, intermittent, footshock stress (FS) sessions during 96 h of REM sleep deprivation (REMSD) display increased REM sleep rebound (when compared to the only REMSD ones, without FS), which is correlated to high plasma prolactin levels. To investigate whether brain prolactin plays a role in stress-induced REM sleep rebound two experiments were carried out. In experiment 1, rats were either not sleep-deprived (NSD) or submitted to 96 h of REMSD associated or not to FS and brains were evaluated for PRL immunoreactivity (PRL-ir) and determination of PRL concentrations in the lateral hypothalamus and dorsal raphe nucleus. In experiment 2, rats were implanted with cannulas in the dorsal raphe nucleus for prolactin infusion and were sleep-recorded. REMSD associated with FS increased PRL-ir and content in the lateral hypothalamus and all manipulations increased prolactin content in the dorsal raphe nucleus compared to the NSD group. Prolactin infusion in the dorsal raphe nucleus increased the time and length of REM sleep episodes 3 h after the infusion until the end of the light phase of the day cycle. Based on these results we concluded that brain prolactin is a major mediator of stress-induced REMS. The effect of PRL infusion in the dorsal raphe nucleus is discussed in light of the existence of a bidirectional relationship between this hormone and serotonin as regulators of stress-induced REM sleep rebound. [ABSTRACT FROM AUTHOR]

Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats. Accordingly, REM-SD caused a significant decrease of pCREB in hippocampus and striatum and a significant decrease of BDNF in the hippocampus, striatum and amygdala, however, MP-10 reversed the effects of REM-SD in a dose-dependent manner. Our findings suggest that REM-SD disrupts the consolidation of long-term fear memory and that administration of MP-10 protects the REM-SD-induced deficits in fear memory, which may be due to the MP-10-induced expression of BDNF in the hippocampus, striatum and amygdala, and phosphorylation of CREB in the hippocampus and striatum. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) affects spatial memory and proliferation in the dentate gyrus. It is unknown whether these deleterious effects persist in the long run. The aim of this study was to evaluate the proliferation, differentiation and maturation of neural progenitors as well as spatial memory 21 days after suffering sleep deprivation. Sixty-day old male Balb/C mice were exposed to 72-h REM-SD. Spatial memory, cell fate, apoptosis and expression levels of insulin-like growth factor 1 receptor (IGF-1R) were evaluated in the hippocampus at 0, 14 and 21 days after SD or control conditions. After 21-d recovery period, memory performance was assessed with the Barnes maze, we found a significant memory impairment in SD mice vs. control (94.0 ± 10.2s vs. 25.2 ± 4.5s; p < 0.001). The number of BrdU+ cells was significantly decreased in the SD groups at day 14 (controls = 1.6 ± 0.1 vs. SD mice = 1.2 ± 0.1 cells/field; p=0.001) and at day 21 (controls = 0.2 ± 0.03 vs. SD mice = 0.1 ± 0.02 cells/field; p < 0.001). A statistically significant decrease was observed in neuronal differentiation (1.4 ± 0.1 cells/field vs. 0.9 ± 0.1 cells/field, p = 0.003). Apoptosis was significantly increased at day 14 after SD (0.53 ± 0.06 TUNEL+ cells/field) compared to controls (0.19 ± 0.03 TUNEL+ cells/field p

AIM: Ginkgo-biloba extract contains ginkgo-flavone glycosides and has free-radical scavengers and platelet activating factor antagonist activity. Recent studies have also shown effects in modulation of pain. In this study, the antinociceptive effect of Ginkgo-Biloba was investigated in a model of REM sleep deprivation-induced hyperalgesia. METHODS: After ethical approval, 40 female Wistar-Albino rats, 8-12 weeks old, were divided into five groups of eight animals each (PLS, placebo; GB30, Ginkgo-Biloba 30mg/kg; GB100, Ginkgo-Biloba 100mg/kg; GB300, Ginkgo-Biloba 300mg/kg and FLP40, flurbiprofen 40mg/kg). Flurbiprofen was added as a positive control. All groups were included in the 72-hour REM sleepdeprivation protocol with the modified multiple-pot technique and pain assessment was performed with hot-plate and tail-flick tests at the beginning, end and after drug administration of the sleepdeprivation period. Mean values for pain assessment were produced from triple-measurements and expressed in seconds. Drugs and placebo were administered by single-dose gastricgavage after measurements after sleep-deprivation. In order to compare pre and post sleep-deprivation pain measurements between groups, the change from the first test to the post-test was calculated for each condition. Kolmogorov-Smirnov was used to determine the normal distribution of the groups, and one-way ANOVA and Post-hoc Tukey were used to determine the difference between groups in pain measurements. RESULTS: Sleep-deprivation caused hyperalgesia in all groups. (Hot-plate time decreased at the stated rates: PLS=60.8%, GB30=65.8%, GB100=65.9%, GB300=67.5%, FLP40=70.8% (p<0.05); Decreases in tail-flick test: PLS=67.2%, GB30=67.7%, GB100=58%, GB300=71.4%, FLP40=64.6% (p<0.05). Ginkgo-biloba showed analgesic effect at all doses (Hot-plate: GB30=30%, GB100=28%, Tail-flick: GB30=24%, GB100=26.9%) (p<0.05). Especially at a dose of 300mg/kg, its effect was closest to flurbiprofen in the tail-flick test. (Hot-plate: GB300=43.5%, FLP40=94.8%, tail-flick GB300=43.7%, FLP40=48.5%) (p<0.05). CONCLUSION: Ginkgo Biloba reduces the decrease in pain threshold due to sleep-deprivation and has an antinociceptive effect. We think that Ginkgo-Biloba has the potential to be added to the treatment in painful-symptoms associated with sleepdisorders. [ABSTRACT FROM AUTHOR]

AIM: REM sleep deprivation (SD) affects various physiological processes such as learning and memory. The effect of ethyl pyruvate on cognitive functions has been studied in a limited number of studies and has not been investigated on sleep deprivation before. Therefore, the aim of our study was to investigate the effects of ethyl pyruvate treatment on learning and memory in female rats undergoing REMSD for 72 hours. METHODS: 25 female Wistar albino rats aged 6months were divided into four different groups(7 sleep deprived rats, the others 6 rats). Control, wide platform(WP),SD,SD groups treated with ethyl pyruvate. WP group rats were placed in a tank with a large platform(13cm diameter) as environmental control of sleep deprivation. The rats in the WP group, which could sleep without falling into the water, remained in the tank for 72 hours. REMSD was created using the multi-platform(6.5cm diameter) method for 72 hours. Ethyl pyruvate treatment(50 mg/kg) was administered as a single daily dose(i.p) for 5 days. The Morris water maze(MWM) test was used to evaluate the effects of ethyl pyruvate on learning and memory. At the end of the experiment, the hippocampus and brain tissues of the rats were taken. RESULTS: The results showed that the effects of SD on memory assessed by the MWM test were prolonged in the daily time to find the platform and shortened in the time spent in the platform area on the last day (p<0.05). It also proved that SD increased MDA and nitrate levels in brain tissue and AchE activity in hippocampus tissue (p<0.05). When the ethyl pyruvate treatment group was compared with the SD group, nitrate levels were found to be decreased (p<0.05). Finally, it was found that there was no difference between the groups in terms of GSH and glycogen levels. CONCLUSION: Our results show that ethyl pyruvate administered after 72 hours of REMSD has no effect on learning and memory in young female rats. [ABSTRACT FROM AUTHOR]

AIM: Sleep deprivation (SD) affects levels of inflammatory mediators that cause various effects on metabolism. Uridine, the main pyrimidine nucleoside in humans, has been shown to have anti-apoptotic and anti-oxidant as well as neuroprotective effects. Our aim is to investigate effects of uridine on inflammatory mediators in REM sleep deprived rats. METHODS: Adult male Wistar albino rats (n=42) were randomized to 6 groups according to cages they were placed and uridine (1 mmol/kg)/Saline (1ml/kg) injections; CC+S: Saline treated control cage group, CC+U: Uridine treated control cage group, EC+S: Saline treated environmental control group, EC+U: Uridine treated control group, SD+S: Saline treated sleep deprivation group, and SD+U: Uridine treated sleep deprivation group. SD was induced by modified multiple platform method. A grid was placed on multiple platforms for environmental control cages. Rats were tracked for 96h and treated with U/S twice for 4 days and once on the 5thday intraperitoneally. Cytokine levels and mRNA expressions from hippocampi were analyzed by ELISA and RT-PCR methods. Groups were compared using ANOVA and post-hoc Tukey tests. RESULTS: IL-1β(p<0.001), IL-4(p<0.01), IL-6(p<0.01), IL-10(p<0.05) and TNF-α(p<0.001) levels increased in SD+S compared to CC+S. IL-1β(p<0.01), IL-4(p<0.001), IL-6(p<0.05) and TNF-α(p<0.05) levels increased in EC+S compared to CC+S. IL-1β(p<0.05) and IL-4(p<0.01) levels decreased in EC+U compared to EC+S. IL-1β(p<0.01), IL-4(p<0.001) and IL-6(p<0.001) mRNA expressions increased in SD+S compared to CC+S. IL-1β(p<0,01), IL-4(p<0,01), IL-17A (p<0,01) and TNF-α (p<0,05) mRNA expressions increased in EC+S compared to CC+S. mRNA expressions of IL-1β (p<0.001) decreased; IL-4 (p<0,01) and IL-6(p<0,001) increased in EC+U compared to EC+S. mRNA expressions of IL-1β(p<0.001) decreased; IL-6(p<0,001), IL-4(p<0,001) and TNF-α(p<0,05) increased in SD+U compared to SD+S. CONCLUSION: We determine that SD ameliorates cytokine levels and mRNA expressions in rats. The effects of uridine on cytokine levels and mRNA expressions in REM sleep deprived rats were shown for the first time in our study (TÜBİTAK Project No: 119S887). [ABSTRACT FROM AUTHOR]

AIM: Resveratrol is a naturally occurring polyphenol found in a variety of food products. Studies have demonstrated the existence of anti-inflammatory, neuroprotective and antinociceptive effects of Resveratrol. In this study, the antinociceptive effect of Resveratrol was investigated in a 72-hour REM sleep deprivationinduced hyperalgesia model. METHODS: After ethical approval, 40 male Wistar Albino rats, 8-12 weeks old, were divided into four groups of ten animals (PLS, placebo; RES2, Resveratrol 2mg/kg; RES5 Resveratrol 5mg/kg; RES10, Resveratrol 10mg/kg). All groups were subjected to 72-hour REM sleep deprivation protocol using modified multiple pot technique and pain assessment was performed with hot-plate and tail-flick tests at the beginning, end and after drug administration of the sleep-deprivation period. Mean values for pain assessment were produced from triple measurements and expressed in seconds. Following post-sleep-deprivation measurements, drugs and placebo were administered as a single dose by intraperitoneal injection. In order to compare the hot-plate and tail-flick measurements between groups before and after sleepdeprivation, the change from the first test to the post test was calculated for each condition. Kolmogorov-Smirnov was used to determine the normal distribution of the groups, and one-way ANOVA and Post-hoc Tukey were used to determine the difference between groups in pain measurements. RESULTS: Sleep deprivation caused hyperalgesia in all groups (Hotplate time decreased at the stated rates: PLS=51.1%; RES2=63.4%; RES5=60,4%; RES10=60.6% (p<0,05); decreases in tail-flick test PLS=53.2%, RES2=56.5%, RES5=70.9%, RES10=66.3% (p<0,05). Resveratrol showed an analgesic effect at a dose of 10mg/kg (Hotplate pain measurement change PLS = 13.8% decreased while RES10=37.5% increase (p<0,05); tail-flick PLS =19.6% decreased, RES10=21.9% increase) (p<0,05). CONCLUSION: Resveratrol showed analgesic effect in sleep deprivation-related pain model. This finding suggests that it has the potential to be used in the treatment of painful syndromes associated with sleep disturbance in the clinic. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) affects spatial memory and proliferation in the dentate gyrus. It is unknown whether these deleterious effects persist in the long run. The aim of this study was to evaluate the proliferation, differentiation and maturation of neural progenitors as well as spatial memory 21 days after suffering SD. Sixty-day old male Balb/C mice were exposed to 72-h REM-SD. Spatial memory, cell fate, apoptosis and expression levels of insulin-like growth factor 1 receptor (IGF-1R) were evaluated in the hippocampus at 0, 14, and 21 days after SD or control conditions. After 21-days recovery period, memory performance was assessed with the Barnes maze, we found a significant memory impairment in SD mice vs. control (94.0 ± 10.2 s vs. 25.2 ± 4.5 s; p < 0.001). The number of BrdUC cells was significantly decreased in the SD groups at day 14 (controls = 1.6 ± 0.1 vs. SD mice = 1.2 ± 0.1 cells/field; p = 0.001) and at day 21 (controls = 0.2 ± 0.03 vs. SD mice = 0.1 ± 0.02 cells/field; p < 0.001). A statistically significant decrease was observed in neuronal differentiation (1.4 ± 0.1 cells/field vs. 0.9 ± 0.1 cells/field, p = 0.003). Apoptosis was significantly increased at day 14 after SD (0.53 ± 0.06 TUNELC cells/field) compared to controls (0.19 ± 0.03 TUNELC cells/field p < 0.001) and at 21-days after SD (SD mice 0.53 ± 0.15 TUNELC cells/field; p = 0.035). At day 0, IGF-1R expression showed a statistically significant reduction in SD animals (64.6 ± 12.2 units) when compared to the control group (102.0 ± 9.8 units; p = 0.043). However, no statistically significant differences were found at days 14 and 21 after SD. In conclusion, a single exposition to SD for 72-h can induce deleterious effects that persist for at least 3 weeks. These changes are characterized by spatial memory impairment, reduction in the number of hippocampal BrdUC cells and persistent apoptosis rate. In contrast, changes IGF-1R expression appears to be a transient event. Highlight Sleep deprivation affects spatial memory and proliferation in the dentate gyrus. To date it is unknown whether these deleterious effects are persistent over a long period of time. We analyzed the effects of sleep deprivation in the hippocampus after 21 days of recovery sleep. Our findings indicate that after sleep recovery, the detrimental effects of SD can be observed for at least 2 weeks, as shown by a reduction in memory performance, changes in the hippocampal cellular composition and higher apoptotic rate over a long period of time. [ABSTRACT FROM AUTHOR]

Olfactory and rapid eye movement (REM) sleep deficits are commonly found in untreated subjects with a recent diagnosis of Parkinson's disease (PD). Besides different studies reported declines in olfactory performances during a short period of sleep deprivation. Mechanisms underlying these clinical manifestations are poorly understood although the impairment in the dopamine (DA) neurotransmission in the olfactory bulb and in the nigrostriatal pathway may have important roles in olfactory as well as in REM sleep disturbances. Therefore, we have led to the hypothesis that a modulation of the dopaminergic D2 receptors in the olfactory bulb could provide a more comprehensive understanding of the olfactory deficits in PD and after a short period of REM sleep deprivation (REMSD). We decided to investigate the olfactory, neurochemical and histological alterations generated by the administration of piribedil (a selective D2 agonist) or raclopride (a selective D2 antagonist), within the glomerular layer of the olfactory bulb, in rats submitted to intranigral rotenone and REMSD. Our findings provided a remarkable evidence of the occurrence of a negative correlation (r = - 0.52, P = 0.04) between the number of periglomerular TH-ir neurons and the bulbar levels of DA in the rotenone, but not sham groups. A significant positive correlation (r = 0.34, P = 0.03) was observed between nigral DA and olfactory discrimination index (DI), for the sham groups, indicating that increased DA levels in the substantia nigra pars compacta (SNpc) are associated to enhanced olfactory discrimination performance. Also, increased levels in bulbar and striatal DA induced by piribedil in the rotenone control and rotenone REMSD groups were consistent with reduced amounts of DI. The present evidence reinforce that DA produced by periglomerular neurons, and particularly the bulbar dopaminergic D2 receptors, are essential participants in the olfactory discrimination processes, as well as SNpc and striatu