Melatonin improves maternal sleep deprivation-induced learning and memory impairment, inflammation, and synaptic dysfunction in murine male adult offspring.

INTRODUCTION: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown. METHODS: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting. RESULTS: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. CONCLUSIONS: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.

Accelerometer-measured physical activity and sedentary behaviour are associated with C-reactive protein in US adults who get insufficient sleep: A threshold and isotemporal substitution effect analysis.

This study aimed to investigate the association between physical activity, sedentary behaviour and chronic inflammation in short sleep adults. The study included 2,113 NHANES participants with self-reported insufficient sleep. C-reactive protein (CRP) was used as the inflammatory biomarker. Physical activity and sedentary behaviour were objectively measured by accelerometers. Weighted regression model, two - piecewise linear regression model, and restricted cubic splines were applied to evaluate associations mentioned above. An isotemporal substitution model was used to assess the modelled effects of replacing sedentary time (ST) with moderate-to-vigorous levels of physical activity (MVPA) or light physical activity (LPA). After adjusting for potential confounding factors, higher levels of ST and lower levels of LPA or MVPA were associated with higher CRP levels. Isotemporal substitution analysis indicated that replacing 30 minutes of ST with 30 minutes of MVPA was associated with a significant decrease in CRP levels. Saturation analysis suggested that the association between MVPA and CRP may plateau at over 20 minutes of MVPA per day. Findings of this study provides insight into the potential benefits of replacing ST with MVPA. This study also suggests that increasing MVPA beyond a certain point may not provide additional anti-inflammatory benefits in a short sleep population.

Calibrated to drive: Measuring self-assessed driving ability and perceived workload after prolonged sitting and sleep restriction.

Self-assessed driving ability may differ from actual driving performance, leading to poor calibration (i.e., differences between self-assessed driving ability and actual performance), increased risk of accidents and unsafe driving behaviour. Factors such as sleep restriction and sedentary behaviour can impact driver workload, which influences driver calibration. This study aims to investigate how sleep restriction and prolonged sitting impact driver workload and driver calibration to identify strategies that can lead to safer and better calibrated drivers. Participants (n = 84, mean age = 23.5 ± 4.8, 49 % female) undertook a 7-day laboratory study and were randomly allocated to a condition: sitting 9-h sleep opportunity (Sit9), breaking up sitting 9-h sleep opportunity (Break9), sitting 5-h sleep opportunity (Sit5) and breaking up sitting 5-h sleep opportunity (Break5). Break9 and Break5 conditions completed 3-min of light-intensity walking on a treadmill every 30 min between 09:00-17:00 h, while participants in Sit9 and Sit5 conditions remained seated. Each participant completed a 20-min simulated commute in the morning and afternoon each day and completed subjective assessments of driving ability and perceived workload before and after each commute. Objective driving performance was assessed using a driving simulator measuring speed and lane performance metrics. Driver calibration was analysed using a single component and 3-component Brier Score. Correlational matrices were conducted as an exploratory analysis to understand the strength and direction of the relationship between subjective and objective driving outcomes. Analyses revealed participants in Sit9 and Break9 were significantly better calibrated for lane variability, lane position and safe zone-lane parameters at both time points (p < 0.0001) compared to Sit5 and Break5. Break5 participants were better calibrated for safe zone-speed and combined safe zone parameters (p < 0.0001) and speed variability at both time points (p = 0.005) compared to all other conditions. Analyses revealed lower perceived workload scores at both time points for Sit9 and Break9 participants compared to Sit5 and Break5 (p = <0.001). Breaking up sitting during the day may reduce calibration errors compared to sitting during the day for speed keeping parameters. Future studies should investigate if different physical activity frequency and intensity can reduce calibration errors, and better align a driver's self-assessment with their actual performance.

Insufficient Sleep and Behavioral Health in the Military: A 5-Country Perspective.

PURPOSE OF REVIEW: The goal of this paper was to highlight the degree to which sleep, behavioral health, and leader involvement were interrelated using data from militaries in five English-speaking countries: Australia, Canada, New Zealand, the UK, and the United States. RECENT FINDINGS: Many service members reported sleeping fewer than the recommended 7 h/night: 34.9%, 67.2%, and 77.2% of respondents from New Zealand, Canada, and the United States, respectively. Countries reporting shorter sleep duration also reported fewer insomnia-related difficulties, likely reflecting higher sleep pressure from chronic sleep loss. Across all countries, sleep problems were positively correlated with behavioral health symptoms. Importantly, leader promotion of healthy sleep was positively correlated with more sleep and negatively correlated with sleep problems and behavioral health symptoms. Insufficient sleep in the military is ubiquitous, with serious implications for the behavioral health and functioning of service members. Leaders should attend to these risks and examine ways to promote healthy sleep in service members.

Sleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes.

Sleep disorders increase the risk and mortality of heart disease, but the brain-heart interaction has not yet been fully elucidated. Cuproptosis is a copper-dependent type of cell death activated by the excessive accumulation of intracellular copper. Here, we showed that 16 weeks of sleep fragmentation (SF) resulted in elevated copper levels in the male mouse heart and exacerbated myocardial ischemia-reperfusion injury with increased myocardial cuproptosis and apoptosis. Mechanistically, we found that SF promotes sympathetic overactivity, increases the germination of myocardial sympathetic nerve terminals, and increases the level of norepinephrine in cardiac tissue, thereby inhibits VPS35 expression and leads to impaired ATP7A related copper transport and copper overload in cardiomyocytes. Copper overload further leads to exacerbated cuproptosis and apoptosis, and these effects can be rescued by excision of the sympathetic nerve or administration of copper chelating agent. Our study elucidates one of the molecular mechanisms by which sleep disorders aggravate myocardial injury and suggests possible targets for intervention.

Effects of sleep deprivation on food-related Pavlovian-instrumental transfer: a randomized crossover experiment.

Recent research suggests that insufficient sleep elevates the risk of obesity. Although the mechanisms underlying the relationship between insufficient sleep and obesity are not fully understood, preliminary evidence suggests that insufficient sleep may intensify habitual control of behavior, leading to greater cue-elicited food-seeking behavior that is insensitive to satiation. The present study tested this hypothesis using a within-individual, randomized, crossover experiment. Ninety-six adults underwent a one-night normal sleep duration (NSD) condition and a one-night total sleep deprivation (TSD) condition. They also completed the Pavlovian-instrumental transfer paradigm in which their instrumental responses for food in the presence and absence of conditioned cues were recorded. The sleep × cue × satiation interaction was significant, indicating that the enhancing effect of conditioned cues on food-seeking responses significantly differed across sleep × satiation conditions. However, this effect was observed in NSD but not TSD, and it disappeared after satiation. This finding contradicted the hypothesis but aligned with previous literature on the effect of sleep disruption on appetitive conditioning in animals-sleep disruption following learning impaired the expression of appetitive behavior. The present finding is the first evidence for the role of sleep in Pavlovian-instrumental transfer effects. Future research is needed to further disentangle how sleep influences motivational mechanisms underlying eating.

Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia.

BACKGROUND: Sleep loss is a common public health problem that causes hyperalgesia, especially that after surgery, which reduces the quality of life seriously. METHODS: The 48-h sleep restriction (SR) mouse model was created using restriction chambers. In vivo imaging, transmission electron microscopy (TEM), immunofluorescence staining and Western blot were performed to detect the status of the blood-spinal cord barrier (BSCB). Paw withdrawal mechanical threshold (PWMT) was measured to track mouse pain behavior. The role of infiltrating regulatory T cells (Tregs) and endothelial cells (ECs) in mouse glycolysis and BSCB damage were analyzed using flow cytometry, Western blot, CCK-8 assay, colorimetric method and lactate administration. RESULTS: The 48-h SR made mice in sleep disruption status and caused an acute damage to the BSCB, resulting in hyperalgesia and neuroinflammation in the spinal cord. In SR mice, the levels of glycolysis and glycolysis enzymes of ECs in the BSCB were found significantly decreased [CON group vs. SR group: CD31+Glut1+ cells: p < 0.001], which could cause dysfunction of ECs and this was confirmed in vitro. Increased numbers of infiltrating T cells [p < 0.0001] and Treg population [p < 0.05] were detected in the mouse spinal cord after 48-h SR. In the co-cultured system of ECs and Tregs in vitro, the competition of Tregs for glucose resulted in the glycolysis disorder of ECs [Glut1: p < 0.01, ENO1: p < 0.05, LDHα: p < 0.05; complete tubular structures formed: p < 0.0001; CCK8 assay: p < 0.001 on 24h, p < 0.0001 on 48h; glycolysis level: p < 0.0001]. An administration of sodium lactate partially rescued the function of ECs and relieved SR-induced hyperalgesia. Furthermore, the mTOR signaling pathway was excessively activated in ECs after SR in vivo and those under the inhibition of glycolysis or co-cultured with Tregs in vitro. CONCLUSIONS: Affected by glycolysis disorders of ECs due to glucose competition with infiltrating Tregs through regulating the mTOR signaling pathway, hyperalgesia induced by 48-h SR is attributed to neuroinflammation and damages to the barriers, which can be relieved by lactate supplementation.

The Effect of Sleep Deprivation on Brain Fingerprint Stability: A Magnetoencephalography Validation Study.

This study examined the stability of the functional connectome (FC) over time using fingerprint analysis in healthy subjects. Additionally, it investigated how a specific stressor, namely sleep deprivation, affects individuals' differentiation. To this aim, 23 healthy young adults underwent magnetoencephalography (MEG) recording at three equally spaced time points within 24 h: 9 a.m., 9 p.m., and 9 a.m. of the following day after a night of sleep deprivation. The findings indicate that the differentiation was stable from morning to evening in all frequency bands, except in the delta band. However, after a night of sleep deprivation, the stability of the FCs was reduced. Consistent with this observation, the reduced differentiation following sleep deprivation was found to be negatively correlated with the effort perceived by participants in completing the cognitive task during sleep deprivation. This correlation suggests that individuals with less stable connectomes following sleep deprivation experienced greater difficulty in performing cognitive tasks, reflecting increased effort.

Neuroligin-2 shapes individual slow waves during slow-wave sleep and the response to sleep deprivation in mice.

BACKGROUND: Sleep disturbances are a common comorbidity to most neurodevelopmental disorders and tend to worsen disease symptomatology. It is thus crucial to understand mechanisms underlying sleep disturbances to improve patients' quality of life. Neuroligin-2 (NLGN2) is a synaptic adhesion protein regulating GABAergic transmission. It has been linked to autism spectrum disorders and schizophrenia in humans, and deregulations of its expression were shown to cause epileptic-like hypersynchronized cerebral activity in rodents. Importantly, the absence of Nlgn2 (knockout: KO) was previously shown to alter sleep-wake duration and quality in mice, notably increasing slow-wave sleep (SWS) delta activity (1-4 Hz) and altering its 24-h dynamics. This type of brain oscillation is involved in memory consolidation, and is also a marker of homeostatic sleep pressure. Sleep deprivation (SD) is notably known to impair cognition and the physiological response to sleep loss involves GABAergic transmission. METHODS: Using electrocorticographic (ECoG) recordings, we here first aimed to verify how individual slow wave (SW; 0.5-4 Hz) density and properties (e.g., amplitude, slope, frequency) contribute to the higher SWS delta activity and altered 24-h dynamics observed in Nlgn2 KO mice. We further investigated the response of these animals to SD. Finally, we tested whether sleep loss affects the gene expression of Nlgn2 and related GABAergic transcripts in the cerebral cortex of wild-type mice using RNA sequencing. RESULTS: Our results show that Nlgn2 KO mice have both greater SW amplitude and density, and that SW density is the main property contributing to the altered 24-h dynamics. We also found the absence of Nlgn2 to accelerate paradoxical sleep recovery following SD, together with profound alterations in ECoG activity across vigilance states. Sleep loss, however, did not modify the 24-h distribution of the hypersynchronized ECoG events observed in these mice. Finally, RNA sequencing confirmed an overall decrease in cortical expression of Nlgn2 and related GABAergic transcripts following SD in wild-type mice. CONCLUSIONS: This work brings further insight into potential mechanisms of sleep duration and quality deregulation in neurodevelopmental disorders, notably involving NLGN2 and GABAergic neurotransmission.

Years of life lost due to insufficient sleep and associated economic burden in China from 2010-18.

Background: Research on the health and economic costs due to insufficient sleep remains scant in developing countries. In this study we aimed to estimate the years of life lost (YLLs) due to short sleep and quantify its economic burden in China. Methods: We estimated both individual and aggregate YLLs due to short sleep (ie, ≤6 hours) among Chinese adults aged 20 years or older by sex and five-year age groups in 2010, 2014, and 2018. YLL estimates were derived from 1) the prevalence of short sleep using three survey waves of the China Family Panel Studies, 2) relative mortality risks from meta-analyses, and 3) life tables in China. YLL was the difference between the estimated life expectancy of an individual in the short sleep category vs in the recommended sleep category. We estimated the economic cost using the human capital approach. Results: The sample sizes of the three survey waves were 31 393, 31 207, and 28 618. Younger age groups and men had more YLLs due to short sleep compared to their counterparts. For individuals aged 20-24, men had an average YLL of nearly 0.95, in contrast to the approximate 0.75 in women across the observed years of 2010, 2014, and 2018. The trend in individual YLLs remained consistent over these years. In aggregate, China experienced a rise from 66.75 million YLLs in 2010 to 95.29 million YLLs in 2014, and to 115.05 million YLLs in 2018. Compared to 2010 (USD 191.83 billion), the associated economic cost in 2014 increased to USD 422.24 billion, and the cost in 2018 more than tripled (USD 628.15 billion). The percentage of cost to Chinese gross domestic product in corresponding years was 3.23, 4.09, and 4.62%. Conclusions: Insufficient sleep is associated with substantial YLLs in China, potentially impacting the population's overall life expectancy. The escalating economic toll attributed to short sleep underscores the urgent need for public health interventions to improve sleep health at the population level.

Sleep rebound leads to marked recovery of prolonged sleep deprivation-induced adversities in the stress response and hippocampal neuroplasticity of male rats.

BACKGROUND: Sleep disturbances are not only frequent symptoms, but also risk factors for major depressive disorder. We previously reported that depressed patients who experienced "Hypersomnia" showed a higher and more rapid response rate under paroxetine treatment, but the underlying mechanism remains unclear. The present study was conducted to clarify the beneficial effects of sleep rebound through an experimental "Hypersomnia" rat model on glucocorticoid and hippocampal neuroplasticity associated with antidepressive potency. METHODS: Thirty-four male Sprague-Dawley rats were subjected to sham treatment, 72-h sleep deprivation, or sleep deprivation and subsequent follow-up for one week. Approximately half of the animals were sacrificed to evaluate adrenal weight, plasma corticosterone level, hippocampal content of mRNA isoforms, and protein of the brain-derived neurotrophic factor (Bdnf) gene. In the other half of the rats, Ki-67- and doublecortin (DCX)-positive cells in the hippocampus were counted via immunostaining to quantify adult neurogenesis. RESULTS: Prolonged sleep deprivation led to adrenal hypertrophy and an increase in the plasma corticosterone level, which had returned to normal after one week follow-up. Of note, sleep deprivation-induced decreases in hippocampal Bdnf transcripts containing exons II, IV, VI, and IX and BDNF protein levels, Ki-67-(+)-proliferating cells, and DCX-(+)-newly-born neurons were not merely reversed, but overshot their normal levels with sleep rebound. LIMITATIONS: The present study did not record electroencephalogram or assess behavioral changes of the sleep-deprived rats. CONCLUSIONS: The present study demonstrated that prolonged sleep deprivation-induced adversities are reversed or recovered by sleep rebound, which supports "Hypersomnia" in depressed patients as having a beneficial pharmacological effect.

Association between sleep quality and dry eye disease: a literature review and meta-analysis.

OBJECTIVE: The purpose of this article is to systematically review the association between dry eye and sleep quality. METHODS: PubMed, EMBASE, Cochrane, Web of Science, and grey literature databases were searched for observational studies published before April 2023. Meta-analysis was performed using STAT15 software. RESULTS: A total of 21 studies with 419,218 participants were included. The results showed that the dry eye subjects had a worse sleep quality than the healthy population, with poorer subjective sleep quality, longer sleep latency, and a higher risk of unhealthy sleep duration such as insufficient sleep or excessive sleep. The Pittsburgh Sleep Quality Index (PSQI) scores of the dry eye subjects were significantly higher than those of the control subjects (WMD = 1.78, 95%CI: 1.06, 2.50, P < 0.001). The dry eye subjects scored higher than the control subjects in sleep quality, sleep latency, and sleep disturbance in PSQI; there was no difference between the dry eye individuals and control subjects in sleep duration, sleep efficiency, daytime dysfunction, and sleep medication scores. The risk of sleep disorders in the dry eye subjects was significantly higher than that in the non-dry eye subjects (RR = 2.20, 95%CI: 1.78, 2.72, P < 0.001); the risk of insufficient sleep in the dry eye subjects was higher than that in the control subjects (RR = 3.76, 95%CI: 3.15, 4.48, P < 0.001), and the prevalence of excessive sleepiness in dry eye subjects was higher than that in the control subjects (RR = 5.53, 95%CI: 3.83, 7.18, P < 0.001). The ESS scores of the dry eye subjects were significantly higher than those of the control subjects (WMD = 3.02, 95%CI: 2.43, 3.60, P < 0.01). CONCLUSION: Our meta-analysis suggests that individuals with dry eye have a worse sleep quality than the healthy population, with poorer subjective sleep quality, longer sleep latency, and higher risk of unhealthy sleep duration such as insufficient sleep or excessive sleepiness.

A resting-state EEG dataset for sleep deprivation.

To investigate the impact of sleep deprivation (SD) on mood, alertness, and resting-state electroencephalogram (EEG), we present an eyes-open resting-state EEG dataset. The dataset comprises EEG recordings and cognitive data from 71 participants undergoing two testing sessions: one involving SD and the other normal sleep. In each session, participants engaged in eyes-open resting-state EEG. The Psychomotor Vigilance Task (PVT) was employed for alertness measurement. Emotional and sleepiness were measured using Positive and Negative Affect Scale (PANAS) and Stanford Sleepiness Scale (SSS). Additionally, to examine the influence of individual sleep quality and traits on SD, Pittsburgh Sleep Quality Index (PSQI) and Buss-Perry Aggression Questionnaire (BPAQ) were utilized. This dataset's sharing may contribute to open EEG measurements in the field of SD.

Differentially expressed genes of esophageal tissue in male acute and chronic sleep deprivation mice.

Gastroesophageal reflux disease (GERD) is associated with sleep disturbances. However, mechanisms underlying these interactions remain unclear. Male acute and chronic sleep deprivation (SD) mice were used for this study. Mice in the chronic SD group exhibited anxiety- and depression-like behaviors. We further performed high-throughput genome sequencing and bioinformatics analysis to screen for featured differentially expressed genes (DEGs) in the esophageal tissue. The acute SD group, comprised 25 DEGs including 14 downregulated and 11 upregulated genes. Compared with the acute SD group, more DEGs were present in the chronic SD group, with a total of 169 DEGs, including 88 downregulated and 81 upregulated genes. Some DEGs that were closely related to GERD and associated esophageal diseases were significantly different in the chronic SD group. Quantitative real-time polymerase chain reaction verified the downregulation of Krt4, Krt13, Krt15 and Calml3 and upregulation of Baxl1 and Per3. Notably, these DEGs are involved in biological processes, which might be the pathways of the neuroregulatory mechanisms of DEGs expression.

[Glymphatic dysfunction and sleep disorders: indirect effects on Alzheimer's disease]. / Glimfaticheskaya disfunktsiya i narusheniya sna: oposredovannoe vliyanie na bolezn' Al'tsgeimera.

Modern research raises the question of the potentially significant role of glymphatic dysfunction in the development of neurodegeneration and pathological aging. The exact molecular mechanisms are not yet fully understood, but there is ample evidence of a link between sleep deprivation and decreased clearance of ß-amyloid and other neurotoxin proteins that are associated with the development of neurodegenerative diseases, particularly Alzheimer's disease. The review analyzes current scientific information in this area of research, describes the latest scientific discoveries of the features of the glymphatic system, and also illustrates studies of markers that presumably indicate a deterioration in the glymphatic system. The relationship between sleep deprivation and pathophysiological mechanisms associated with neurodegenerative diseases is considered, and potential targets that can be used to treat or delay the development of these disorders are noted.

Faecalibacterium prausnitzii Supplementation Prevents Intestinal Barrier Injury and Gut Microflora Dysbiosis Induced by Sleep Deprivation.

Sleep deprivation (SD) leads to impaired intestinal barrier function and intestinal flora disorder, especially a reduction in the abundance of the next generation of probiotic Faecalibacterium prausnitzii (F. prausnitzii). However, it remains largely unclear whether F. prausnitzii can ameliorate SD-induced intestinal barrier damage. A 72 h SD mouse model was used in this research, with or without the addition of F. prausnitzii. The findings indicated that pre-colonization with F. prausnitzii could protect against tissue damage from SD, enhance goblet cell count and MUC2 levels in the colon, boost tight-junction protein expression, decrease macrophage infiltration, suppress pro-inflammatory cytokine expression, and reduce apoptosis. We found that the presence of F. prausnitzii helped to balance the gut microbiota in SD mice by reducing harmful bacteria like Klebsiella and Staphylococcus, while increasing beneficial bacteria such as Akkermansia. Ion chromatography analysis revealed that F. prausnitzii pretreatment increased the fecal butyrate level in SD mice. Overall, these results suggested that incorporating F. prausnitzii could help reduce gut damage caused by SD, potentially by enhancing the intestinal barrier and balancing gut microflora. This provides a foundation for utilizing probiotics to protect against intestinal illnesses.

Mitochondrial antioxidant elamipretide improves learning and memory impairment induced by chronic sleep deprivation in mice.

BACKGROUND: The inflammation and synaptic dysfunction induced by mitochondrial dysfunction play essential roles in the learning and memory impairment associated with sleep dysfunction. Elamipretide (SS-31), a novel mitochondrion-targeted antioxidant, was proven to improve mitochondrial dysfunction, the inflammatory response, synaptic dysfunction, and cognitive impairment in models of cerebral ischemia, sepsis, and type 2 diabetes. However, the potential for SS-31 to improve the cognitive impairment induced by chronic sleep deprivation (CSD) and its underlying mechanisms is unknown. METHODS: Adult c57BL/6J mice were subjected to CSD for 21 days using an activity wheel accompanied by daily intraperitoneal injection of SS-31 (5 mg/kg). The novel object recognition and Morris water maze test were used to evaluate hippocampus-dependent cognitive function. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine the effects of CSD and SS-31 on markers of mitochondria, inflammation response, and synaptic function. Enzyme-linked immunosorbent assays were used to examine the levels of proinflammatory cytokines. RESULTS: SS-31 could improve the cognitive impairment induced by CSD. In particular, SS-31 treatment restored the CSD-induced decrease in sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator alpha levels and the increase in levels nuclear factor kappa-B and inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha. Furthermore, SS-31 significantly increased the levels of brain-derived neurotrophic factor, postsynaptic density protein-95, and synaptophysin in CSD mice. CONCLUSION: Taken together, these results suggest that SS-31 could improve CSD-induced mitochondrial biogenesis dysfunction, inflammatory response, synaptic dysfunction, and cognitive impairment by increasing SIRT1 expression levels.

Crocin (bioactive compound of Crocus sativus L.) potently restores REM sleep deprivation-induced manic- and obsessive-compulsive-like behaviors in female rats.

Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors including hyperlocomotion. On the other hand, crocin (one of the main compounds of Crocus sativus L. or Saffron) may be beneficial in the improvement of mental and cognitive dysfunctions. Also, crocin can restore the deleterious effects of SD on mental and cognitive processes. In this study, we investigated the effect of REM SD on female rats' behaviors including depression- and anxiety-like behaviors, locomotion, pain perception, and obsessive-compulsive-like behavior, and also, the potential effect of crocin on REM SD effects. We used female rats because evidence on the role of REM SD in modulating psychological and behavioral functions of female (but not male) rats is limited. REM SD was induced for 14 days (6h/day), and crocin (25, 50, and 75 mg/kg) was injected intraperitoneally. Open field test, forced swim test, hot plate test, and marble burying test were used to assess rats' behaviors. The results showed REM SD-induced manic-like behavior (hyperlocomotion). Also, REM SD rats showed decreased anxiety- and depression-like behavior, pain subthreshold (the duration it takes for the rat to feel pain), and showed obsessive compulsive-like behavior. However, crocin at all doses partially or fully reversed REM SD-induced behavioral changes. In conclusion, our results suggested the possible comorbidity of OCD and REM SD-induced manic-like behavior in female rats or the potential role of REM SD in the etiology of OCD, although more studies are needed. In contrast, crocin can be a possible therapeutic choice for decreasing manic-like behaviors.

How BDNF affects working memory in acute sleep deprivation: The mediating role of spontaneous brain activity.

The brain-derived neurotrophic factor (BDNF) mediates the plasticity associated with memory processing, and compensatorily increases after acute sleep deprivation (SD). However, whether the altered spontaneous brain activity mediates the association between BDNF and working memory in SD remains unknown. Here, we aimed to probe the mediating role of the spontaneous brain activity between plasma BDNF and WM function in SD. A total of 30 healthy subjects with regular sleep were enrolled in this study. Resting-sate functional magnetic resonance imaging (fMRI) scans and the peripheral blood were collected before and after 24 h SD. All participants also received n-back task assessing working memory (WM) performance. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were calculated to reflect the intensity of regional spontaneous brain activity. Plasma BDNF was measured by sandwich ELISA. Our results revealed a significant decline in WM and increase in plasma BDNF level after SD, and negative association between the changed WM performance and plasma BDNF level. Specially, the ALFF of the left inferior parietal cortex and right inferior frontal cortex, and fALFF of the left anterior cingulate and medial prefrontal cortex and left posterior opercular cortex regulated the association between the BDNF and one-back reaction time respectively. Our results suggest that the association between BDNF and working memory may be mediated through regional spontaneous brain activity involving in the cerebral cortex, which may provide new sight into the interaction between neurotrophic factors and cognition, and potential targets for noninvasive brain stimulation on WM decline after acute SD.