Methamphetamine and REM sleep deprivation interact to affect behavioral performance in adult and adolescent rats.

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.

Noradrenaline enhances Na-K ATPase subunit expression by HuR-induced mRNA stabilization and their transportation to the cell surface through PLC and PKC mediated pathway: Implications with REMS-loss associated disorders.

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, ß-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 ß-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.

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.

Baseline prepulse inhibition dependency of orexin A and REM sleep deprivation.

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.

Chronic REM sleep deprivation leads to manic- and OCD-related behaviors, and decreases hippocampal BDNF expression in female rats.

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.

Photomodulatory effects in the hypothalamus of sleep-deprived young and aged rats.

Insufficient sleep is associated with impaired hypothalamic activity and declined attentional performance. In this study, alterations in the hypothalamus of REM sleep-deprived (SD) young and aged rats, and the modulatory effect of near-infrared (NIR) laser were investigated. Forty-eight male Wistar rats (24 young at 2 months and 24 senile at 14 months) were divided into three groups: the control, the SD group subjected to 72 hr of sleep deprivation, and the transcranial-NIR laser-treated (TLT) group subjected to SD for 72 hr and irradiated with 830 nm laser. The hypothalamic levels of oxidative stress, inflammatory biomarkers, antioxidant enzymes, mitochondrial cytochrome C oxidase (CCO), apoptotic markers (BAX, BCL-2), and neuronal survival-associated genes (BDNF, GLP-1) were evaluated. Furthermore, the hypothalamic tissue alterations were analyzed via histological examination. The results revealed that TLT treatment has enhanced the antioxidant status, prevented oxidative insults, suppressed neuroinflammation, regulated CCO activity, reduced apoptotic markers, and tuned the survival genes (BDNF & GLP-1) in hypothalamic tissue of SD young and aged rats. Microscopically, TLT treatment has ameliorated the SD-induced alterations and restored the normal histological features of hypothalamus tissue. Moreover, the obtained data showed that SD and NIR laser therapy are age-dependent. Altogether, our findings emphasize the age-dependent adverse effects of SD on the hypothalamus and suggest the use of low-laser NIR radiation as a potential non-invasive and therapeutic approach against SD-induced adverse effects in young and aged animals.

Role of Cannabinoid CB1 Receptor in Object Recognition Memory Impairment in Chronically Rapid Eye Movement Sleep-deprived Rats.

Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor (CB1R) could affect novel object recognition (NOR) memory in chronically rapid eye movement sleep-deprived (RSD) rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique. The CB1R 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.Results 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.Conclusions 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 CB1R 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.

A Narrative Review on REM Sleep Deprivation: A Promising Non-Pharmaceutical Alternative for Treating Endogenous Depression.

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.

Role of Cannabinoid CB1 Receptor in Object Recognition Memory Impairment in Chronically Rapid Eye Movement Sleep-deprived Rats / 中国医学科学杂志(英文版)

Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor (CB1R) could affect novel object recognition (NOR) memory in chronically rapid eye movement sleep-deprived (RSD) rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique. The CB1R 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.Results 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.Conclusions 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 CB1R 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.

Activation of dopamine D2 receptors attenuates neuroinflammation and ameliorates the memory impairment induced by rapid eye movement sleep deprivation in a murine model.

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-1ß) 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.

Intraperitoneal ozone injection prevents REM sleep deprivation - induced spatial learning and memory deficits by suppressing the expression of Sema3A in the hippocampus in rats.

Objectives: 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.

Synergistic antidepressant effects of citalopram and SB-334867 in the REM sleep-deprived mice: Possible role of BDNF.

This study was done to evaluate the effect of co-treatment of orexin agents along with citalopram on the modulation of depression-like behavior and the expression of BDNF in the prefrontal cortex (PFC) of sleep-deprived male mice. A sleep deprivation model was performed in which rapid eye movement (REM) sleep was completely prohibited, and non-REM sleep was intensely reduced for 24 h. For drug microinjection, the guide cannula was surgically fixed in the left lateral ventricle of mice. Furthermore, we used the open-field test (OFT), forced swim test (FST), tail suspension test (TST), and splash test for recording depression-like behavior as well as Real-Time PCR amplification for assessing the expression of BDNF in the PFC of REM sleep-deprived mice. Our results revealed that REM sleep deprivation did not change locomotor activity while increased depressive-like behavior in FST, TST, and splash tests. However, the expression of BDNF was decreased in the PFC. Intraperitoneally (i.p.) administration of citalopram induced antidepressant effect in the normal and REM sleep-deprived mice. Moreover, intracerebroventricular (i.c.v.) microinjection of a non-effective dose of SB-334867, an orexin antagonist, potentiated the antidepressant-like effect of citalopram. On the other hand, a non-significant dosage of orexin-1 reversed the antidepressant effect of citalopram in the normal and REM sleep-deprived animals. Furthermore, our results showed that injection of citalopram alone or with SB-334867 increased the mRNA expression level of BDNF in the PFC of REM sleep-deprived mice. These data suggest that REM sleep deprivation interferes with the neural systems underlying the depression-like process and supports a likely interaction of the orexin system with citalopram on the modulation of depression-like behavior in REM sleep-deprived mice.

Chronic caffeine consumption improves the acute sleep deprivation-induced spatial memory impairment while altering N-methyl-D-aspartate receptor subunit expression in male rats.

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.

Impact of Rapid Eye Movement Sleep Deprivation on Pain Behaviour and Oxidative Stress in the Thalamus: Role of Tualang Honey Supplementation.

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.

REM sleep deprivation before extinction or reinstatement alters methamphetamine reward memory via D1-like dopamine receptors.

We aimed to determine whether REM sleep deprivation (RSD) affects extinction and reinstatement of methamphetamine (METH) reward memory in male rats and also to evaluate the possible role of dopamine D1-like and D2-like dopamine (DA) receptors in these processes. Male rats were trained to acquire METH-induced place preference (2 mg/kg, i.p.). METH reward memory was then reinstated following a 10-day extinction period. The animals underwent a 72-hour sleep deprivation episode by multiple platforms method (in separate groups), either before the extraction or before the reinstatement of METH reward memory. The animals received SCH 23390 (0.01 or 0.05 mg/kg, i.p.) or sulpiride (20 or 60 mg/kg, i.p.) as antagonists of D1-like and D2-like DA receptors, respectively, either immediately following each daily extinction session or before the reinstatement of METH-seeking behavior. The RSD episode postponed extinction and facilitated reinstatement of METH reward memory. Administration of SCH 23390, but not sulpiride, facilitated METH extinction and decreased reinstatement of the extinguished METH-seeking behavior. Moreover, locomotor activity was not affected by METH and/or the RSD paradigm. The results would seem to suggest that the D1-like, but not the D2-like, DA receptors may be involved in the extinction and reinstatement of the extinguished METH reward memory in RSD animals. Nonetheless, more investigations are needed to elucidate the exact mechanisms involved.

Effect of the cPKCγ-Ng Signaling System on Rapid Eye Movement Sleep Deprivation-Induced Learning and Memory Impairment in Rats.

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.

The effects of glucagon-like peptide 1 receptor agonist (exenatide) on memory impairment, and anxiety- and depression-like behavior induced by REM sleep deprivation.

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.

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

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 (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). 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.

Corrigendum: Effect of the cPKCγ-Ng Signaling System on Rapid Eye Movement Sleep Deprivation-Induced Learning and Memory Impairment in Rats.

[This corrects the article DOI: 10.3389/fpsyt.2021.763032.].

Treadmill exercise ameliorates chronic REM sleep deprivation-induced anxiety-like behavior and cognitive impairment in C57BL/6J mice.

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.