Relationship between circadian rhythm-related genes and extracellular matrix: implications for sleep deprivation.

BACKGROUND: Sleep deprivation (SD) can lead to the development of various pathological disorders. The extracellular matrix (ECM) compositions and circadian rhythm genes are two pivotal variables of SD. However, their relationships remain undefined during SD. METHODS: A mouse SD model was established using a modified multiplatform water environment method. The expression of nerve growth factor (NGF) in mouse hippocampus was detected by an immunofluorescence (IF) method. Protein expression was assessed by western blot, and mRNA analysis was performed by quantitative real-time PCR (qRT-PCR). The differentially expressed genes after SD, the genes associated with stromal score, and gene expression correlation were analyzed by bioinformatic analysis. RESULTS: The mouse model of SD was successfully established, as evidenced by the changed morphology, increased Bax and NGF levels, and downregulated Bcl-2 in mouse hippocampus after SD. The differentially expressed genes after SD were closely associated with the ECM compositions. The ECM composition metalloproteinase 9 (MMP9) was under-expressed in mouse hippocampus after SD. The hippocampal MMP9 expression was correlated with the expression levels of circadian genes PER2, PER3, TIMELESS, FBXL3, and NFIL3. PER2 and TIMELESS were upregulated in mouse hippocampus after SD. CONCLUSION: The current findings suggest a correlation between ECM composition MMP9 and circadian rhythm-related genes PER2 and TIMELESS in mouse hippocampus after SD, providing a novel understanding of the disorders after SD.

PirB negatively regulates the inflammatory activation of astrocytes in a mouse model of sleep deprivation.

Reactive astrocytes play a potential regulatory role in sleep deprivation (SD). Paired immunoglobulin-like receptor B (PirB) is expressed in reactive astrocytes, suggesting that PirB may participate in regulating the inflammatory response of astrocytes. We used lentiviral and adeno-associated viral approaches to interfere with the expression of PirB in vivo and in vitro. C57BL/6 mice were sleep deprived for 7 days and neurological function was measured via behavioral tests. We found that overexpressed PirB in SD mice could decrease the number of neurotoxic reactive astrocytes, alleviate cognitive deficits, and promote reactive astrocytes tended to be neuroprotective state. IL-1α, TNFα, and C1q were used to induce neurotoxic reactive astrocytes in vitro. Overexpression of PirB relieved the toxicity of neurotoxic astrocytes. Silencing PirB expression had the opposite effect and exacerbated the transition of reactive astrocytes to a neurotoxic state in vitro. Moreover, PirB-impaired astrocytes demonstrated STAT3 hyperphosphorylation which could be reversed by stattic (p-STAT3 inhibitor). Furthermore, Golgi-Cox staining confirmed that dendrite morphology defects and synapse-related protein were significantly increased in PirB-overexpressed SD mice. Our data demonstrated that SD induced neurotoxic reactive astrocytes and contributed to neuroinflammation and cognitive deficits. PirB performs a negative regulatory role in neurotoxic reactive astrocytes via the STAT3 signaling pathway in SD.

The Interaction Effect of Sleep Deprivation and Treadmill Exercise in Various Durations on Spatial Memory with Respect to the Oxidative Status of Rats.

Sleep deprivation (SD) has deleterious effects on cognitive functions including learning and memory. However, some studies have shown that SD can improve cognitive functions. Interestingly, treadmill exercise has both impairment and improvement effects on memory function. In this study, we aimed to investigate the effect of SD for 4 (short-term) and 24 (long-term) hours, and two protocols of treadmill exercise (mild short-term and moderate long-term) on spatial memory performance, and oxidative and antioxidant markers in the serum of rats. Morris Water Maze apparatus was used to assess spatial memory performance. Also, SD was done using gentle handling method. In addition, the serum level of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) was measured. The results showed that 24 h SD (but not 4 h) had negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Long-term moderate (but not short-term mild) treadmill exercise had also negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Interestingly, both protocols of treadmill exercise reversed spatial memory impairment and oxidative stress induced by 24 h SD. In conclusion, it seems that SD and treadmill exercise interact with each other, and moderate long-term exercise can reverse the negative effects of long-term SD on memory and oxidative status; although, it disrupted memory function and increased oxidative stress by itself.

Dose-dependent manner of luteolin in the modulation of spatial memory with respect to the hippocampal level of HSP70 and HSP90 in sleep-deprived rats.

Sleep deprivation (SD) induces a variety of deleterious effects on different cognitive functions such as memory. Elevated neuroinflammation, oxidative stress, and apoptosis, and decreased synaptic plasticity and antioxidant capacity are involved in the deleterious effects of SD on memory. On the other hand, luteolin (a flavonoid compound) has antioxidant, neuroprotective, and anti-inflammatory properties. Also, Heat shock protein 70 (HSP70) and Heat shock protein 90 (HSP90) can be involved in modulating memory. In this study, we aimed to assess the effects of SD and luteolin on spatial learning and memory using Morris Water Maze apparatus in rats, with respect to the level of HSP70 and HSP90 in the hippocampus. Luteolin was injected intracerebroventricular (i.c.v.) at the doses of 0.5, 1, and 2 µg/rat. The results showed that SD impaired spatial memory, while luteolin dose-dependently restored SD-induced spatial memory impairment. SD increased the expression level of HSP90 in the hippocampus, whereas luteolin dose-dependently reversed the effect of SD. Furthermore, SD decreased the expression level of HSP70 protein in the hippocampus, while luteolin dose-dependently reversed the effect of SD. In conclusion, HSP70 and HSP90 may be involved in the deleterious effect of SD on memory, and in the improvement effect of luteolin on memory. This is a novel study reporting novel data and we suggest further detailed studies to better understand the interactions between SD, luteolin, and Heat shock proteins.

Intricate role of sleep deprivation in modulating depression: focusing on BDNF, VEGF, serotonin, cortisol, and TNF-α.

In this review article, we aimed to discuss intricate roles of SD in modulating depression in preclinical and clinical studies. Decades of research have shown the inconsistent effects of SD on depression, focusing on SD duration. However, inconsistent role of SD seems to be more complicated, and SD duration cannot be the only one factor. Regarding this issue, we chose some important factors involved in the effects of SD on cognitive functions and mood including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), serotonin, cortisol, and tumor necrosis factor-alpha (TNF-α). It was concluded that SD has a wide-range of inconsistent effects on BDNF, VEGF, serotonin, and cortisol levels. It was noted that BDNF diurnal rhythm is significantly involved in the modulatory role of SD in depression. Furthermore, the important role of VEGF in blood-brain barrier permeability which is involved in modulating depression was discussed. It was also noted that there is a negative correlation between cortisol and BDNF that modulates depression. Eventually, it was concluded that TNF-α regulates sleep/wake cycle and is involved in the vulnerability to cognitive and behavioral impairments following SD. TNF-α also increases the permeability of the blood-brain barrier which is accompanied by depressive behavior. In sum, it was suggested that future studies should focus on these mechanisms/factors to better investigate the reasons behind intricate roles of SD in modulating depression.

The role of sleep deprivation in streptozotocin-induced Alzheimer's disease-like sporadic dementia in rats with respect to the serum level of oxidative and inflammatory markers.

Numerous studies have shown the deleterious effects of sleep deprivation (SD) on memory. However, SD in various durations may induce different effects. Studies have reported that short-term or acute SD can improve cognitive functions. In addition, streptozotocin (STZ) significantly impairs learning and memory, and induces inflammation and oxidative stress. In this study, we aimed to investigate the effect of two types of SD (short term: 6 h; long term: 24 h) on STZ-induced spatial memory impairment in rats, with respect to the serum level of catalase (CAT), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1ß). Morris water maze apparatus was used to assess spatial memory performance and STZ was injected i.c.v., twice, and at the dose of 3 mg/kg, at an interval of 48 h. The results showed that only 24 h SD impaired spatial learning and memory in rats. In addition, 24 h SD attenuated anti-oxidant activity and increased the level of pro-inflammatory markers in the serum. STZ impaired spatial learning and memory, and attenuated anti-oxidant activity and increased the level of pro-inflammatory markers in the serum of rats. Furthermore, 6 h SD slightly and partially improved spatial memory and significantly improved anti-oxidant activity in rats, with no effect on STZ-induced inflammation. We suggest that STZ has more important mechanisms that are involved in its memory impairment effect, and maybe, STZ-induced inflammation has a more important role. We also suggest more detailed studies to investigate the potential therapeutic effect of SD (in different durations) on memory function, oxidative stress, and inflammation.

The altered intrinsic functional connectivity after acupuncture at shenmen (HT7) in acute sleep deprivation.

Introduction: Accumulating evidence has shown that acupuncture could significantly improve the sleep quality and cognitive function of individuals suffering from insufficient sleep. Numerous animal studies have confirmed the effects and mechanisms of acupuncture on acute sleep deprivation (SD). However, the role of acupuncture on individuals after acute SD remains unclear. Methods: In the current study, we recruited 30 healthy subjects with regular sleep. All subjects received resting-state fMRI scans during the rested wakefulness (RW) state and after 24 h of total SD. The scan after 24 h of total SD included two resting-state fMRI sessions before and after needling at Shenmen (HT7). Both edge-based and large-scale network FCs were calculated. Results: The edge-based results showed the suprathreshold edges with abnormal between-network FC involving all paired networks except somatosensory motor network (SMN)-SCN between the SD and RW state, while both decreased and increased between-network FC of edges involving all paired networks except frontoparietal network (FPN)-subcortical network (SCN) between before and after acupuncture at HT7. Compared with the RW state, the large-scale brain network results showed decreased between-network FC in SMN-Default Mode Network (DMN), SMN-FPN, and SMN-ventral attention network (VAN), and increased between-network FC in Dorsal Attention Network (DAN)-VAN, DAN-SMN between the RW state and after 24 h of total SD. After acupuncture at HT7, the large-scale brain network results showed decreased between-network FC in DAN-VAN and increased between-network FC in SMN-VAN. Conclusion: Acupuncture could widely modulate extensive brain networks and reverse the specific between-network FC. The altered FC after acupuncture at HT7 may provide new evidence to interpret neuroimaging mechanisms of the acupuncture effect on acute SD.

An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease.

Sleep apnoea is a highly prevalent disease that often goes undetected and is associated with poor clinical prognosis, especially as it exacerbates many different disease states. However, most animal models of sleep apnoea (e.g., intermittent hypoxia) have recently been dispelled as physiologically unrealistic and are often unduly severe. Owing to a lack of appropriate models, little is known about the causative link between sleep apnoea and its comorbidities. To overcome these problems, we have created a more realistic animal model of moderate sleep apnoea by reducing the excitability of the respiratory network. This has been achieved through controlled genetically mediated lesions of the preBötzinger complex (preBötC), the inspiratory oscillator. This novel model shows increases in sleep disordered breathing with alterations in breathing during wakefulness (decreased frequency and increased tidal volume) as observed clinically. The increase in dyspnoeic episodes leads to reduction in REM sleep, with all lost active sleep being spent in the awake state. The increase in hypoxic and hypercapnic insults induces both systemic and neural inflammation. Alterations in neurophysiology, an inhibition of hippocampal long-term potentiation (LTP), is reflected in deficits in both long- and short-term spatial memory. This improved model of moderate sleep apnoea may be the key to understanding why this disorder has such far-reaching and often fatal effects on end-organ function.

Is Balance Control Affected by Sleep Deprivation? A Systematic Review of the Impact of Sleep on the Control of Balance.

Background: Sleep is a complex physiological function that should be addressed from different perspectives and consider the circadian rhythm. Sleep deprivation, either acute or chronic, negatively affects several functions, including motor control. Balance control is essential in several daily life activities and balance problems are related to falls. Research Question: This review focuses on how sleep conditions impact balance control. Methods: Systematic literature review according to PRISMA guidelines. Results: The literature provided strong evidence that acute sleep deprivation impairs postural control. Chronic sleep deprivation as well as low sleep quality had similar effects, although there is a lower number of works addressing this issue. Furthermore, time awake worsens postural controls and it can be used to detect sleepiness and fatigue. The sleep deprivation showed a stronger negative effect on postural control when removing the visual information (eyes closed) than when reducing proprioceptive feedback (soft surface). There is scarce literature about the effects of chronotype, circadian patterns and chronic sleep deprivation, a frequent problem, on balance control; however they consistently indicate that there is an relationship between them. Most of the studies only consider one-night (acute) sleep deprivation without monitoring prior sleep conditions and the circadian rhythm phase of the participants. However, a few studies indicated that these factors must be considered. Significance: These results suggest that the sleep conditions of a subject should be considered for several days prior to balance control tests. Therefore, we propose a revision of current postural measurement protocols to include sleep assessment, such as sleep quality questionnaires or actimetry, and to consider the circadian rhythm of the participants to plan the hour of the tests.

Meta-Analysis of Sleep Deprivation Effects on Patients With Depression.

Objective: Depression is a common disorder with a high recurrence rate. Since the effect of sleep deprivation on depression in existing studies were inconsistent, the present study aimed to reassess the effects of SD on patients by performing a meta-analysis of updated research. Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched for articles before January 20th, 2021. Data on participant characteristics, SD characteristics, adjunctive method and tests for depression were extracted. A comprehensive analysis was conducted to assess the effect of SD on depression and subgroup analysis was used to determine the sources of heterogeneity. Results: In total, 8 articles were included. An SD time of <7 days slightly worsened depression levels [0.24 (-0.21, 0.69); I 2 = 0%; P = 0.43], a time of 7-14 days had antidepressant effects [-1.52 (-2.07, -0.97); I 2 = 19.6%; P = 0.288], and a time of more than 14 days also worsened depression [0.76 (0.12, 1.40); I 2 = 43.7%; P = 0.169]. Conclusion: SD may serve as an effective antidepressant measure in humans when the time was 7-14 days, while a time of <7 days and more than 14 days worsened depression.

Propofol protects hippocampal neurons in sleep-deprived rats by inhibiting mitophagy and autophagy.

BACKGROUND: Sleep deprivation (SD) causes a disturbance in the cognitive function of rats. While propofol has a powerful sedative and hypnotic effect and is an antioxidant, its effect on the cognitive function of rats following SD remains unknown. The purpose of this study was to explore the protective effects of propofol on excessive autophagy and mitophagy in the hippocampus of rats after SD. METHODS: Adult male rats were intraperitoneally injected with 30 mg/kg of propofol after 96 hours of SD. Then we evaluated the effect of propofol on the cognitive function of sleep deprived rats by the Morris water maze. Transmission electron microscopy, Western blotting, PCR, immunohistochemistry, autophagy enhancer and autophagy inhibitor were used to study the effect of propofol on hippocampal neurons of rat with excessive autophagy and mitophagy. RESULTS: The behavioral experimental results of the Morris water maze showed that propofol improved the learning and memory ability of sleep-deprived rats. The expression of Beclin1, PINK1, parkin, p62, and LC3 protein increased significantly after sleep deprivation. While the intervention of propofol could significantly reduce the expression of these proteins, rapamycin treatment eliminated this effect. CONCLUSIONS: Our findings showed that propofol could reduce the impairment of learning and memory in sleep-deprived rats by inhibiting excessive autophagy and mitophagy in hippocampal neurons. This strategy may provide an application basis for the clinical use of propofol in patients with chronic insomnia.

Effect of Withania Somnifera on the antioxidant and neurotransmitter status in sleep deprivation induced Wistar rats.

Sleep is normally a period of relaxation and repair, important for the maintenance of physiological homeostasis and psychological balance. "Globally, millions of people experiences sleep deprivation daily". Sleep deprivation (SD) impairs cognitive functions, decreases anti-oxidative defense and induces neuronal changes. Withania somnifera (WS), commonly known as an "Indian Ginseng" has broad therapeutic applications, including anti-inflammatory activities, actions on immune system, circulatory system, central nervous system etc., The study is aimed to assess effect of Withania somnifera on antioxidant status and neurotransmitter level in sleep deprivation induced male Wistar albino rats. The study was done in the Department of Physiology, Meenakshi Medical College and Hospital, Enathur, Kanchipuram. 24 male adult Wistar rats weighing 120-150g were used for the study. They were divided into 4 groups with 6 animals in each group. (Group I - cage control, Group II - large platform control, Group III - sleep deprived group and Group IV - WS treated SD group). Animals were deprived sleep for one week using a modified multiple platform method. Oxidative stress parameters and antioxidant enzymes were measured using spectrophotometry. Neurotransmitters such as dopamine and serotonin concentration in the serum were measured by ELISA method. There was a marked (by one-way ANOVA test) decrease observed in the antioxidants enzymes in the cortex of both large platform control and sleep deprivation induced group. The group treated with W. somnifera root extract significantly reduced the free radical production and lipid peroxidation with simultaneous increase in the level of antioxidant enzymes compared to the untreated group. Also in our study the concentration of dopamine and serotonin was found to be significantly reduced (p < 0.05) in sleep deprived (SD) and large platform control group when compared to cage control group. Whereas the group treated with W. somnifera (400mg/kg b.wt) increased the neurotransmitter levels significantly. Withania somnifera proved to be an effective therapeutic agent by maintaining the antioxidant status and neurotransmitter levels.

The protective effect of alpha lipoic acid (ALA) on social interaction memory, but not passive avoidance in sleep-deprived rats.

Sleep is involved in maintaining energy, regulating heat, and recovering tissues. Furthermore, proper cognitive functions need sufficient sleep. Many studies have revealed the impairment effect of sleep deprivation (SD) on cognitive functions including learning and memory. Alpha lipoic acid (ALA) is a potent free radical scavenger, biological antioxidant, and neuroprotective agent. Furthermore, ALA improves learning and memory performance, decreases oxidative stress, and enhances antioxidant biomarkers. In this study, we aimed to investigate the effect of ALA on social interaction and passive avoidance memories in sleep-deprived rats. Total sleep deprivation (TSD) apparatus was used to induce SD (for 24 h). Three-chamber paradigm test and shuttle box apparatus were used to evaluate social interaction and passive avoidance memory, respectively. Rats' locomotor apparatus was used to assess locomotion. ALA was administered intraperitoneally at doses of 17 and 35 mg/kg for 3 consecutive days. The results showed SD impaired both types of memories. ALA at the dose of 35 mg/kg restored social interaction memory in sleep-deprived rats; while, at the dose of 17 mg/kg attenuated impairment effect of SD. Moreover, ALA at the dose of 35 mg/kg impaired passive avoidance memory in sham-SD rats and at both doses did not rescue passive avoidance memory in sleep-deprived rats. In conclusion, ALA showed impairment effect on passive avoidance memory, while improved social interaction memory in sleep-deprived rats.

The role of sleep disturbances in depressive-like behavior with emphasis on α-ketoglutarate dehydrogenase activity in rats.

Sleep disorders may induce anxiety- and depressive-like behaviors. Furthermore, sleep disorders can alter the function of α-KGDH (α-ketoglutarate dehydrogenase), which is involved in the citric acid cycle. In this study, we evaluated the effect of two models of sleep deprivation (SD) including total SD (TSD) and partial SD (PSD), and two models of napping combined with each models of SD on rats' performance in Forced Swim Test (FST) and α-KGDH activity in both hemispheres of the amygdala. 64 male Wistar rats were used in this study. A modified water box was also used to induce SD. The results showed that, immobility was increased in 48-hour PSD group, indicating a possible depressive-like behavior. Swimming time was also increased following 48-hour TSD. However, climbing time was decreased in 48-hour PSD/TSD groups. Additionally, α-KGDH activity was increased in the left amygdala in 48-hour TSD and PSD groups. In conclusion, PSD may increase depressive-like behavior. TSD and PSD can decrease swimming time but increase climbing time, and these effects may be related to serotonergic and noradrenergic transmissions, respectively. Increase in α-KGDH activity in the left amygdala may be related to the brain's need for more energy during prolonged wakefulness. α-KGDH activity in the right amygdala was unaffected probably due to a decrease in alertness following SD.

Ellagic acid protects mice against sleep deprivation-induced memory impairment and anxiety by inhibiting TLR4 and activating Nrf2.

Sleep disorder has become a prevalent issue in current society and is connected with the deterioration of neurobehaviors such as mood, cognition and memory. Ellagic acid (EA) is a phenolic phytoconstituent extracted from grains and fruits that has potent neuroprotective properties. This research aimed to study the alleviative effect and mechanism of EA on memory impairment and anxiety caused by sleep deprivation (SD). EA ameliorated behavioral abnormalities in SD mice, associated with increased dendritic spine density, and reduced shrinkage and loss of hippocampal neurons. EA reduced the inflammatory response and oxidative stress injury caused by SD, which may be related to activation of the Nrf2/HO-1 pathway and mitigation of the TLR4-induced inflammatory response. In addition, EA significantly reduced the mortality and ROS levels in glutamate (Glu)-induced hippocampal neuron injury, and these effects of EA were enhanced in TLR4 siRNA-transfected neurons. However, knockdown of Nrf2 dramatically restrained the protective impact of EA on Glu-induced toxicity. Taken together, EA alleviated memory impairment and anxiety in sleep-deprived mice potentially by inhibiting TLR4 and activating Nrf2. Our findings suggested that EA may be a promising nutraceutical ingredient to prevent cognitive impairment and anxiety caused by sleep loss.

The effect of fish oil on social interaction memory in total sleep-deprived rats with respect to the hippocampal level of stathmin, TFEB, synaptophysin and LAMP-1 proteins.

Fish oil (FO) is one of the richest natural sources of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). DHA is essential for brain functions and EPA has been approved for brain health. On the other hand, stathmin, TFEB, synaptophysin and LAMP-1 proteins are involved in synaptic plasticity, lysosome biogenesis and synaptic vesicles biogenesis. In this study, we aimed to investigate the effect of FO on social interaction memory in sleep-deprived rats with respect to level of stathmin, TFEB, synaptophysin and LAMP-1 in the hippocampus of rats. All rats received FO through oral gavage at the doses of 0.5, 0.75 and 1 mg/kg. The water box was used to induce total sleep deprivation (TSD) and the three-chamber paradigm test was used to assess social behavior. Hippocampal level of proteins was assessed using Western blot. The results showed, FO impaired social memory at the dose of 1 mg/kg in normal and sham groups. SD impaired social memory and FO did not restore this effect. Furthermore, FO at the dose of 0.75 mg/kg decreased social affiliation and social memory in all groups of normal rats, compared with related saline groups, and at the dose of 1 mg/kg impaired social memory for stranger 2 compared with saline group. In sham groups, FO at the dose of 1 mg/kg impaired social memory for stranger 2 compared with saline group. SD decreased hippocampal level of all proteins (except stathmin), and FO (1 mg/kg) restored these effects. In conclusion, FO negatively affects social interaction memory in rats.

Regulation of pro and anti-inflammatory signaling molecules in effect of Withania Somnifera root extract treated sleep deprivation induced Wistar rats.

Sleep plays an imperative role in maintaining good health. Sleep along with circadian cycle wields strong regulatory control over immunity. Sleep deprivation (SD) is a threat to health developing several immunological disorders. The medicinal plant Withania somnifera (WS) root extract is widely used for its immuno-modulatory properties. Therefore, it is of interest to assess the effect of WS root extract on pro and anti-inflammatory signalling in SD rats. 24 male Wistar rats (120-150g) were divided into 4 groups with 6 animals in each. The groups were divided such that Group I - cage control, Group II - large platform control, Group III - sleep deprived & Group IV - WS treated SD rats. RT-PCR based mRNA expression analysis of pro inflammatory (IL-1ß, IL-6, MCP-1, TNF-α) and anti-inflammatory marker (IL-10) in the cortex of control and SD rats were completed. Concurrent protein expression analysis was completed using western blot. Data was analyzed using one-way ANOVA and Duncan's multiple range test in SPSS software version 20. Data showed elevation of pro-inflammatory markers and depression of IL-10. Thus, WS down regulated the pro-inflammatory and up-regulated the anti-inflammatory molecules, which can be further considered towards the treatment of sleep deprivation induced inflammatory diseases.

Cognitive Impairments of Sleep-Deprived Ovariectomized (OVX) Female Rats by Voluntary Exercise.

INTRODUCTION: Previous studies demonstrated that forced and voluntary exercise had ameliorative effects on behavioral tasks followed by Sleep Deprivation (SD) in intact female rats. The main goal of this research was evaluating the impact of voluntary exercise on cognitive functions while SD and ovariectomization is induced in female wistar rats. METHODS: The rats were anesthesized combining dosage of ketamine and xylazine. Then, both ovaries were eliminated and 3 weeks after surgery the animals entered the study. The exercise protocol took 4 weeks of voluntary exercise in a wheel which was connected to home cage. For inducing a 72 hours deprivation the multiple platforms was applied. The cognitive functions were studied by exploiting the Morris Water Maze (MWM) and Novel object recognition tests. Anxiety was evaluated by open field test and corticostrone measurement was carried out by ELISA method. One-way and two-way ANOVA and repeated measures were utilized for data analysis and P<0.05 was considered statistically significant. RESULTS: We observed significant spatial and recognition learning and memory impairments in OVX sleep-deprived rats compared to the control group and voluntary exercise alleviated the SD-induced learning and memory defects. CONCLUSION: We concluded that voluntary exercise can improve cognitive impairments followed by SD in OVX female rats.

Voluntary exercise modulates learning & memory and synaptic plasticity impairments in sleep deprived female rats.

Previous studies have indicated that forced exercise plays a preventive role in synaptic plasticity deficits in the hippocampus and behavioral impairments in sleep-deprived male and female rats. The objective of the present study was to evaluate the effects of voluntary exercise on early long-term potentiation (E-LTP) at the Cornu Ammonis (CA1) area of the hippocampus and behavioral functions by barnes maze and novel location tests in sleep-deprived female rats. Intact female Wistar rats were used in the present study. The exercise protocol was four weeks wheel running and the multiple platform method was applied to induce 72 h Sleep deprivation (SD). We examine the effect of exercise and/or SD on synaptic plasticity using in vivo extracellular recording in the CA1 area of the hippocampus. Spatial learning and memory examined by Barnes maze and recognition memory assessed by novel location test. Field potential recording indicated that the induction and maintenance phase of E-LTP impaired in the sleep deprived animals compared to the other groups. After 72 h SD, LTP impairments were reduced by 4 weeks of voluntary exercise but do not go back to control values. SD impairs learning and memory and exercise could improve these deficits. In conclusion, the synaptic plasticity deficit in sleep-deprived female rats was improved by voluntary exercise. Further studies are suggested to evaluate the possible underlying mechanisms.

Trehalose enhances bone fracture healing in a rat sleep deprivation model.

BACKGROUND: The purpose of this study was to investigate whether sleep deprivation (SD) could delay bone fracture healing and evaluate the therapeutic effect of trehalose. METHODS: Eighteen 300-350 g female Sprague-Dawley rats were created a mid-femoral transverse osteotomy in the right thigh and divided into three groups (i.e., group 1: fracture; group 2: fracture + SD; and group 3: fracture + SD + trehalose). Seven days after surgery, the rats in group 2 and group 3 were started to get sleep-deprived for 18 h per day for 3 weeks. The rats in group 3 were injected with trehalose intraperitoneally at 1 g/kg/d for 3 weeks. Radiological and histological analyses were used to assess fracture healing quality. Circulating cytokines were detected by the end of the study. The expression of M1 and M2 macrophage markers were measured by quantitative real-time polymerase chain reaction (qPCR). RESULTS: X-rays showed group 2 experienced much poorer fracture healing. Micro CT demonstrated that the bone quality of the fracture callus site in group 2 was much worse than that in groups 1 and 3. Both haematoxylin eosin (H&E) and Masson staining revealed that the bone fracture of the group 2 healed worse. Elisa results demonstrated that the interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) of the rats in group 2 were significantly higher. In vitro study showed that 100 mM trehalose enhanced the expression of M2 macrophage markers (Arg-1 and IL-10), and decreased M1 macrophage polarization through the decreasing expression of IL-6. CONCLUSIONS: The present study showed (SD) could delay bone fracture healing in a rat model. And, trehalose could promote the healing of delayed bone fracture union by down-regulating pro-inflammatory mediators and enhancing M2 polarization.