Essence of Chicken Supplementation Alters Brain and Blood Metabolite Signatures in Sleep-Deprived Mice

Acute 2-phenyl-3-(phenylselanyl)benzofuran treatment reverses the neurobehavioral alterations induced by sleep deprivation in mice

Activities of Monoamine Oxidase (MAO) A and B in Discrete Regions of Rat Brain After Rapid Eye Movement (REM) Sleep Deprivation

Sleep deprivation decreases phase-shift responses of circadian rhythms to light in the mouse: role of serotonergic and metabolic signals

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Caffeine and sleep-deprivation mediated changes in open-field behaviours, stress response and antioxidant status in mice

Metabotropic Glutamate Receptors of Subtype 5 (mGluR5) and Sleep Homeostasis: Effects of Gene Knock-out and of Selective Negative Allosteric Modulation on EEG, Behavioral and Molecular Variables in Mice

Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.

Integrated metabolomics and proteomics analysis reveals energy metabolism disorders in the livers of sleep-deprived mice

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

We did a comparative analysis of the gene expression profiles of the hippocampus from sleep deprivation and Alzheimer’s disease (AD) mice. Differentially expressed genes (DEGs) were identified by comparing the transcriptome profiles of the hippocampus of sleep deprivation or AD mouse models to matched controls. The common DEGs between sleep deprivation and AD were identified by the overlapping analysis, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The results showed that a total of 16 common DEGs showed similar change patterns in both sleep deprivation mice and AD mice. Sgk1, Ly6a, Atp6v0e, Hspb8, Htra1, Pdk4, Pfkfb3, Golm1, and Plin3 were up-regulated in the two disorders, whereas, Marcksl1, Fgd1, Scarb1, Mvd, Klhl13, Elovl2, and Vps29 were down-regulated. Acetyl-CoA metabolic process and lipid biosynthetic process were significantly enriched by those DEGs. The highly expressed DEGs and the two GO terms were associated with neuropathological changes according to the previous studies. As expected, sleep deprivation may contribute the AD development through these common DEGs.

Introduction Alzheimer's disease (AD), the most common form of dementia in the US, affecting 6.5 million individuals with a total healthcare cost of $321 billion, is characterized by cognitive dysfunction, memory problems, and disrupted sleep. Mice are crucial for studying AD and sleep patterns in humans, but current methods for inducing sleep disruption have limitations such as wired telemetry, real-time monitoring challenges, and disrupting the mouse's home environment. Better tools are needed to maximize the potential of mouse models in AD and sleep research. Objectives: This study aims to fill this gap by developing a novel system of sleep deprivation in mice to explore the underlying mechanisms connecting sleep and AD. Methods This study utilized a combination of DSI Co. wireless telemetry, Spike-2 software from CED Co., and third-party olfactory controllers to achieve automatic sleep deprivation via air-puffs. C57BL/6J (B6) mice were utilized for validation of the behavioral state recording/sleep deprivation system and preliminary biological analyses. The system was employed to achieve sleep deprivation in mice for 9 hours, then blood and brain tissue were collected for subsequent genetic analysis. qPCR was then applied to determine the expression of genes of interest related to AD, which was utilized in combination with analysis of variance to elucidate significance. Results Behavioral state recordings indicate the system can accurately collect and analyze telemetry signals in real time then initiate an air-puff, which successfully wakes the animal. qPCR results indicate a significant decrease in DNA damage repair enzyme and an increase in inflammatory cytokine gene expression, relative to controls, following ~9 hours of sleep deprivation (p&amp;lt; 0.05). These results collectively indicate the progression of an AD-phenotype. Conclusion These preliminary results indicate this novel system of behavioral state recording and sleep deprivation in mice can be applied to successfully explore the underlying mechanisms connecting sleep and AD. Future studies will extend to further proteomic and epigenetic analyses and explore specific sleep stages in relation to AD-progression. Support (if any) Center for Therapeutic Innovation (CTI)

Voluntary exercise ameliorates synaptic pruning deficits in sleep-deprived adolescent mice

To evaluate whether induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex after stimulation of the right maxillary canine and to examine whether these metabolic changes and the subjective pain intensity perception correlate. Ten male volunteers were included in the pain group and compared with a control group of 10 other healthy volunteers. The pain group received a total of 87-92 electrically induced pain stimuli over 15 min to the right maxillary canine tooth. Contemporaneously, they evaluated the subjective pain intensity of every stimulus using an analogue scale. Neurotransmitter changes within the left insular cortex were evaluated by MR spectroscopy. Significant metabolic changes in glutamine (+55.1%), glutamine/glutamate (+16.4%) and myo-inositol (-9.7%) were documented during pain stimulation. Furthermore, there was a significant negative correlation between the subjective pain intensity perception and the metabolic levels of Glx, Gln, glutamate and N-acetyl aspartate. The insular cortex is a metabolically active region in the processing of acute dental pain. Induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex resulting in significant alterations in metabolites. Negative correlation between subjective pain intensity rating and specific metabolites could be observed.

Background: Sleep deprivation (SD), defined as the disruption or loss of normal sleep, negatively affects energy metabolism, immune function, and gut microbiota in both humans and animals. Although SD has detrimental effects, it is often unavoidable due to work or study demands. Exercise has been shown to improve sleep quality, regulate metabolism, and enhance immune function. However, whether exercise can mitigate the adverse effects of unavoidable SD remains unclear. Methods: To explore the protective effects of exercise against SD-induced gut microbiota and metabolic dysfunction, mice were randomly assigned to four groups: control (CTR), exercise (EXE), SD, and exercise + SD (EXE + SD). Inflammatory markers and gut microbiota composition were analyzed to assess the impacts of SD and exercise interventions. Results: The inflammatory levels and energy metabolism in SD mice were significantly increased compared to those in CTR mice. Compared with SD mice, EXE + SD mice had a more stable gut microbiota structure and higher butyrate levels. Meanwhile, the inflammatory response caused by SD was also inhibited by exercise preconditioning. Both lipopolysaccharide inhibitors injection and butyrate supplementation can partially alleviate the elevation of inflammatory response and energy metabolism caused by SD. Conclusion: The inflammation and energy metabolism disorders in mice caused by SD can be inhibited by exercise preconditioning through stabilizing the structure of gut microbiota. This protective effect is highly likely related to the increase in butyric acid levels caused by exercise.

100. Effects of waking drug, modafinil on cognitive function and neuro-immune interaction in mice with sleep deprivation