Lateralized brunt of sleep deprivation on white matter injury in a rat model of Alzheimer's disease.

Sleep disturbance is a recognized risk factor for Alzheimer's disease (AD), but the underlying micro-pathological evidence remains limited. To bridge this gap, we established an amyloid-ß oligomers (AßO)-induced rat model of AD and subjected it to intermittent sleep deprivation (SD). Diffusion tensor imaging (DTI) and transmission electron microscopy were employed to assess white matter (WM) integrity and ultrastructural changes in myelin sheaths. Our findings demonstrated that SD exacerbated AßO-induced cognitive decline. Furthermore, we found SD aggravated AßO-induced asymmetrical impairments in WM, presenting with reductions in tract integrity observed in commissural fibers and association fasciculi, particularly the right anterior commissure, right corpus callosum, and left cingulum. Ultrastructural changes in myelin sheaths within the hippocampus and corpus callosum further confirmed a lateralized effect. Moreover, SD worsened AßO-induced lateralized disruption of the brain structural network, with impairments in critical nodes of the left hemisphere strongly correlated with cognitive dysfunction. This work represents the first identification of a lateralized impact of SD on the mesoscopic network and cognitive deficits in an AD rat model. These findings could deepen our understanding of the complex interplay between sleep disturbance and AD pathology, providing valuable insights into the early progression of the disease, as well as the development of neuroimaging biomarkers for screening early AD patients with self-reported sleep disturbances. Enhanced understanding of these mechanisms may pave the way for targeted interventions to alleviate cognitive decline and improve the quality of life for individuals at risk of or affected by AD.

Sleep Deprivation Impairs Intestinal Mucosal Barrier by Activating Endoplasmic Reticulum Stress in Goblet Cells.

Sleep deficiency is associated with intestinal inflammatory conditions and is increasingly recognized as a public health concern worldwide. However, the effects of sleep deficiency on intestinal goblet cells (GCs), which play a major role in intestinal barrier formation, remain elusive. Herein, the effects of sleep deprivation on intestinal GCs were determined using a sleep-deprivation mouse model. Sleep deprivation impaired the intestinal mucosal barrier and decreased the expression of tight junction proteins. According to single-cell RNA sequencing and histologic assessments, sleep deprivation significantly reduced GC numbers and mucin protein levels in intestinal tissues. Furthermore, sleep deprivation initiated endoplasmic reticulum stress by activating transcription factor 6 and binding Ig protein. Treatment with melatonin, an endoplasmic reticulum stress regulator, significantly alleviated endoplasmic reticulum stress responses in intestinal GCs. In addition, melatonin increased the villus length, reduced the crypt depth, and restored intestinal barrier function in mice with sleep deprivation. Overall, the findings revealed that sleep deprivation could impair intestinal mucosal barrier integrity and GC function. Targeting endoplasmic reticulum stress could represent an ideal strategy for treating sleep deficiency-induced gastrointestinal disorders.

Sleep deprivation modulates APOE and LDL receptor-related protein 1 through thyroid hormone T4 and impairs Aß clearance in hippocampus of rats.

Alzheimer's disease is the most common form of dementia. One of its pathological hallmarks is Aß accumulation, which is influenced by APOE genotype and expression, as well as by sleep homeostasis. However, conflicting mechanisms for APOE roles in Aß clearance have been reported, and the relationship between APOE and sleep also remains unclear. In this study, we aimed to investigate how hormonal alteration caused by sleep deprivation affects APOE and its receptors in rats, and to evaluate the role of different cell types in Aß clearance. Paradoxical sleep deprivation for 96 h increased Aß level in hippocampus with concomitant reduction of APOE and LRP1 at the time point within the resting period. Sleep deprivation also significantly reduced T4 levels in both active and resting times. To evaluate the effect of T4 variation, C6 glial cells and primary brain endothelial cells were treated with T4. High T4 level (300 ng/mL) increased APOE, but reduced LRP1 and LDL-R in C6 cells, while in primary endothelial cells, LDL-R levels were increased. Treatment of C6 cells with exogenous APOE reduced LRP1 and Aß uptake. These results suggest that T4 modulates LRP1 and LDL-R in both cell types, but in the opposite manner, thus, sleep deprivation might modify the ratio of the receptors in blood-brain barrier and glial cells by altering T4 levels. Considering that LRP1 and LDL-R are important for Aß clearance, sleep deprivation might also affect the degree of participation of glia in Aß clearance, and consequently, turnover of Aß in the brain.

Sleep deprivation exacerbates microglial reactivity and Aß deposition in a TREM2-dependent manner in mice.

Sleep loss is associated with cognitive decline in the aging population and is a risk factor for Alzheimer's disease (AD). Considering the crucial role of immunomodulating genes such as that encoding the triggering receptor expressed on myeloid cells type 2 (TREM2) in removing pathogenic amyloid-ß (Aß) plaques and regulating neurodegeneration in the brain, our aim was to investigate whether and how sleep loss influences microglial function in mice. We chronically sleep-deprived wild-type mice and the 5xFAD mouse model of cerebral amyloidosis, expressing either the humanized TREM2 common variant, the loss-of-function R47H AD-associated risk variant, or without TREM2 expression. Sleep deprivation not only enhanced TREM2-dependent Aß plaque deposition compared with 5xFAD mice with normal sleeping patterns but also induced microglial reactivity that was independent of the presence of parenchymal Aß plaques. We investigated lysosomal morphology using transmission electron microscopy and found abnormalities particularly in mice without Aß plaques and also observed lysosomal maturation impairments in a TREM2-dependent manner in both microglia and neurons, suggesting that changes in sleep modified neuro-immune cross-talk. Unbiased transcriptome and proteome profiling provided mechanistic insights into functional pathways triggered by sleep deprivation that were unique to TREM2 and Aß pathology and that converged on metabolic dyshomeostasis. Our findings highlight that sleep deprivation directly affects microglial reactivity, for which TREM2 is required, by altering the metabolic ability to cope with the energy demands of prolonged wakefulness, leading to further Aß deposition, and underlines the importance of sleep modulation as a promising future therapeutic approach.

[Effect of chronic sleep deprivation on condylar cartilage in rats].

PURPOSE: The aim of this study was to investigate the morphological changes of condylar cartilage of temporomandibular joint (TMJ) and the expression changes of IL-1ß,TNF-α,IGF-1 and VEGF in condylar cartilage of TMJ by establishing a chronic sleep deprivation model in rats. METHODS: Sixty rats were randomly divided into experimental group, control group and recovery group. Modified multiple platforms method (MMPM) was used to build chronic sleep deprivation models in experimental and recovery groups. Rats in the recovery group received 1 week of cage feeding after sleep deprivation. H-E staining was used to observe morphological change of the condyle. Immunohistochemical method was performed to detect the changes of IL-1ß, TNF-α, IGF-1 and VEGF. The data was processed by using SPSS 23.0 software package. RESULTS: MMPM can establish chronic sleep deprivation model effectively. H-E staining showed condylar cartilage of the experimental group was split stripped, and the boundaries of cartilage cell layer became blurred. Compared with the control group, the recovery group had less cracks in the fibrous layer or some of the cracks were occupied by fibrous tissue. Immunohistochemistry showed that the positive expression intensity of IL-1ß and TNF-α in the experimental group was significantly higher than in the control group (P＜0.05), the positive expression intensity in the recovery group was significantly lower than in the experimental group(P＜0.05). The positive expression intensity of IGF-1 and VEGF in the experimental group was significantly higher than in the control group(P＜0.05). The expression of IGF-1 and VEGF decreased significantly in the recovery group which received sleep deprivation no more than 3 weeks(P＜0.05). CONCLUSIONS: Chronic sleep deprivation can increase the expression of IL-1ß, TNF-α and VEGF in condylar cartilage and aggravate osteoarthritis. Chronic sleep deprivation can lead to increase of IGF-1 in condylar cartilage tissue, which plays a crucial role in protecting and promoting the reconstruction of condylar cartilage. After chronic sleep deprivation, the expressions of IL-1ß, TNF-α, IGF-1 and VEGF in the condylar cartilage of rats were decreased after 1 week of recovery, and the condylar cartilage underwent restorative reconstruction.

Glutamine restores testicular glutathione-dependent antioxidant defense and upregulates NO/cGMP signaling in sleep deprivation-induced reproductive dysfunction in rats.

Oxidative stress has been linked with sleep deprivation (SD)-induced pathological conditions and reproductive dysfunction. On the other hand, glutamine has been established to have antioxidant property. However, the impact of SD, with or without glutamine, on male reproductive function is yet to be elucidated. Thus, this study was designed to investigate the role of SD, with or without glutamine, on male reproductive function and possible associated mechanisms. Ten-week old male Wistar rats weighing 175.6 g± 0.42 were randomly assigned into vehicle that received per os (p.o.) distilled water, glutamine (1 g/kg; po), SD, and SD + glutamine that received treatments as glutamine and SD. Treatment/exposure lasted for 72 h. The results showed that SD led to reduced body weight, seminiferous luminal and epididymal sperm density, low sperm quality, increased testicular and epididymal malondialdehyde, uric acid, DNA fragmentation, and testicular injury markers. In addition, SD caused a reduction in reduced glutathione level and activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione-S-transferase. Also, SD increased tumor necrotic factor-α, interleukin-1ß, and nuclear factor-kappa B levels. Furthermore SD led to impaired libido and erectile dysfunction, and suppression of circulatory nitric oxide, gonadotropins and testosterone, and penile cGMP. However, glutamine attenuated the effects induced by SD. Taken together, the findings of this study demonstrate that SD induces reproductive dysfunction via glutathione-dependent defense depletion and down-regulation of NO/cGMP signaling, which was abolished by glutamine supplementation.

Features of age-related response to sleep deprivation: in vivo experimental studies.

Insomnia is currently considered one of the potential triggers of accelerated aging. The frequency of registered sleep-wake cycle complaints increases with age and correlates with the quality of life of elderly people. Nevertheless, whether insomnia is actually an age-associated process or whether it acts as an independent stress-factor that activates pathological processes, remains controversial. In this study, we analyzed the effects of long-term sleep deprivation modeling on the locomotor and orienting-exploratory activity, spatial learning abilities and working memory of C57BL/6 female mice of different ages. We also evaluated the modeled stress influence on morphological changes in brain tissue, the functional activity of the mitochondrial apparatus of nerve cells, and the level of DNA methylation and mRNA expression levels of the transcription factor HIF-1α (Hif1) and age-associated molecular marker PLIN2. Our findings point to the age-related adaptive capacity of female mice to the long-term sleep deprivation influence. For young (1.5 months) mice, the modeled sleep deprivation acts as a stress factor leading to weight loss against the background of increased food intake, the activation of animals' locomotor and exploratory activity, their mnestic functions, and molecular and cellular adaptive processes ensuring animal resistance both to stress and risk of accelerated aging development. Sleep deprivation in adult (7-9 months) mice is accompanied by an increase in body weight against the background of active food intake, increased locomotor and exploratory activity, gross disturbances in mnestic functions, and decreased adaptive capacity of brain cells, that potentially increasing the risk of pathological reactions and neurodegenerative processes.

Cervical transcutaneous vagal nerve stimulation (ctVNS) improves human cognitive performance under sleep deprivation stress.

Fatigue is a pervasive public health and safety issue. Common fatigue countermeasures include caffeine or other chemical stimulants. These can be effective in limited circumstances but other non-pharmacological fatigue countermeasures such as non-invasive electrical neuromodulation have shown promise. It is reasonable to suspect that other types of non-invasive neuromodulation may be similarly effective or perhaps even superior. The objective of this research was to evaluate the efficacy of cervical transcutaneous vagal nerve stimulation (ctVNS) to mitigate the negative effects of fatigue on cognition and mood. Two groups (active or sham stimulation) of twenty participants in each group completed 34 h of sustained wakefulness. The ctVNS group performed significantly better on arousal, multi-tasking, and reported significantly lower fatigue ratings compared to sham for the duration of the study. CtVNS could be a powerful fatigue countermeasure tool that is easy to administer, long-lasting, and has fewer side-effects compared to common pharmacological interventions.

Senkyunolide I Protects against Sepsis-Associated Encephalopathy by Attenuating Sleep Deprivation in a Murine Model of Cecal Ligation and Puncture.

Sepsis may lead to sleep deprivation, which will promote the development of neuroinflammation and mediate the progression of sepsis-associated encephalopathy (SAE). Senkyunolide I, an active component derived from an herb medicine, has been shown to provide a sedative effect to improve sleep. However, its role in sepsis is unclear. The present study was performed to investigate whether Senkyunolide I protected against SAE in a murine model of cecal ligation and puncture (CLP). Here, we showed that Senkyunolide I treatment improved the 7-day survival rate and reduced the excessive release of cytokines including TNF-α, IL-6, and IL-1ß. A fear conditioning test was performed, and the results showed that Senkyunolide I attenuated CLP-induced cognitive dysfunction. Senkyunolide I treatment also decreased the phosphorylation levels of inflammatory signaling proteins, including p-ERK, p-JNK, p-P38, and p-P65, and the level of inflammatory cytokines, including TNF-α, IL-6, and IL-1ß, in the hippocampus homogenate. Sleep deprivation was attenuated by Senkyunolide I administration, as demonstrated by the modification of the BDNF and c-FOS expression. When sleep deprivation was induced manually, the protective effect of Senkyunolide I against inflammatory responses and cognitive dysfunction was reversed. Our data demonstrated that Senkyunolide I could protect against sepsis-associated encephalopathy in a murine model of sepsis via relieving sleep deprivation.

Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis.

Clonal hematopoiesis, a condition in which individual hematopoietic stem cell clones generate a disproportionate fraction of blood leukocytes, correlates with higher risk for cardiovascular disease. The mechanisms behind this association are incompletely understood. Here, we show that hematopoietic stem cell division rates are increased in mice and humans with atherosclerosis. Mathematical analysis demonstrates that increased stem cell proliferation expedites somatic evolution and expansion of clones with driver mutations. The experimentally determined division rate elevation in atherosclerosis patients is sufficient to produce a 3.5-fold increased risk of clonal hematopoiesis by age 70. We confirm the accuracy of our theoretical framework in mouse models of atherosclerosis and sleep fragmentation by showing that expansion of competitively transplanted Tet2-/- cells is accelerated under conditions of chronically elevated hematopoietic activity. Hence, increased hematopoietic stem cell proliferation is an important factor contributing to the association between cardiovascular disease and clonal hematopoiesis.

Histopathological changes and oxidative damage in type I and type II muscle fibers in rats undergoing paradoxical sleep deprivation.

BACKGROUND: previous studies have shown that muscle atrophy is observed after sleep deprivation (SD) protocols; however, the mechanisms responsible are not fully understood. Muscle trophism can be modulated by several factors, including energy balance (positive or negative), nutritional status, oxidative stress, the level of physical activity, and disuse. The metabolic differences that exist in different types of muscle fiber may also be the result of different adaptive responses. To better understand these mechanisms, we evaluated markers of oxidative damage and histopathological changes in different types of muscle fibers in sleep-deprived rats. METHODS: Twenty male Wistar EPM-1 rats were randomly allocated in two groups: a control group (CTL group; n = 10) and a sleep deprived group (SD group; n = 10). The SD group was submitted to continuous paradoxical SD for 96  h; the soleus (type I fibers) and plantar (type II fiber) muscles were analyzed for histopathological changes, trophism, lysosomal activity, and oxidative damage. Oxidative damage was assessed by lipid peroxidation and nuclear labeling of 8-OHdG. RESULTS: The data demonstrated that SD increased the nuclear labeling of 8-OHdG and induced histopathological changes in both muscles, being more evident in the soleus muscle. In the type I fibers there was signs of tissue degeneration, inflammatory infiltrate and tissue edema. Muscle atrophy was observed in both muscles. The concentration of malondialdehyde, and cathepsin L activity only increased in type I fibers after SD. CONCLUSION: These data indicate that the histopathological changes observed after 96 h of SD in the skeletal muscle occur by different processes, according to the type of muscle fiber, with muscles predominantly composed of type I fibers undergoing greater oxidative damage and catabolic activity, as evidenced by a larger increase in 8-OHdG labeling, lipid peroxidation, and lysosomal activity.

Sleep deprivation aggravates brain injury after experimental subarachnoid hemorrhage via TLR4-MyD88 pathway.

Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular disease, and most of the SAH patients experience sleep deprivation during their hospital stay. It is well-known that sleep deprivation is one of the key components of developing several neurological disorders, but its effect on brain damage after SAH has not been determined. Therefore, this study was designed to evaluate the effect of sleep deprivation using an experimental SAH model in rats. Induction of sleep deprivation for 24 h aggravated the SAH-induced brain damage, as evidenced by brain edema, neuronal apoptosis and activation of caspase-3. Sleep deprivation also worsened the neurological impairment and cognitive deficits after SAH. The results of immunostaining and western blot showed that sleep deprivation increased the activation of microglial cells. In addition, sleep deprivation differently regulated the expression of anti-inflammatory and pro-inflammatory cytokines. The results of immunofluorescence staining and western blot showed that sleep deprivation markedly increased the activation of Toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein 88 (MyD88). Mechanically, treatment with the TLR4 inhibitor TAK-242 or the MyD88 inhibitor ST2825 significantly attenuated the brain damage and neuroinflammation induced by sleep deprivation after SAH. In conclusion, our results indicate that sleep deprivation aggravates brain damage and neurological dysfunction following experimental SAH in rats. These effects were mediated by the activation of the TLR4-MyD88 cascades and regulation of neuroinflammation.

Sleep and sleep deprivation differentially alter white matter microstructure: A mixed model design utilising advanced diffusion modelling.

Sleep deprivation influences several critical functions, yet how it affects human brain white matter (WM) is not well understood. The aim of the present work was to investigate the effect of 32 hours of sleep deprivation on WM microstructure compared to changes observed in a normal sleep-wake cycle (SWC). To this end, we utilised diffusion weighted imaging (DWI) including the diffusion tensor model, diffusion kurtosis imaging and the spherical mean technique, a novel biophysical diffusion model. 46 healthy adults (23 sleep deprived vs 23 with normal SWC) underwent DWI across four time points (morning, evening, next day morning and next day afternoon, after a total of 32 hours). Linear mixed models revealed significant group × time interaction effects, indicating that sleep deprivation and normal SWC differentially affect WM microstructure. Voxel-wise comparisons showed that these effects spanned large, bilateral WM regions. These findings provide important insight into how sleep deprivation affects the human brain.

Caffeine-related effects on cognitive performance: Roles of apoptosis in rat hippocampus following sleep deprivation.

Caffeine is a common stimulant widely existed in food and has stimulatory effects on the central nervous system, shift-work individuals often rely on caffeine to maintain attention and keep awake. Although sleep deprivation (SD) is widely considered as an independent risk factor for cognition retardations, however, little is well understood about the synergistic role of caffeine dosage and SD for cognitive performance. This research intended to investigate the underlying molecular mechanism of varying caffeine doses on cognitive function after sleep deprivation. The results revealed that SD attenuated the cognitive dysfunction, associated with ultrastructure damage and pyramidal neuron loss in the hippocampus, decreased in the level of VIP and AVP. SD also significantly accelerated the neuropeptide-associated apoptosis in the hippocampus, which may modulate via the cAMP-PKA-CREB signal path axis and activation of the downstream apoptosis genes. Additionally, the data indicated that low-dose caffeine (LC) contributed to cognitive enhancement, and high-dose caffeine (HC) aggravated cognitive impairment by modulating hippocampal neuronal apoptosis. Our studies suggest that caffeine, particularly in high dosage, may be a potential factor to influence the neurocognitive outcome caused by sleep loss, and the appropriate amount of caffeine ingested after sleep deprivation deserves serious consideration.

Microglia dynamics in sleep/wake states and in response to sleep loss.

Sleep has an essential role for optimal brain function, but the cellular substrates for sleep regulation are not fully understood. Microglia, the immune cells of the brain, have gained increasingly more attention over the last two decades for their important roles in various brain functions that extend beyond their well-known immune function, including brain development, neuronal protection, and synaptic plasticity. Here we review recent advances in understanding: i) morphological and phenotypic dynamics of microglia including process motility/growth and gene/protein expression, and ii) microglia-neuron interactions including phagocytosis and contact at synapses which alters neuronal circuit activity, both under physiological state in the adult brain. We discuss how the microglia-neuron interactions particularly at synapses could influence microglia and neuronal activities across circadian cycles and sleep/wake states. We also review recent findings on how microglia respond to sleep loss. We conclude by pointing out key questions and proposing suggestions for future research to better understand the role of microglia in sleep regulation, sleep homeostasis, and the function of sleep.

Sleep Apnoea Adverse Effects on Cancer: True, False, or Too Many Confounders?

Obstructive sleep apnoea (OSA) is a prevalent disorder associated with increased cardiovascular, metabolic and neurocognitive morbidity. Recently, an increasing number of basic, clinical and epidemiological reports have suggested that OSA may also increase the risk of cancer, and adversely impact cancer progression and outcomes. This hypothesis is convincingly supported by biological evidence linking certain solid tumours and hypoxia, as well as by experimental studies involving cell and animal models testing the effects of intermittent hypoxia and sleep fragmentation that characterize OSA. However, the clinical and epidemiological studies do not conclusively confirm that OSA adversely affects cancer, even if they hold true for specific cancers such as melanoma. It is likely that the inconclusive studies reflect that they were not specifically designed to test the hypothesis or because of the heterogeneity of the relationship of OSA with different cancer types or even sub-types. This review critically focusses on the extant basic, clinical, and epidemiological evidence while formulating proposed directions on how the field may move forward.

Integrative genomics analysis identifies five promising genes implicated in insomnia risk based on multiple omics datasets.

In recent decades, many genome-wide association studies on insomnia have reported numerous genes harboring multiple risk variants. Nevertheless, the molecular functions of these risk variants conveying risk to insomnia are still ill-studied. In the present study, we integrated GWAS summary statistics (N=386,533) with two independent brain expression quantitative trait loci (eQTL) datasets (N=329) to determine whether expression-associated SNPs convey risk to insomnia. Furthermore, we applied numerous bioinformatics analyses to highlight promising genes associated with insomnia risk. By using Sherlock integrative analysis, we detected 449 significant insomnia-associated genes in the discovery stage. These identified genes were significantly overrepresented in six biological pathways including Huntington's disease (P=5.58 × 10-5), Alzheimer's disease (P=5.58 × 10-5), Parkinson's disease (P=6.34 × 10-5), spliceosome (P=1.17 × 10-4), oxidative phosphorylation (P=1.09 × 10-4), and wnt signaling pathways (P=2.07 × 10-4). Further, five of these identified genes were replicated in an independent brain eQTL dataset. Through a PPI network analysis, we found that there existed highly functional interactions among these five identified genes. Three genes of LDHA (P=0.044), DALRD3 (P=5.0 × 10-5), and HEBP2 (P=0.032) showed significantly lower expression level in brain tissues of insomnic patients than that in controls. In addition, the expression levels of these five genes showed prominently dynamic changes across different time points between behavioral states of sleep and sleep deprivation in mice brain cortex. Together, the evidence of the present study strongly suggested that these five identified genes may represent candidate genes and contributed risk to the etiology of insomnia.

Curcumin prevents neuronal loss and structural changes in the superior cervical (sympathetic) ganglion induced by chronic sleep deprivation, in the rat model.

BACKGROUND: In modern societies, sleep deprivation is a serious health problem. This problem could be induced by a variety of reasons, including lifestyle habits or neurological disorders. Chronic sleep deprivation (CSD) could have complex biological consequences, such as changes in neural autonomic control, increased oxidative stress, and inflammatory responses. The superior cervical ganglion (SCG) is an important sympathetic component of the autonomic nervous system. CSD can lead to a wide range of neurological consequences in SCG, which mainly supply innervations to circadian system and other structures. As the active component of Curcuma longa, curcumin possesses many therapeutic properties; including neuroprotective. This study aimed to evaluate the effect of CSD on the SCG histomorphometrical changes and the protective effect of curcumin in preventing these changes. METHODS: Thirty-six male rats were randomly assigned to the control, curcumin, CSD, CSD + curcumin, grid floor control, and grid floor + curcumin groups. The CSD was induced by a modified multiple platform apparatus for 21 days and animals were sacrificed at the end of CSD or treatment, and their SCGs removed for stereological and TUNEL evaluations and also spatial arrangement of neurons in this structure. RESULTS: Concerning stereological findings, CSD significantly reduced the volume of SCG and its total number of neurons and satellite glial cells in comparison with the control animals (P < 0.05). Treatment of CSD with curcumin prevented these decreases. Furthermore, TUNEL evaluation showed significant apoptosis in the SCG cells in the CSD group, and treatment with curcumin significantly decreased this apoptosis (P < 0.01). This decrease in apoptosis was observed in all control groups that received curcumin. CSD also changed the spatial arrangement of ganglionic neurons into a random pattern, whereas treatment with curcumin preserved its regular pattern. CONCLUSIONS: CSD could potentially induce neuronal loss and structural changes including random spatial distribution in the SCG neurons. Deleterious effects of sleep deprivation could be prevented by the oral administration of curcumin. Furthermore, the consumption of curcumin in a healthy person might lead to a reduction of cell death.

Acute sleep deprivation leads to growth hormone (GH) resistance in rats.

Sleep is an essential physiological process that is required by all higher animals. Sleep has many important physiological functions. Previous studies have focused on the relationship between sleep and growth hormone secretion patterns. However, to date, whether sleep affects the biological activities of GH remains unclear. Here, we investigated this issue by evaluating the growth hormone receptor (GHR)-mediated intracellular signalling pathway in a sleep-deprived rat model. The results showed that GH's signalling ability is decreased in an acute sleep deprivation rat model. JAK2-STAT signalling was decreased significantly compared to that in control rats. We further analysed the possible molecular mechanism of GH signal inhibition in sleep-deprived rats. The results showed that the protein expression levels of SOCS3 (suppressors of cytokine signalling 3, which functions as the negative regulatory molecule of GH's signalling) increased; however, other negative regulatory proteins, such as protein phosphatase (PTP1B), did not change. In addition, acute sleep deprivation results in a significant increase in serum FFA (free fatty acid) level, which is also one of the factors contributing to GH inhibition. These findings suggest that GH signal resistance may be caused by a combination of factors. This study could serve as an important reference for related studies on the effect of sleep deprivation on endocrine systems.

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.