Duration Of Sleep Deprivation Research Articles

Caffeine and modafinil modulate the effects of sleep deprivation on thalamic resting-state functional connectivity: A double-blind pilot study

BackgroundStudies have found that the use of clinically approved caffeine and modafinil can alleviate cognitive impairment due to sleep deprivation (SD) to some extent. However, the neural mechanisms by which these two cognitive enhancers work to counteract the effects of SD on cognitive impairment remain unclear. MethodsA double-blind within-subjects experiment using resting-state functional magnetic resonance imaging (rs-fMRI) was designed. Participants underwent three 36-h SD trials, each of which involved taking 200 mg of caffeine, modafinil, or placebo at the 28th and 32 nd h of SD. Sixteen subregions of the thalamus were selected as the regions of interest and changes in functional connectivity (FC) between the thalamus and the other brain regions were explored after the participants took caffeine or modafinil. ResultsThe subjective sleepiness of the participants increased with the duration of SD. compared with placebo, modafinil and caffeine had insignificant effects on wakefulness or sleepiness. However, in terms of neural FC, we found varying degrees of attenuation or enhancement of the FC between the thalamus and other regions. Taking caffeine during SD weakened the FC between the right rostral temporal thalamus (rTtha) subregion and the left lingual gyrus compared with placebo. Caffeine enhanced the FC between three subregions of the thalamus, namely the left sensory thalamus, the left rTtha, and the right lateral pre-frontal thalamus, and the right inferior temporal, left orbitofrontal, and right superior occipital gyris. Modafinil weakened the FC between the right posterior parietal thalamus and left middle temporal gyrus, and enhanced the FC between the left medial pre-frontal thalamus, left rTtha, and right occipital thalamus and left middle frontal gyrus. ConclusionsAfter 36 h of total SD, modafinil and caffeine administration enhanced or attenuated the time-domain correlations between various subregions of the thalamus and brain regions of the frontal and temporal lobes in healthy adults, compared with placebo. These results provide valuable evidence for further unraveling the neuropharmacological mechanisms of caffeine and modafinil, as well as important insights for exploring effective pharmacological intervention strategies against SD.

Impact of chronic sleep deprivation on male reproductive health: Insights from testicular and epididymal responses in mice.

Sleep deprivation (SD) can cause damage to the male reproductive system. However, the duration required for such damage and the specific sequence and severity of damage to the testis and epididymis remain unclear. To investigate the effects of different durations of SD on different parts of the testis and epididymis caput, corpus, and cauda. Adult ICR mice were randomly assigned to five groups: the SD group (SD for 18h/day for 1, 2, 3, or 4weeks), the SD + Vit E group (supplemented with Vit E 50mg/kg/d during 4weeks of SD, the SD+NS group (saline supplementation during 4weeks of SD), the SD + RS group (5weeks of recovery sleep after 4weeks of SD), and a normal sleep control (Ctrl) group. Following the interventions, sperm parameters, testicular and epididymal histopathology, inflammatory response, and oxidative stress markers were compared between the groups. Compared to the Ctrl group, the SD group showed a decrease in sperm motility and concentration from SD 2W and SD 3W, respectively. Decreases in sperm concentration and motility were more pronounced in the cauda compared to the caput and corpus. Pathological damage was less severe in the epididymis caput than in the corpus and cauda. After 4weeks of SD, inflammation and oxidative stress increased in both testes and epididymis. Both sleep recovery and vitamin E supplementation showed significant improvements, though they did not fully reach the level of the Ctrl group. Chronic SD for more than 2weeks causes varying degrees of damage to the testis, epididymis caput, corpus, and cauda in male mice. This damage is not fully reversible after 5weeks of sleep recovery and antioxidant stress treatment. These findings help us to identify and prevent SD damage to the male reproduction at an early stage.

Abstract Tu063: Acute sleep deprivation induces cardiac remodeling via activation of AT1R/ERK/GSK-3β signaling

Background: Sleep deprivation (SD) has an adverse effect on cardiovascular system. However, whether acute SD contributes to the morphological and functional changes of the heart remains unclear. Approach and Results: The modified multiple platform method (MMPM) was used to establish the SD model in Sprague-Dawley rats. Acute SD significantly enhanced cardiac ejection fraction and fractional shortening in rats as observed by echocardiography. The elevated ratio of heart weight to body weight (HW/BW) and enlarged cross-section area of cardiomyocytes by WGA staining were detected in SD groups (3, 7,10 days). The upregulation of ANP and BNP was also detected by western blotting. Masson-trichrome staining showed significant fibrosis in the SD groups, which was confirmed by western blotting of the fibrosis markers α-SMA and collagen 1. Furthermore, SD increased the level of angiotensin II (Ang II) and angiotensin type 1 receptor (AT1R) in the heart tissue of SD groups accompanied by the activation of the ERK/GSK-3β pathway. Administration of valsartan and benazepril dramatically ameliorated SD-induced cardiac fibrosis and hypertrophy by downregulating Ang II/AT1R and phosphor-ERK/GSK-3β levels. Conclusion: Our results indicated that cardiac remodeling was induced by the acute and short duration of SD, in which the AT1R/ ERK/GSK3β signal pathway was involved. Our study demonstrates a novel complementary phenomenon induced by SD and provides detailed evidence for the risk of SD on the cardiovascular system.

The effects of sleep deprivation on risky decision making.

Sleep deprivation stands as a major threat to both physical and mental well-being, disrupting normal work and life. Given the ubiquity of risky decision making, it is crucial to comprehend how individuals make risky decisions when sleep-deprived. Although research on the effects of sleep deprivation on risky decision making has increased in recent years, it remains limited and lacks a unified conclusion. The current review attempted to elucidate the effects of sleep deprivation on risky decision making in healthy adults and clarify the regulatory mechanisms. The review showed that sleep deprivation had complex effects on risky decision making; that is, whether sleep deprivation led to riskier or more conservative decision-making behavior depended on factors such as sex, gain-loss frame, use of psychotropic drugs, time interval of sleep elimination, duration of sleep deprivation, and others. Additionally, the complexity of these effects might partly arise from the use of different tasks to measure risk-taking behavior. The review also discussed some limitations of existing research and put forth practical recommendations for future studies, aiming to resolve inconsistencies in the effects of sleep deprivation on risky decision making and enhance the ecological validity of conclusions.

The relationship between gut microbiota and inflammatory response, learning and memory in mice by sleep deprivation.

Sleep deprivation has developed into a common phenomenon, which can lead to inflammatory responses and cognitive impairment, but the underlying mechanism is ambiguous. Emerging evidence shows that gut microbiota plays a crucial role in theoccurrence and development of inflammatory and psychiatric diseases, possibly through neuroinflammation and the brain-gut axis. The current study investigated the influence of sleep deprivation on gut microbiota composition, pro-inflammatory cytokines, learning and memory in mice. Further, it explored whether changes in gut microbiota increase pro-inflammatory cytokine and induce learning and memory impairment. Healthy 8-week-old male C57BL/6J mice were randomly divided into the regular control group (RC), environmental control group (EC), and sleep deprivation group (SD). The sleep deprivation model was established by the Modified Multiple Platform Method. The experimental mice were subjected to sleep deprivation for 6h/d (8:00 am∼14:00 pm) in a sleep deprivation chamber, and the duration of sleep deprivation was 8 weeks. Morris water maze test to assess learning and memory in mice. Enzyme-Linked Immunosorbent Assay determined the concentrations of inflammatory cytokines. The changes in gut microbiota in mice were analyzed by 16S rRNA sequencing. We found that SD mice had elevated latency of exploration to reach the hidden platform (p>0.05) and significantly decreased traversing times, swimming distance, and swimming time in the target zone when the hidden platform was removed (p<0.05). Sleep deprivation caused dysregulated expression in serum IL-1β, IL-6, and TNF-α in mice, and the difference was significant (all p<0.001). Tannerellaceae, Rhodospirillales, Alistipes, and Parabacteroides were significantly increased in SD mice. Correlation analysis showed IL-1β was positively correlated with the abundance of Muribaculaceae (r=0.497, p<0.05) and negatively correlated with the abundance of Lachnospiraceae (r=-0.583, p<0.05). The TNF-α was positively correlated with the abundances of Erysipelotrichaceae, Burkholderiaceae, and Tannerellaceae (r=0.492, r=0.646, r=0.726, all p<0.05). Sleep deprivation can increase pro-inflammatory cytokine responses and learning and memory impairment in mice and may be caused by the disorder of the microbiota. These findings of this study may open avenues for potential interventions that can relieve the detrimental consequences of sleep loss.

Effect of sleep deprivation and daylight restriction on the immune response to Escherichia coli-induced septicemia in Wistar rats

ABSTRACT Circadian rhythms influence the immune response. Its disruption can therefore alter the immune response of the host to pathogens. This study was designed to investigate the effects of two circadian disruptors, sleep-deprivation (SD) and daylight-restriction (DLR), on the immune response to septicemia which was induced using low-dose Escherichia coli (0.1 mL i.p.) (ECIS). Forty-eight Wistar rats (150–180 g) were grouped into six (n = 8): I(control), II(control+ECIS), III(SD12hrs+ECIS), IV(SD96hrs+ECIS), V(DLR12hrs+ECIS), and VI(DLR96hrs+ECIS) respectively. Following either SD or DLR in experimental groups, ECIS was induced and systemic immune response was evaluated after 7 days. Innate (leucocytes, eosinophils, IFN-γ and TNF-α) and adaptive (immunoglobulin -G and -M) immune responses was altered in short and long-term sleep deprived ECIS groups while only innate immune responses were impaired in the short-term daylight-restricted group. Spleen histology exhibited pathologies that worsened with increasing durations of SD and DLR. In conclusion, the immune response in Wistar rats to systemic infection is weakened to a greater extent by sleep-deprivation than by daylight-restriction.

NREM sleep loss increases neurofilament light chain levels in APP/PS1 and C57BL/6J mice.

Sleep disturbances exacerbate the progression of Alzheimer's disease (AD), but disturbances of non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep may have different effects. Neurofilament light chain (NfL), an axon-specific protein, is an indicator of the severity of neuronal apoptosis. To investigate whether or notNREM or REM sleep is crucial to neuronal survival, we examined the effects of induced NREM or REM sleep loss on NfL levels in APP/PS1 mice, a model of AD, and their wild-type (WT) C57BL/6J littermates. At 6months of age, WT mice and AD mice were equally divided into six groups, namely, the WT-normal sleep (S), WT-total sleep deprivation (TSD), WT-REM deprivation (RD), AD-S, AD-TSD and AD-RD groups, according to the type of sleep intervention applied. All mice underwent 6days of sleep intervention. Cerebrospinal fluid (CSF) and plasma NfL levels were measured at baseline and on days 2, 4 and 6, and spatial memory was assessed in the Morris water maze (MWM) test. Among the 18 WT and 18 AD mice,CSF and plasma NfL levels were higher in AD-TSD mice than in AD-S or AD-RD mice, while no significant difference was observed between the latter two groups. In AD-TSD mice, CSF and plasma NfL levels increased with the duration of sleep deprivation. A similar pattern of results was observed for the WT groups. NREM sleep loss may increase CSF and plasma NfL levels in both WT and AD mice.

Mapping recovery from sleep deprivation

Sleep timing is based on the interactions between circadian and homeostatic processes. However, sleep deprivation perturbs the time of sleep onset, and the timing and duration of the following recovery sleep may differ from that of baseline sleep. Here we show that the responses to 0–24 h of sleep deprivation can be approximated by a one-dimensional, discontinuous map computed from a physiologically-based ordinary differential equation model for human sleep-wake regulation. The map relates the circadian phase of sleep onset to the circadian phase of the previous sleep onset and reproduces sleep patterns seen in experimental data for the timing and duration of recovery sleep when sleep onset occurs 8 or 20 h after the usual sleep onset. In addition, the durations of recovery sleep predicted by the map for sleep deprivations of 0 to 24 h are consistent with numerical simulations of recovery sleep using the full (nonautonomous, 8-dimensional) model. Our results demonstrate that the circadian phase of sleep onset affects the duration of recovery sleep more strongly than the homeostatic sleep drive for most durations of sleep deprivation. In addition, the map establishes a lower bound for the length of recovery sleep. As a result, the map provides a computationally-efficient way of incorporating sleep dynamics into new technologies that allow users to predict the effects of sleep deprivation and identify optimal sleep schedules.

Chronic REM-sleep deprivation induced laryngopharyngeal reflux in rats: A preliminary study

ObjectiveThe aim of this study was to investigate the relationship of chronic REM-sleep deprivation with laryngopharyngeal reflux (LPR) and its mechanism. MethodsForty healthy male SD rats (body weight 250–280 g) were randomly divided into four groups. The first three ones were test group, which underwent REM-sleep deprivation with different duration of time by modified multiplatform water surface method. The last group was the control one having normal sleep. All the animals were performed Dx-pH monitoring when finishing sleep deprivation, and sacrificed to study the gastric residual rate (GRR) and small intestine peristalsis (SPR) rate by charcoal meal method. ResultsAt prone position, the reflux incidence in the test groups fairly increased with the duration of sleep deprivation (p<0.05). The total number of reflux episodes at prone position in the test group rats with 3 months duration of sleep deprivation was significantly increased compared with that in the control ones (p<0.05). GRR in rats experiencing sleep deficiency for different duration all reduced significantly when compared to the control group (p<0.05). GRR and SPR presented continuous decline tendency with the duration of sleep deprivation (p>0.05). ConclusionsIt is suggested that chronic sleep deficiency could cause LPR in rats, which might result from the uncoordinated digestive tract motility caused by dysfunction of central nervous system after chronic REM-sleep deprivation. Our results implied that chronic REM-sleep deprivation might be one of the causes of LPR. Addressing sleep problems might help to decrease the prevalence of LPR and enhance its treatment efficacy.

Free Radical Oxidation and Sleep Disorders in Andro- and Menopause (Literature Review)

This review presents data on changes in the physiology of sleep during reproductive aging. It is noted that insomnia and obstructive sleep apnea syndrome (OSAS) are the main sleep disorders. The results of foreign and domestic studies in the field of free radical oxidation during sleep deprivation in animal models are presented, indicating the dependence of processes on the duration of sleep deprivation. The largest number of studies of free radical processes in a person with somnological pathology was carried out in the study of OSAS. Blood, urine, saliva, condensate of exhaled air can be biomaterial for determining the parameters of free radical oxidation. It was shown that the intensity of oxidative stress depends on the severity of OSAS, as evidenced by the positive correlation of the level of active products of thiobarbituric acid, the products of oxidation of proteins and carbonyl groups with the apnea/hypopnea index, determining the development of not only oxidative, but also carbonyl stress in patients with a severe degree OSAS. Biomarkers such as thioredoxin, malondialdehyde, superoxide dismutase, and reduced iron have shown a more stable relationship between increased oxidative stress and OSA. Despite the results obtained, the question of the association of oxidative stress and hypoxia in OSA remains debatable, which is associated with the opposite results of some studies. Insomnia, which occurs mainly in females, is accompanied by a high level of end products of lipid peroxidation with a decrease in the activity of antioxidants such as paraoxonase, an enzymatic component of the glutathione system. Along with this, menopausal women present low levels of uric acid, which correlates with high scores of the Pittsburgh sleep quality index questionnaire. Recent studies have identified an association between the activity of the «lipoperoxidation – antioxidants» system and the Clock 3111T/C gene polymorphism in menopausal Caucasian women, indicating the protective role of the minor allele.

Sleep deprivation disrupts the lacrimal system and induces dry eye disease

Sleep deficiency is a common public health problem associated with many diseases, such as obesity and cardiovascular disease. In this study, we established a sleep deprivation (SD) mouse model using a ‘stick over water’ method and observed the effect of sleep deficiency on ocular surface health. We found that SD decreased aqueous tear secretion; increased corneal epithelial cell defects, corneal sensitivity, and apoptosis; and induced squamous metaplasia of the corneal epithelium. These pathological changes mimic the typical features of dry eye. However, there was no obvious corneal inflammation and conjunctival goblet cell change after SD for 10 days. Meanwhile, lacrimal gland hypertrophy along with abnormal lipid metabolites, secretory proteins and free amino-acid profiles became apparent as the SD duration increased. Furthermore, the ocular surface changes induced by SD for 10 days were largely reversed after 14 days of rest. We conclude that SD compromises lacrimal system function and induces dry eye. These findings will benefit the clinical diagnosis and treatment of sleep-disorder-related ocular surface diseases.

5. Sleep deprivation in the activation of interictal spikes and epileptic seizures

Objective To describe and review the use of sleep deprived EEG in the activation of interictal spikes and epileptic seizures. Background Sleep deprivation (SD) has been used to enhance EEG sensitivity in the diagnosis of epilepsy. However, standardized guidelines for the use of SD-EEGs are lacking. Here, we provide an update in the literature of sleep SD-EEG and epilepsy as well as presenting data from a retrospective study. Design/methods A literature search using PubMed was carried out to identify papers focusing on sleep deprivation EEG and interictal discharges. A total of 39 abstracts were obtained, 13 were screened and included in this review. We also present data from a retrospective study of 156 patients that were assessed with a short and long-monitoring EEG as well as SD-EEG at Son Espases Hospital (Spain) and evaluated their sensitivity in the diagnosis of interictal discharges in patients with suspected epilepsy. Results Further studies are needed to evaluate the role of SD-EEG in patients with suspected epilepsy. In our retrospective study 21% of patients with a previous normal awake EEG showed interictal discharges in the SD-EEG. Conclusions Some studies have shown that SD-EEG increases sensitivity and specificity diagnosing interictal activity. However, the duration of sleep deprivation and length of the test varies according to the different studies. The role of SD-EEG should be further evaluated. The use of subtemporal electrodes may contribute to the diagnosis of temporal lobe epileptiform focus.

Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron.

Military personnel are often subjected to sleep deprivation (SD) during combat operations. Since SD is a severe stress and alters neurochemical metabolism in the brain, a possibility exists that acute or long-term SD will influence blood-brain barrier (BBB) function and brain pathology. This hypothesis was examined in young adult rats (age 12 to 14 weeks) using an inverted flowerpot model. Rats were placed over an inverted flowerpot platform (6.5 cm diameter) in a water pool where the water levels are just 3 cm below the surface. In this model, animals can go to sleep for brief periods but cannot achieve deep sleep as they would fall into water and thus experience sleep interruption. These animals showed leakage of Evans blue in the cerebellum, hippocampus, caudate nucleus, parietal, temporal, occipital, cingulate cerebral cortices, and brain stem. The ventricular walls of the lateral and fourth ventricles were also stained blue, indicating disruption of the BBB and the blood-cerebrospinal fluid barrier (BCSFB). Breakdown of the BBB or the BCSFB fluid barrier was progressive in nature from 12 to 48 h but no apparent differences in BBB leakage were seen between 48 and 72 h of SD. Interestingly, rats treated with metal nanoparticles, e.g., Cu or Ag, showed profound exacerbation of BBB disruption by 1.5- to 4-fold, depending on the duration of SD. Measurement of plasma and brain serotonin showed a close correlation between BBB disruption and the amine level. Repeated treatment with the serotonin 5-HT3 receptor antagonist ondansetron (1 mg/kg, s.c.) 4 and 8 h after SD markedly reduced BBB disruption and brain pathology after 12 to 24 h SD but not following 48 or 72 h after SD. However, TiO2-nanowired ondansetron (1 mg/kg, s.c) in an identical manner induced neuroprotection in rats following 48 or 72 h SD. However, plasma and serotonin levels were not affected by ondansetron treatment. Taken together, our observations are the first to show that (i) SD could induce BBB disruption and brain pathology, (ii) nanoparticles exacerbate SD-induced brain damage, and (iii) serotonin 5-HT3 receptor antagonist ondansetron is neuroprotective in SD that is further potentiated byTiO2-nanowired delivery, not reported earlier.

Short-term sleep deprivation stimulates hippocampal neurogenesis in rats following global cerebral ischemia/reperfusion.

BackgroundSleep deprivation (SD) plays a complex role in central nervous system (CNS) diseases. Recent studies indicate that short-term SD can affect the extent of ischemic damage. The aim of this study was to investigate whether short-term SD could stimulate hippocampal neurogenesis in a rat model of global cerebral ischemia/reperfusion (GCIR).MethodsOne hundred Sprague-Dawley rats were randomly divided into Sham, GCIR and short-term SD groups based on different durations of SD; the short-term SD group was randomly divided into three subgroups: the GCIR+6hSD*3d-treated, GCIR+12hSD-treated and GCIR+12hSD*3d-treated groups. The GCIR rat model was induced via the bilateral occlusion of the common carotid arteries and hemorrhagic hypotension. The rats were sleep-deprived starting at 48 h following GCIR. A Morris water maze test was used to assess learning and memory ability; cell proliferation and differentiation were analyzed via 5-bromodeoxyuridine (BrdU) and neuron-specific enolase (NSE), respectively, at 14 and 28 d; the expression of hippocampal BDNF was measured after 7 d.ResultsThe different durations of short-term SD designed in our experiment exhibited improvement in cognitive function as well as increased hippocampal BDNF expression. Additionally, the short-term SD groups also showed an increased number of BrdU- and BrdU/NSE-positive cells compared with the GCIR group. Of the three short-term SD groups, the GCIR+12hSD*3d-treated group experienced the most substantial beneficial effects.ConclusionsShort-term SD, especially the GCIR+12hSD*3d-treated method, stimulates neurogenesis in the hippocampal dentate gyrus (DG) of rats that undergo GCIR, and BDNF may be an underlying mechanism in this process.

Blood-gene expression reveals reduced circadian rhythmicity in individuals resistant to sleep deprivation.

To address whether changes in gene expression in blood cells with sleep loss are different in individuals resistant and sensitive to sleep deprivation. Blood draws every 4 h during a 3-day study: 24-h normal baseline, 38 h of continuous wakefulness and subsequent recovery sleep, for a total of 19 time-points per subject, with every 2-h psychomotor vigilance task (PVT) assessment when awake. Sleep laboratory. Fourteen subjects who were previously identified as behaviorally resistant (n = 7) or sensitive (n = 7) to sleep deprivation by PVT. Thirty-eight hours of continuous wakefulness. We found 4,481 unique genes with a significant 24-h diurnal rhythm during a normal sleep-wake cycle in blood (false discovery rate [FDR] < 5%). Biological pathways were enriched for biosynthetic processes during sleep. After accounting for circadian effects, two genes (SREBF1 and CPT1A, both involved in lipid metabolism) exhibited small, but significant, linear changes in expression with the duration of sleep deprivation (FDR < 5%). The main change with sleep deprivation was a reduction in the amplitude of the diurnal rhythm of expression of normally cycling probe sets. This reduction was noticeably higher in behaviorally resistant subjects than sensitive subjects, at any given P value. Furthermore, blood cell type enrichment analysis showed that the expression pattern difference between sensitive and resistant subjects is mainly found in cells of myeloid origin, such as monocytes. Individual differences in behavioral effects of sleep deprivation are associated with differences in diurnal amplitude of gene expression for genes that show circadian rhythmicity.

Effect of short-duration sleep deprivation on the vestibulo-ocular reflex system evaluated by ocular vestibular-evoked myogenic potential test

Conclusion: The ocular vestibular-evoked myogenic potential (oVEMP) test yields the same information as the rotational test in sleep-deprived subjects as evidenced by increased vestibulo-ocular reflex (VOR) asymmetry. However, the duration of sleep deprivation (12 h) and testing time required for the oVEMP test are shorter than for the rotational test. Objective: This study utilized the oVEMP test in sleep-deprived subjects to investigate the effect of short-duration sleep deprivation on the VOR system. Methods: Twenty healthy resident physicians underwent oVEMP and cervical VEMP (cVEMP) tests twice in a randomized order; one test battery was performed after a normal sleep, and the other was performed after a night duty at the emergency service, which meant a state of 12 h sleep deprivation. Results: All 20 subjects had clear oVEMPs regardless of whether testing was performed after a normal sleep or 12 h sleep deprivation condition. Significant differences were not identified between the two sleep conditions in terms of characteristic parameters, i.e. latencies and amplitude of oVEMPs. However, the mean asymmetry ratio after sleep deprivation (20 ± 13%) was significantly larger than that after normal sleep (8 ± 12%). Conversely, the cVEMP parameters did not differ significantly between the two sleep conditions.

Role for neuronal nitric oxide synthase in sleep homeostasis and arousal

The function of sleep remains one of the mysteries of the ages, yet sleep is an evolutionarily preserved behavior manifest in diverse organisms including worms (1), flies (2), and all vertebrates thus far examined (3). Perhaps one of the most compelling arguments for a sleep function is its homeostatic control. In everyday language, this homeostasis usually refers to the tendency to sleep deeply after staying awake for a long period and, after sleeping over a long period, to stay awake. The mechanisms responsible for sleep homeostasis are likely to be intimately related to sleep function and therefore worthy of investigation. Morairty et al. (4) argue that a subset of interneurons expressing neuronal NOS (nNOS) and the substance P receptor [neurokinin-1 receptor (NK1)] is responsible for the link between sleep deprivation (SD)-induced “homeostatic sleep drive” and increased EEG slow wave activity (SWA). SWA is considered an index of the depth or efficacy of sleep as further discussed below. With increasing duration of SD, from 2 to 6 h, activity of these cortical nNOS neurons, assessed by Fos expression 2 h into the ensuing recovery sleep, increases in association with increasing SWA. In nNOS KO mice, the SWA homeostatic sleep response is attenuated, suggesting a role for nNOS in sleep homeostasis. The authors hypothesize that in WT mice, these cortical nNOS/NK1 neurons release NO in a Fos-marked, activity-dependent manner to elicit the SWA homeostatic sleep response. Somewhat surprisingly, in the nNOS KO mutants, the increased activity of nNOS neurons in response to SD (marked by Fos in NK1 neurons) remains unaffected. This implies that …

Influence of sleep deprivation on expression of MKK4 and c-fos in the mandibular condylar cartilage of rats

The aim of this study was to investigate the changes in expression of mitogen-activated protein kinase kinase 4 (MKK4) and c-fos in the mandibular condylar cartilage of rats that had been subjected to sleep deprivation. One hundred and twenty female Wistar rats were randomly divided into 6 groups with 20 in each: sleep deprivation for 2 days, 4 days, 6 days, and 8 days, large-platform controls, and cage controls. After sleep deprivation by the modified multiple platform method the sleep-deprived rats were killed. The large-platform and cage control rats were killed at the same time as the rats deprived of sleep for 8 days. Haematoxylin and eosin were used to record the morphological changes in cartilage, and immunohistochemistry and real-time quantitative polymerase chain reaction (PCR) were used to detect the expression of MKK4 and c-fos. Pathological alterations were apparent after 6 and 8 days of sleep deprivation. Compared with control groups, the expression of MKK4 in the sleep-deprived groups was lower, while that of c-fos was higher. As the duration of sleep deprivation increased, the expression of MKK4 decreased. These results indicate that the variation in expression of MKK4 and c-fos may be correlated with pathological changes induced by sleep deprivation in mandibular condylar cartilage in rats.

Sleep Homeostasis: Finding Odysseus among the Mnesteres

Sleep Homeostasis: Finding Odysseus among the Mnesteres

Short-term sleep deprivation may alter the dynamics of hippocampal cell proliferation in adult rats

Long-term (>48 h) sleep deprivation (SD) reduces adult rat hippocampal cell proliferation and neurogenesis, yet reported effects of short-term (<24 h) SD are inconsistent. We systematically assessed the effects of various durations of SD on adult rat hippocampal cell proliferation. Rats were sleep-deprived for 6, 12, 24, 36 or 48 h and injected with 5-bromo-2′-deoxyuridine (BrdU) 2 h before the end of SD. Immunolabeling for BrdU in the hippocampal subgranular zone increased significantly after 12 h SD but tended to decrease after 48 h SD relative to respective Controls. Surprisingly, SD did not alter immunolabeling for Ki67 protein (Ki67) or proliferating cell nuclear antigen (PCNA), two intrinsic cell proliferation markers. SD did not affect BrdU or Ki67 labeling in the subventricular zone, nor did it affect serum corticosterone levels. Because immunoreactivity for Ki67 and PCNA can identify cells in all phases of the ∼25 h cell cycle in adult rat hippocampus, whereas BrdU labels only cells in S-phase (∼9.5 h), this discrepancy suggests that 12 h SD might have affected cell cycle dynamics. A separate group of rats were injected with BrdU 10 h before the end of 12 h SD, which would allow some time for labeled cells to divide; the results were consistent with an acceleration of the timing of hippocampal progenitor cell division during 12 h SD. These results suggest that short-term (12 h) SD transiently produces more hippocampal progenitor cells via cell cycle acceleration, and confirm the importance of using multiple cell cycle markers or BrdU injection paradigms to assess potential changes in cell proliferation.