Paradoxical Sleep Deprivation Research Articles

Electroacupuncture alleviates paradoxical sleep deprivation-induced postoperative hyperalgesia via a7nAChR mediated BDNF/TrkB-KCC2 signaling pathway in the spinal cord

Perioperative Paradoxical sleep deprivation (PSD) is associated with postoperative hyperalgesia. However, the clinical therapeutic strategies for PSD-induced postoperative hyperalgesia are limited. Electroacupuncture (EA) has been used for attenuating many types of pain, including neuropathic pain and inflammatory pain, but its effect on PSD-induced postoperative hyperalgesia is still unclear, and its analgesia mechanism should be further explored. In this study, we designed to investigate the possible mechanism of PSD-induced postoperative hyperalgesia and the effect of EA on PSD-induced postoperative hyperalgesia, and whether the mechanism is related to the BDNF/TrkB signaling pathway mediated by α7nAChR in the spinal cord. The paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) of rats were used to detect PSD-induced hyperalgesia. The expression of α7nAChR, BDNF, TrkB and KCC2 in the spinal cord were evaluated by Western blot and immunofluorescence. The results showed that preoperative 24h PSD significantly decreased the PWTL and PWMT. The expression of α7nAChR and KCC2 significantly downregulated in the spinal cord of PSD-induced postoperative hyperalgesia rats, the opposite was observed for BDNF and TrkB expression. Moreover, intrathecal injection of alpha-bungarotoxin (α-BGT), a selective antagonist for α7nAChR, not only aggravated the pain hypersensitivity, but also demonstrated a further decrease of α7nAChR and KCC2 expression and a further increase of BDNF and TrkB expression. EA stimulation increased the PWTL and PWMT values of PSD-induced postoperative hyperalgesia rats, significantly upregulated α7nAChR and KCC2 expression, and significantly downregulated BDNF and TrkB expression. Moreover, intrathecal injection of α-BGT suppressed the analgesic effect of EA, inhibited the enhancement of α7nAChR and KCC2 expression and the reduction of BDNF and TrkB expression induced by EA. In conclusion, our study indicated that 24h PSD can cause postoperative hyperalgesia, and the mechanism may be related to the disorder of α7nAChR mediated BDNF/TrkB-KCC2 signaling pathway. EA can alleviate postoperative hyperalgesia induced by PSD, which may be related to its effect in activating α7nAChR, inhibiting the expression of BDNF/TrkB, and up-regulating the expression of KCC2 in the spinal cord.

Paradoxical sleep deprivation and restriction promote castration-like effects and local inflammatory responses in male gerbil prostate

Paradoxical sleep deprivation and restriction promote castration-like effects and local inflammatory responses in male gerbil prostate

Effects of Paradoxical Sleep Deprivation on MCH and Hypocretin Systems

AbstractMelanin-concentrating hormone (MCH) and hypocretins (Hcrt) 1 and 2 are neuropeptides synthesized in the lateral hypothalamic area by neurons that are critical in the regulation of sleep and wakefulness. Their receptors are located in the same cerebral regions, including the frontal cortex and hippocampus. The present study aimed to assess whether 96 hours of paradoxical sleep deprivation alters the functioning of the MCH and hypocretin systems. To do this, in control rats with normal sleep (CTL) and in rats that were deprived of paradoxical sleep (SD), we quantified the following parameters: 1) levels of MCH and hypocretin-1 in the cerebrospinal fluid (CSF); 2) expression of the prepro-MCH (Pmch) and prepro-hypocretin (Hcrt) genes in the hypothalamus; 3) expression of the Mchr1 and Hcrtr1 genes in the frontal cortex and hippocampus; and 4) expression of the Hcrtr2 gene in the hippocampus. These measures were performed at 6 Zeitgeber time (ZT) points of the day (ZTs: 0, 4, 8, 12, 16, and 20). In the SD group, we found higher levels of MCH in the CSF at the beginning of the dark phase. In the frontal cortex, sleep deprivation decreased the expression of Hcrtr1 at ZT0. Moreover, we identified significant differences between the light and dark phases in the expression of Mchr1 and Hcrtr1, but only in the CTL animals. We conclude that there is a day/night modulation in the expression of components of the MCH and hypocretin systems, and this profile is affected by paradoxical sleep deprivation.

Effects of paradoxical sleep deprivation on oxidative parameters in the serum and brain of mice submitted to the animal model of hyperglycemia

The present study aimed to investigate the effects of paradoxical sleep deprivation (PSD) on behavioral and oxidative stress parameters in the brain and serum of mice submitted to the animal model of hyperglycemia induced by alloxan, mimicking the main symptom of diabetes mellitus (DM). Adults C57BL/6 male and female mice received an injection of alloxan, and ten days later, the animals were submitted to the PSD for 36 h. The animals' behavioral parameters were evaluated in the open-field test. Oxidative stress parameters [Diacetyldichlorofluorescein (DCF), Thiobarbituric acid reactive substances (TBARS), Superoxide dismutase (SOD), and Glutathione] were assessed in the frontal cortex, hippocampus, striatum, and serum. The PSD increased the male and female mice locomotion, but the alloxan's pre-administration prevented the PSD-induced hyperactivity. In addition, the male mice receiving alloxan and submitted to the PSD had elevated latency time in the first quadrant and the number of fecal boli, demonstrating increased anxiety-like behavior. The HPA-axis was hyperactivating in male and female mice pre-administered alloxan and/or PSD-submitted animals. The oxidative stress parameters were also increased in the serum of the animals administered alloxan and/or sleep-deprived mice. Despite alloxan or PSD leading to behavioral or biochemical alterations, the one did not potentiate the other in mice. However, more studies are necessary to identify the link between sleep and hyperglycemia.

Phyllanthus emblica Linn. fruit polyphenols improve acute paradoxical sleep deprivation-induced cognitive impairment and anxiety via Nrf2 pathway

Phyllanthus emblica Linn. fruit that primarily contains many polyphenols, have been considered homologous food for centuries and have been used as a remedy for a variety of ailments, including maintaining brain function. It is, however, unclear what is the mechanism of protective action of Phyllanthus emblica Linn. fruit polyphenols (PEFPs) against cognitive impairment and anxiety induced by acute paradoxical sleep deprivation (SD). Behavioral abnormalities induced by acute paradoxical SD were effectively alleviated by PEFPs, which also prevented histopathological and morphological damage to hippocampal neurons. Acute paradoxical SD-induced cognitive impairments and anxiety are treated by PEFPs through modulating a variety of biological functional modules, such as oxidative stress, inflammation/immune, cell proliferation and differentiation, metabolism, and neurotransmitter signaling. Further results showed that PEFPs markedly counteracted oxidative stress damage and neuroinflammation by activating the Nrf2 pathway. In summary, PEFPs are attractive nutraceutical ingredients for preventing cognitive impairment and anxiety associated with sleep loss.

Effect of Sleep Deprivation on the Number of Prefrontal Cortex Neuroglia Cells in Male White Rats (<i>Rattus norvegicus</i>)

Stress induced by sleep deprivation can increase inflammation and oxidative stress, destroying the pyramidal and neuroglia cells in the prefrontal cerebral cortex and interrupting cognitive and behavioral functions. This study aims to observe the difference in the number of pyramidal and neuroglia cells in the prefrontal cortex of male white rats (Rattus norvegicus) after stress induction by paradoxical sleep deprivation (PSD) and total sleep deprivation (TSD). This study was conducted in the Anatomy Laboratory of the Faculty of Medicine, Universitas Jenderal Soedirman, from November 2019 to February 2020. The method of this study was a posttest-only design with a control group approach using ten rats for each group; that was control (K.I.), PSD (KII), and TSD (K.I.). PSD and TSD groups received sleep deprivation treatment for eight days for 20 hours/day and 24 hours/day, respectively. The mean pyramidal cell number decreased in the PSD (66.67±24.55) and TSD (65.90±34.91) compared to the control (77.10±26.11) group, but no significant differences were found between all groups (p>0.05). The mean neuroglial cell number was lower in the PSD (97.78±28.17) and TSD (75.80±22.39) compared to the control (126.00±48.81). Post-hoc Bonferroni test showed a significant difference between control and TSD (p<0.05) but not between control and PSD or PSD and TSD (p>0.05). In conclusion, there was a significant difference in the number of neuroglial cells but not pyramidal cells in the prefrontal cortex of male white rats (Rattus norvegicus) after stress induction with total sleep deprivation (TSD).

Sleep Deprivation-Induced Oxidative Stress in Rat Models: A Scoping Systematic Review.

Sleep deprivation is highly prevalent in the modern world, possibly reaching epidemic proportions. While multiple theories regarding the roles of sleep exist (inactivity, energy conservation, restoration, brain plasticity and antioxidant), multiple unknowns still remain regarding the proposed antioxidant roles of sleep. The existing experimental evidence is often contradicting, with studies pointing both toward and against the presence of oxidative stress after sleep deprivation. The main goals of this review were to analyze the existing experimental data regarding the relationship between sleep deprivation and oxidative stress, to attempt to further clarify multiple aspects surrounding this relationship and to identify current knowledge gaps. Systematic searches were conducted in three major online databases for experimental studies performed on rat models with oxidative stress measurements, published between 2015 and 2022. A total of 54 studies were included in the review. Most results seem to point to changes in oxidative stress parameters after sleep deprivation, further suggesting an antioxidant role of sleep. Alterations in these parameters were observed in both paradoxical and total sleep deprivation protocols and in multiple rat strains. Furthermore, the effects of sleep deprivation seem to extend beyond the central nervous system, affecting multiple other body sites in the periphery. Sleep recovery seems to be characterized by an increased variability, with the presence of both normalizations in some parameters and long-lasting changes after sleep deprivation. Surprisingly, most studies revealed the presence of a stress response following sleep deprivation. However, the origin and the impact of the stress response during sleep deprivation remain somewhat unclear. While a definitive exclusion of the influence of the sleep deprivation protocol on the stress response is not possible, the available data seem to suggest that the observed stress response may be determined by sleep deprivation itself as opposed to the experimental conditions. Due to this fact, the observed oxidative changes could be attributed directly to sleep deprivation.

Biological rhythms are correlated with Na+, K+-ATPase and oxidative stress biomarkers: A translational study on bipolar disorder

BackgroundBipolar disorder (BD) is a chronic, severe, and multifactorial psychiatric disorder. Although biological rhythms alterations, sodium potassium pump (Na+, K+-ATPase) changes, and oxidative stress appear to play a critical role in the etiology and pathophysiology of BD, the inter-connection between them has not been described. Therefore this study evaluated the association between biological rhythms, Na+, K+-ATPase, and oxidative stress parameters in BD patients and the preclinical paradoxical sleep deprivation model (PSD). MethodsA translational study was conducted, including a case-control protocol with 36 BD and 46 healthy controls (HC). Subjects completed the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN). In addition, Erythrocyte Na+, K+-ATPase activity, and oxidative and nitrosative stress markers were assessed (4-hydroxynonenal [4-HNE], 8-isoprostane [8-ISO], thiobarbituric acid reactive substances [TBARS], carbonyl, 3-nitrotyrosine [3-nitro]). In the preclinical protocol, the same biomarkers were evaluated in the frontal cortex, hippocampus, and striatum from mice submitted to the PSD. ResultsBD patients had a significantly higher total score of BRIAN versus HCs. Additionally, individuals with BD showed decreased Na+, K+-ATPase activity and increased oxidative stress parameters compared to HC without psychiatric disorders. This difference was driven by actively depressed BD subjects. The mice submitted to the PSD also demonstrated decreased Na+, K+-ATPase activity and increased oxidative stress parameters. LimitationsBRIAN biological underpinning is less well characterized; We did not control for medication status; Sample size is limited; PSD it is not a true model of BD. ConclusionsThe present study found a significant correlation between Na+, K+-ATPase and oxidative stress with changes in biological rhythms, reinforcing the importance of these parameters to BD.

STUDI EFFEKTIVITAS NANOEMULSI PURWOCENG PADA PERBAIKAN FUNGSI REPRODUKSI TIKUS PUTIH JANTAN PASCA INDUKSI SLEEP DEPRIVATION

Paradoxical sleep deprivation (PSD) or sleep disorders can affect sexual function and potentially reduce fertility rates. The active substance of Purwoceng (Pimpinella pruatjan Molk.), namely flavonoid and tannin compounds can improve the quality of function. Drug nanoemulsion is expected to increase the therapeutic effect and reduce toxicity. This study aims to determine the effect of purwoceng nanoemulsion on serum testosterone levels, testicular volume and testicular histopathology of male Wistar rats after stress induction of paradoxical sleep deprivation for 96 hours. This research is an experimental study with a post-test only design with a control group. A total of 24 rats were divided into 6 treatment groups. Group A was given PSD, group B was given PSD and sleep recovery, group C was given PSD and purwoceng extract 25 mg/300 gBW/day, group D was given PSD and purwoceng nanoemulsion 25 mg/300 gBW/day, group E was given PSD and purwoceng nanoemulsion. 50 mg/300 gBW/day, and group F was given PSD and purwoceng nanoemulsion 75 mg/300 gBW/day. Serum testosterone levels were measured by the ELISA method, testicular volume and histopathology determined using Image J software and data were analyzed by One Way ANOVA test and followed by Post Hoc Bonferroni test. Statistical analysis showed that there were significant differences in serum testosterone levels, testicular volume and testicular histopathology (p<0.005). Administration of purwoceng nanoemulsion affects serum testosterone levels, testicular volume, and testicular histopathology after PSD induction

Degenerative changes induced by paradoxical sleep deprivation in rat sublingual glands.

The aim of this study was to evaluate whether sleep deprivation can induce degenerative changes in rat sublingual glands. For this purpose, a total of 24 males were distributed into three groups: control (n = 8), in which the animals were not subjected to any procedure; sleep deprivation (n = 8) in which the animals were submitted to sleep deprivation for 96h; recovery (n = 8), in which the animals were subjected to paradoxical sleep deprivation for 96 consecutive hours followed by 96h without intervention. Morphological changes in sublingual glands as well as the immunoexpressions of some proteins, such as Ki-67, p16, cleaved caspase-3 and BCL-2 were investigated in this setting. The results showed that paradoxical sleep deprivation induced tissue degeneration as a result of the presence of pyknosis, vacuoles and areas of salivary retention, in the experimental groups. Expression of cleaved caspase 3 and BCL-2 were increased in both sleep deprivation and recovery groups. The analysis of Ki-67 showed an increase in expression only in the recovery group, associated with a decrease in p16 levels. Sleep deprivation can induce a degenerative process in the parenchyma of sublingual gland by means of dysregulation of apoptosis associated with proliferative activity.

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

Alzheimer's disease is the most common form of dementia. One of its pathological hallmarks is Aβ accumulation, which is influenced by APOE genotype and expression, as well as by sleep homeostasis. However, conflicting mechanisms for APOE roles in Aβ 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 Aβ clearance. Paradoxical sleep deprivation for 96 h increased Aβ 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 Aβ 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 Aβ clearance, sleep deprivation might also affect the degree of participation of glia in Aβ clearance, and consequently, turnover of Aβ in the brain.

The simultaneous action of acute paradoxical sleep deprivation and hypothyroidism modulates synaptosomal ATPases and acetylcholinesterase activities in rat brain

BackgroundThyroid dysfunctions as well as sleep abnormalities are usually followed by neurological, psychiatric and/or behavioral disorders. On the other hand, changes in the brain adenosine triphosphatases (ATPases) and acetylcholinesterase (AChE) activities show significant importance in pathogenetic pathways in the evolution of numerous neuropsychiatric diseases. MethodsThis study aimed to evaluate the in vivo simultaneous effects of hypothyroidism and paradoxical sleep deprivation for 72 h on synaptosomalATPases and AChE activities of whole rat brains.In order to induce hypothyroidism, 6-n-propyl-2-thiouracil was administrated in drinking water during 21 days. The modified multiple platform method was used to induce paradoxical sleep deprivation. The AChE and ATPases activities were measured using spectrophotometric methods. ResultsHypothyroidism significantly increased the activity of Na+/K+-ATPase compared to other groups, while at the same time significantly decreased AChE activity compared to the CT and SD groups. Paradoxical sleep deprivation significantly increased AChE activity compared to other groups. The simultaneous effect of hypothyroidism and sleep deprivation reduced the activity of all three enzymes (for Na+/K+-ATPase between HT/SD and HT group p < 0.0001, SD group p < 0.001,CT group p = 0.013; for ecto-ATPases between HT/SD and HT group p = 0.0034, SD group p = 0.0001, CT group p = 0.0007; for AChE between HT/SD and HT groupp < 0.05, SD group p < 0.0001, CT group p < 0.0001). ConclusionsThe effect of simultaneous existence of hypothyroidism and paradoxical sleep deprivation reduces the activity of the Na+/K+-ATPase, ecto-ATPases, and AChE, what is different from individual effect of hypothyroidism and paradoxical sleep deprivation itself. This knowledge could help in the choice of appropriate therapy in such condition.

Total Sleep Deprivation Reduces Quality of Spermatozoa in Male Albino Rat (Rattus norvegicus)

Abstract: Sleep deprivation-induced stress decreases the quality of spermatozoa due to the increase of glucocorticoid levels through the hypothalamic-pituitary-adrenal axis. Sleep recovery (SR) restores the effect of stress due to sleep deprivation by decreasing lipid peroxides and other free radicals and increasing glutathione antioxidants. This study aims to determine the spermatozoa quality in male albino rats (Rattus norvegicus) after the stress induction by diverse sleep deprivation protocols. This study is experimental research with posttest-only control group design in 30 male albino rats divided into five groups consisting of group I for negative control (no induction of sleep deprivation), group II for paradoxical sleep deprivation (PSD), group III for total sleep deprivation (TSD), group IV for PSD followed by SR, and group V for TSD followed by SR. PSD and TSD were performed by depriving rats sleep for 20 and 24 hours/day, respectively, for five days. SR was done for the next five days after PSD or TSD. Shapiro-Wilk test was used for normality of data distribution, and Levene's test was used for variance homogeneity. Comparative hypothesis was then analyzed with One Way Analysis of Variance (ANOVA) test, and significance between groups was analyzed with Tukey's Post-Hoc test. Group III (TSD) demonstrated the lowest mean of spermatozoa count (41,53±2,29), spermatozoa morphology (13,00±2,91), spermatozoa viability (31,00±7,39), and percentage of motility rate (37±8,58%) among all groups. In conclusion, total sleep deprivation (TSD) decreases the quality of spermatozoa in male albino rats (Rattus norvegicus).

Consequences of post-weaning sleep deprivation on behaviour and oxidative stress parameters in rat plasma and brain.

Sleep is essential for health: Adequate sleep is essential for healthy development and sleep deprivation results in several consequences. Indeed, sleep deprivation early in life is associated with poor behaviour and cognition, as well as impaired mental and physical health. Preclinical studies have shown that sleep deprivation alters several physiological functions later in life such as the cardiovascular, immune and endocrine systems, resulting in altered oxidative states. Most of the preclinical literature is focused on adult animals, and little is known about oxidative alterations during development, especially in the context of sleep deprivation. Hence, we adapted a classic and well-documented model of sleep deprivation, paradoxical sleep deprivation using multiple platforms, for juvenile rats and explored central and peripheral oxidative parameters, as well as the behavioural consequences of sleep deprivation post-weaning. We showed that 96 h of paradoxical sleep deprivation induced a significant reduction in body weight, decreased sucrose preference-a behaviour suggestive of anhedonia-and increased glucose and decreased cholesterol in the plasma. In the brain, we observed a decrease in reduced glutathione levels in the medial prefrontal cortex and an increase in thiobarbituric acid reactive substance levels in the hypothalamus, indicating oxidative damage in these regions. Taken together, our findings suggest that paradoxical sleep deprivation during development induces anhedonic behaviour and promotes central and peripheral alterations in oxidative parameters.

Chinese traditional formula Kaixin San suppressed ferroptosis of hippocampal neurons and cardiomyocytes in mice with paradoxical sleep deprivation

Kaixin San (KXS) is one of the most famous traditional Chinese formulas prescribed by Sun Simiao in 652 Christian era. It is composed of Panax ginseng C.A.Mey, Polygala tenuifolia, Poria cocos and Acorus calamus var. angustatus Besser. KXS is widely used for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart. However, whether KXS benefits hippocampal neurons and myocardial cells of mice impaired by paradoxical sleep deprivation (PSD) and its mechanism remains unclear. This study was aimed to investigate the effect of KXS on hippocampal neuron and cardiac ferroptosis in rapid-eye-movement (REM) sleep deprived mice and clarify its potential mechanism. PSD was induced by a modified multi-platform method. Morris water maze (MWM) was used to detect the ability of learning and memory. Cardiac morphological changes were assessed by hematoxylin and eosin (HE) staining. Heart rate was detected by a PowerLab multichannel physiological recorder. Serum levels of atrial natriuretic peptide (ANP) and lactate dehydrogenase (LDH) were measured with biochemical kits. Transmission electron microscopy (TEM), immunofluorescent, and Western blotting analysis were used to observe the process and pathway of ferrotosis in hippocampus tissue and heart tissue of PSD mice. KXS administration improved the impaired learning and memory of PSD mice. It prevented the damage of mitochondria in the hippocampus and heart of PSD mice. KXS also alleviated the myocardial injury, such as morphological damage, abnormal heart rate, serum ANP, and serum LDH induced by PSD. Further study disclosed that KXS reversed the expressions of proteins involved in ferroptosis such as TFRC, SLC7A11/xCT, GPX-4, ACSL4, and FTH1 in hippocampus and heart tissues. KXS improved learning and memory of mice with REM sleep deprivation, which was closely associated with suppressed ferroptosis in hippocampal neurons and myocardiocytes.

Levels of Cortisol and Inflammatory Cytokines after The Induction of Various Sleep Deprivation Stress Models in Male Wistar Rats

&#x0D; &#x0D; &#x0D; Sleep deprivation (SD) can modulate the production of various cytokines, including pro-inflammatory cytokines such as IL-6, TNF-α, and IFN-γ, and anti-inflammatory cytokines such as IL-10. Paradoxical sleep deprivation (PSD) increases the risk of inflammation but can be relieved by sleep recovery (SR). This study aimed to determine the differences in levels of cortisol and inflammatory cytokines (IL-6, IL-10, TNF-α, dan IFN-γ) in male Wistar rats (Rattus norvegicus) after induction of various sleep deprivation stress models. Twenty-five of male Wistar rats were randomly divided into five groups: control, PSD (20 hours of SD/day for five days), Total Sleep Deprivation or TSD (24 hours of SD/day for five days), PSD+SR (PSD followed by SR), and TSD+SR (TSD followed by SR). The plasma cortisol levels were measured with ELISA, and inflammatory cytokine levels were measured with immunoassay and calculated with fold change. Mean cortisol levels were significantly increased in treatment groups compared to the control group (p=0.029). Multivariate analysis showed no statistically significant difference in inflammatory cytokine levels of IL-6 (p=0.658), IL-10 (p=0.065), TNF-α (p=0.399), and IFN-γ (p=0.283) in all groups. In conclusion, various sleep deprivation stress models affect cortisol levels but not inflammatory cytokine levels of IL-6, IL-10, TNF-α, and IFN-γ among male Wistar rats.&#x0D; &#x0D; &#x0D;

Quercetin ameliorates memory impairment by inhibiting abnormal microglial activation in a mouse model of paradoxical sleep deprivation

Paradoxical sleep deprivation (PSD) is prevalent in modern society, and impaired memory is one of its serious consequences. The pathogenic mechanism is still unclear, and the therapeutic strategies for PSD are limited. Here, we found that quercetin treatment ameliorated memory impairments caused by PSD in a dose-dependent manner in an animal model. Quercetin could restore the dynamic changes of the gamma band while the animals performed novel object recognition (NOR) tasks as determined by electroencephalogram analysis. Morphological analysis showed that quercetin, by targeting the hippocampal CA1 region, strikingly ameliorated the overactivation of microglia induced by PSD. Mechanistically, quercetin inhibited the toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-b (NF-κB) cascade, which is critical for abnormal microglial activation following PSD stress. Our results provided experimental evidence for the therapeutic effects of quercetin on PSD-related memory impairments by suppressing TLR4/MyD88/NF-κB signaling that mediated abnormal microglia activation in the hippocampus.

The Pituitary-Adrenal Response to Paradoxical Sleep Deprivation Is Similar to a Psychological Stressor, Whereas the Hypothalamic Response Is Unique.

Stressors of different natures induce activation of the hypothalamic-pituitary-adrenal (HPA) axis at different magnitudes. Moreover, the HPA axis response to repeated exposure is usually distinct from that elicited by a single session. Paradoxical sleep deprivation (PSD) augments ACTH and corticosterone (CORT) levels, but the nature of this stimulus is not yet defined. The purpose of the present study was to qualitatively compare the stress response of animals submitted to PSD to that of rats exposed once or four times to cold, as a physiological stress, movement restraint (RST) as a mixed stressor and predator odour (PRED) as the psychological stressor, whilst animals were submitted for 1 or 4 days to PSD and respective control groups. None of the stressors altered corticotropin releasing factor immunoreactivity in the paraventricular nucleus of the hypothalamus (PVN), median eminence (ME) or central amygdala, compared to control groups, whereas vasopressin immunoreactivity in PSD animals was decreased in the PVN and increased in the ME, indicating augmented activity of this system. ACTH levels were higher after repeated stress or prolonged PSD than after single- or 1 day-exposure and control groups, whereas the CORT response was habituated by repeated stress, but not by 4-days PSD. This dissociation resulted in changes in the CORT : ACTH ratio, with repeated cold and RST decreasing the ratio compared to single exposure, but no change was seen in PRED and PSD groups. Comparing the magnitude and pattern of pituitary-adrenal response to the different stressors, PSD-induced responses were closer to that shown by PRED-exposed rats. In contrast, the hypothalamic response of PSD-exposed rats was unique, inasmuch as this was the only stressor which increased the activity of the vasopressin system. In conclusion, we propose that the pituitary-adrenal response to PSD is similar to that induced by a psychological stressor.

Purwoceng nanosuspension repairs spatial white albino wistar strains’ spatial memory degeneration after sleep deprivation

Paradoxical Sleep Deprivation (PSD) induces oxidative stress and interferes permanent memory consolidation in hippocampus. Purwoceng (Pimpinella prutjan Molken) is herbal medicine with antioxidant effect. These effects will be more effective with nanosuspension technology. The research purposes is to find effect of PSD to rats’ spatial memory reduction and to find purwoceng nanosuspension extract effect to improve rats’ spatial memory after PSD stress induction. The research method is randomized controlled trial with posttest only with control group approach to 36 white male albino rats Wistar strain which is induced by 96 hours PSD stress model. Experiment groups is regular extract 25 mg/300g BW/day, purwoceng nanosuspension extract 25 mg/300 gBW/day, 50 mg/300 gBW/day, and 75 mg/300 gBW/day. Statistical analysis found that there is no significant effect of purwoceng extract to memory traveling time (p=0,414) and memory track length (p=0,316) between pre-PSD and post-PSD group. There is significant effect of PSD stress after purwoceng administration to memory track length and memory travelling time (p=0,005). The conclusion is that there is significant correlation between the difference of memory latency and memory traveling time of MWM test between the various purwoceng nanoemulsion dose. The 25-50 mg/300 gBW/day is effective dose of purwoceng nanoemulsion extract to repairs spatial memory degeneration after PSD stress.

Paradoxical sleep deprivation induces tissue changes in the parotid gland of rats.

This study aimed to evaluate if paradoxical sleep deprivation induces some tissue changes in the parotid gland of rats. A total of 24 male Wistar rats were distributed into the following groups, as follows: Group 1-Control (CTRL; n = 8); Group 2-Sleep deprivation (PS; n = 8): the animals were submitted to Paradoxical Sleep deprivation for 96h and Group 3-Recovery (R; n = 8): the animals were submitted to sleep loss for 96h, followed by a period of 96h without any intervention. The following parameters were evaluated: microscopic analysis, immunohistochemistry for Caspase-3, Ki-67, and COX-2 and gene expression of cytochrome C, TNF-α, and Interleukins 6, 10. The results pointed out acinar atrophy, and the presence of cytoplasmic vacuoles in the parenchyma of the experimental groups. In the same groups, there was differential expression of interleukins 6, 10 and TNF-α. Apoptosis was also increased by means of cleaved caspase 3 expression. The cellular proliferation (ki-67 expression) was increased the R group. Taken together, sleep deprivation induces tissue degeneration, inflammatory process, as well as activate apoptosis in the parotid gland of rats.