Neurobiology of Sleep and Circadian Rhythms最新文献

{"title":"Identification of photoperiod as a regulator of dopamine-mediated behavior in female mice","authors":"Beimnet B. Kassaye ,&nbsp;Alexis N. Jameson ,&nbsp;Katherine Moore ,&nbsp;Douglas G. McMahon ,&nbsp;Brad A. Grueter","doi":"10.1016/j.nbscr.2025.100135","DOIUrl":"10.1016/j.nbscr.2025.100135","url":null,"abstract":"<div><div>Photoperiod is the primary environmental cue that regulates changes in behavior across seasons. Previously, we have shown that photoperiod has sex-specific effects on synaptic dopamine dynamics in the nucleus accumbens (NAc). Further, evidence suggests that the dopamine transporter (DAT) is a potential locus of action for the sex-specific effects of photoperiod on NAc dopamine. The NAc is a critical node within the reward circuit that brings motivation to action, and changes to NAc dopamine dynamics at the synapse can result in robust changes in behaviors. Cocaine is a psychostimulant that targets monoamine transporters, including DAT, and generates robust behavioral effects. Thus, using cocaine-mediated behavior, we can determine whether photoperiod impacts DAT function and dopamine physiology. Here, using male and female mice we examined the effect of seasonally relevant photoperiods on DAT function in the NAc and dopamine-dependent behavior. We found that females raised in Short, winter-like photoperiod have blunted cocaine-induced hyperlocomotion. Conversely, females raised in Long, summer-like photoperiod exhibit greater DA release and cocaine-mediated DAT inhibition while we observe decreased sensitivity to cocaine-associated learning. The combined work presented here provides evidence that photoperiod has differential, female-specific effects on NAc DAT function and DAT-mediated behaviors.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"19 ","pages":"Article 100135"},"PeriodicalIF":0.0,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of DNA methylation inhibitors on light-induced circadian clock plasticity","authors":"Suil Kim ,&nbsp;Douglas G. McMahon","doi":"10.1016/j.nbscr.2025.100134","DOIUrl":"10.1016/j.nbscr.2025.100134","url":null,"abstract":"<div><div>The suprachiasmatic nucleus (SCN) of the hypothalamus is a principal light-responsive circadian clock that adjusts circadian rhythms in mammalian physiology and behavior to changes in external light signals. Although mechanisms underlying how light acutely resets the timing of circadian rhythms have been characterized, it remains elusive how light signals induce lasting changes in circadian period, known as period after-effects. Here we have found that the period after-effects on circadian behavior of changing photoperiods are blocked by application of the DNA methyltransferase inhibitor RG108 near the SCN. At the level of single light pulses acting as clock-resetting stimulations, RG108 significantly attenuates period after-effects following acute phase shifts in behavioral rhythms <em>in vivo</em>, and blocks period after-effects on clock gene rhythms following phase resetting by the vasoactive intestinal peptide in the isolated <em>ex vivo</em> SCN. In addition, the DNA methyltransferase inhibitor SGI-1027 blocked period after-effects of optogenetic neuronal stimulation on <em>ex vivo</em> SCN rhythms. Acute clock resetting shifts themselves, however, do not appear to require DNA methylation at the SCN and behavioral levels, in contrast to subsequent period plasticity. Our results demonstrate that DNA methylation inhibitors block light-induced period after-effects in response to photoperiods and single light pulses. Together with previous studies showing that DNA methylation in the SCN is essential for period after-effects of non-24hr light cycles (T-cycles), this suggests that DNA methylation in the SCN may be a widespread mechanism of light-induced circadian period plasticity.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"19 ","pages":"Article 100134"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep regularity and duration are associated with depression severity in a nationally representative United States sample","authors":"Katherine A. Maki,&nbsp;Li Yang,&nbsp;Nicole Farmer,&nbsp;Shreya Papneja,&nbsp;Gwenyth R. Wallen,&nbsp;Jennifer J. Barb","doi":"10.1016/j.nbscr.2025.100133","DOIUrl":"10.1016/j.nbscr.2025.100133","url":null,"abstract":"<div><h3>Background</h3><div>Sleep hygiene is integral to health, and sleep regularity may be associated with mental health outcomes in addition to duration. Although sleep and depression relationships are well-studied, the relative impact of different sleep factors remains unclear. As patient-specific factors and health behaviors influence sleep and mental health, we investigated associations between sleep and depression severity considering such factors in a United States sample of adults.</div></div><div><h3>Methods</h3><div>Two cycles (2011–2012, 2013–2014) from the National Health and Nutritional Examination Survey were studied. Objective sleep duration (day and night), and the sleep regularity index (SRI) were calculated from physical activity monitors worn for seven days. Complex survey procedures with four-year weights were used, and backward selection was used to test relevant variables in the fully adjusted regression model.</div></div><div><h3>Results</h3><div>Among participants (n = 7297), we found associations between sleep-associated variables and SRI, with increased daytime sleep being the strongest correlate of decreased SRI. In the fully adjusted model, lower SRI scores and reduced subjective night sleep remained significantly associated with depression. Sex was an additional independent predictor, with females exhibiting higher depression scores, and a significant sex × SRI interaction revealed that the inverse relationship between SRI and depressive symptoms was stronger in females than in males. Health behaviors, including active tobacco and cannabis use, were also associated with increased depression severity in the adjusted model.</div></div><div><h3>Conclusions</h3><div>Daytime sleep may serve as an SRI proxy, although additional cohorts should confirm relationships. Higher depression severity was associated with different sleep components, emphasizing the importance of sleep hygiene in mental health. Behaviors like current smoking and cannabis use were also associated with increased depression. Research exploring the temporality and interactions between these factors may assist in non-pharmacologic depression treatment.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"19 ","pages":"Article 100133"},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of MeCP2 leads to sleep deficits that are time-of-day dependent and worsen with sleep deprivation","authors":"Abrar Al Maghribi ,&nbsp;Caitlin Ottaway ,&nbsp;Michael Rempe ,&nbsp;Elizabeth Medina ,&nbsp;Kaitlyn Ford ,&nbsp;Kristan Singletary ,&nbsp;Lucia Peixoto","doi":"10.1016/j.nbscr.2025.100132","DOIUrl":"10.1016/j.nbscr.2025.100132","url":null,"abstract":"<div><div>Rett syndrome (RTT) is a severe, progressive neurodevelopmental disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (<em>MECP2</em>). Sleep problems are frequently reported in Rett Syndrome, but the exact nature remains relatively unexplored. Currently there is limited understanding of MECP2's role in sleep architecture and regulation. In this study, we employed longitudinal electroencephalographic (EEG) and electromyographic (EMG) recordings to investigate sleep architecture during baseline conditions as well as the homeostatic response to sleep deprivation (SD) in <em>Mecp</em>2^-/y male mice. At baseline, <em>Mecp</em>2^-/y mice have more non-rapid-eye-movement (NREM) sleep and less rapid-eye-movement (REM) sleep than their wildtype littermates during the light period. However, <em>Mecp</em>2^-/y mice display altered sleep timing during the dark period, spending more time in both NREM and REM during the first half and less time during the second half. <em>Mecp</em>2^-/y mice also have lower EEG spectral power during wake and NREM at higher frequencies and higher power at lower frequencies during REM in compared to wildtype mice. In response to SD, <em>Mecp</em>2^-/y mice can accumulate and discharge sleep pressure normally and show a sleep rebound. However, baseline differences in sleep architecture are heightened after SD. Overall, our findings show that RTT mice exhibit distinct sleep patterns compared to wildtype mice, with time-of-day-dependent variations in NREM and REM sleep, as well as altered EEG spectral properties, that become more pronounced following SD. Future research should explore the molecular mechanisms through which MECP2 regulates sleep architecture to develop targeted therapeutics for sleep disturbances in RTT patients.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"19 ","pages":"Article 100132"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurobiology of the circadian clock and its role in cardiovascular disease: Mechanisms, biomarkers, and chronotherapy","authors":"Abhimanyu Thakur ,&nbsp;Raj Kishore","doi":"10.1016/j.nbscr.2025.100131","DOIUrl":"10.1016/j.nbscr.2025.100131","url":null,"abstract":"<div><div>Cardiovascular diseases are paramount cause of morbidity in aging population and aging disrupts normal circadian rhythm cycle. Circadian rhythms, regulated by the suprachiasmatic nucleus in the brain, profoundly influence cardiovascular health through intricate neurobiological mechanisms. These rhythms regulate gene expression in cardiomyocytes, modulate autonomic nervous system (ANS) activity, and synchronize cardiovascular functions with environmental cues, ultimately impacting heart rate, blood pressure, and susceptibility to cardiac events. The intricate relationship between circadian rhythms and cardiovascular health emphasizes the critical role of brain-heart communication in physiological processes.</div><div>This review explores the neurobiology of circadian clock in cardiovascular disease, exploring how peripheral clocks in cardiovascular tissues influence organ physiology and how their disruption contributes to pathogenesis. The examination of neurobiological pathways linking circadian clock to cardiovascular disease, including ANS function, neuroendocrine signaling, and inflammatory responses, highlights the interplay between brain and heart. By probing environmental and lifestyle factors that modulate the circadian clock, as well as sex-specific variations in circadian rhythms, the review provides a comprehensive understanding of how these factors impact cardiovascular health. The discussion of emerging concepts, such as exosome-mediated intracellular communication in circadian physiology, offers new insights into the molecular mechanisms underlying brain-heart interactions. Furthermore, the exploration of diagnostic potential and therapeutic strategies, particularly chronotherapy, emphasizes the importance of targeting the circadian clock for disease prevention and treatment in cardiovascular medicine. This comprehensive assessment not only advances our understanding about circadian clock's role in cardiovascular health but also paves the way for innovative approaches in theranostic, ultimately improving patient outcomes.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"19 ","pages":"Article 100131"},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep and immune health: How dogs, goats and ‘factor S’ shaped a field","authors":"Mark R. Opp ,&nbsp;Luca Imeri","doi":"10.1016/j.nbscr.2025.100118","DOIUrl":"10.1016/j.nbscr.2025.100118","url":null,"abstract":"<div><div>Chronic insufficient sleep kills! Although this statement has high ‘face validity’, it is only recently that empirical evidence existed to support it. There are now sufficient data for numerous meta-analyses and systematic reviews to demonstrate that chronic insufficient sleep is associated with many inflammatory pathologies that are a public health burden. As a result, it is now well accepted that sleep is important for physical and mental health. This awareness derives from research that began in the late 19th and early 20th centuries and continues to the present day. In this narrative review we trace this rich history within the context of the research contributions of Professor James Krueger and his colleagues. The historic and current research by Professor Krueger and colleagues is fundamental to the many ongoing pre-clinical and clinical research programs focused on all aspects of sleep and immune health.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"18 ","pages":"Article 100118"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep and circadian disorders as risk factors for autoimmune disease: A population-based study","authors":"Amber R. Li ,&nbsp;Bhaavyaa Shah ,&nbsp;Michael L. Thomas ,&nbsp;Michael J. McCarthy ,&nbsp;Alejandro D. Meruelo","doi":"10.1016/j.nbscr.2025.100129","DOIUrl":"10.1016/j.nbscr.2025.100129","url":null,"abstract":"<div><h3>Background</h3><div>Sleep and circadian disruption have been increasingly linked to immune dysregulation, yet population-level associations with autoimmune disease remain underexplored. We examined whether delayed sleep phase disorder (DSPD), obstructive sleep apnea (OSA), primary insomnia, and hypersomnia were associated with autoimmune conditions in a large, diverse U.S. cohort.</div></div><div><h3>Methods</h3><div>Data were drawn from the All of Us Research Program Registered Tier Dataset v8. Participants were categorized into sleep disorder groups based on clinical diagnoses, with regular sleepers serving as controls. Autoimmune disease was defined using SNOMED-coded records. DSPD and primary insomnia were analyzed using rare disease logistic regression; OSA and hypersomnia were analyzed using 1:5 propensity score matching. Adjusted logistic regression models included age, sex at birth, race, ethnicity, income, BMI, and chronic inflammatory diagnosis. E-values assessed robustness to unmeasured confounding.</div></div><div><h3>Results</h3><div>All four sleep disorder groups showed significantly higher odds of autoimmune diagnosis relative to regular sleepers (p &lt; 2.2 × 10⁻¹⁶). Adjusted odds ratios were: DSPD (OR = 0.26; 95 % CI: 0.15–0.45), OSA (OR = 0.46; 95 % CI: 0.41–0.52), primary insomnia (OR = 0.46; 95 % CI: 0.41–0.52), and hypersomnia (OR = 0.48; 95 % CI: 0.46–0.50). Older age, female sex, and chronic inflammation were associated with higher autoimmune prevalence. Asian race and BMI were inversely associated with autoimmune risk; higher income was unexpectedly associated with greater autoimmune diagnosis.</div></div><div><h3>Conclusions</h3><div>Distinct sleep phenotypes were associated with autoimmune conditions. These associations may reflect shared or bidirectional links between sleep disruption and immune dysregulation.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"18 ","pages":"Article 100129"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cell-intrinsic circadian clock is dispensable for lateral posterior clock neuron regulation of Drosophila rest-activity rhythms","authors":"Charlene Y.P. Guerrero,&nbsp;Madelyn R. Cusick,&nbsp;Amanda J. Samaras,&nbsp;Natalie S. Shamon,&nbsp;Daniel J. Cavanaugh","doi":"10.1016/j.nbscr.2025.100124","DOIUrl":"10.1016/j.nbscr.2025.100124","url":null,"abstract":"<div><div>Circadian control of behavior arises from intercommunication among a distributed network of circadian clock neurons in the brain. Single-cell sequencing and brain connectome data support the division of the ∼240 brain clock neurons in <em>Drosophila</em> into ∼20 subclusters, and functional studies demonstrate that these populations differentially contribute to behavioral outputs. Here, we have used genetic tools that enable highly selective, cell-specific manipulations to investigate the role of molecular clock function and neuronal activity within the lateral posterior clock neurons (LPNs) in the regulation of rest-activity rhythms. We find that genetic silencing of these neurons, which compromises signaling with downstream neuronal targets, substantially reduces the strength of free-running rest-activity rhythms. In contrast, locomotor activity patterns are robust to CRISPR-mediated disruption of molecular clock cycling within the LPNs. We conclude that the LPNs act as driven oscillators that retain the capacity to transmit circadian information in the absence of cell-intrinsic molecular clocks.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"18 ","pages":"Article 100124"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergies from a distance: Inspirations from the struggles of Dr James M Krueger","authors":"William A. Banks","doi":"10.1016/j.nbscr.2025.100114","DOIUrl":"10.1016/j.nbscr.2025.100114","url":null,"abstract":"<div><div>In this article for Dr Krueger's Festschrift, I trace how his early career influenced many aspects in the fields of sleep, neuroimmunology, and the microbiome. Mostly, however, I trace how his career and interests intertwined with those of Abba J. Kastin and mine and how he exerted a profound influence on the direction of our studies. Dr. Krueger, while developing his career as a sleep researcher, encountered resistance to his work that required two major paradigm shifts: 1) that bacterial products could affect sleep and 2) that small peptides can cross the blood-brain barrier (BBB) in sufficient amounts to affect brain functioning. Dr Kastin had also shown that small peptides administered peripherally could affect brain function and postulated that this was because they could cross the BBB. Our efforts to determine whether peptides could or could not cross the BBB were bolstered by Dr Krueger's exemplary struggles.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"18 ","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immune mechanisms of infection: what we know and potential conserved mechanisms affecting sleep during infection","authors":"Mark R. Zielinski ,&nbsp;Sean D. Carey ,&nbsp;John A. Craig","doi":"10.1016/j.nbscr.2025.100121","DOIUrl":"10.1016/j.nbscr.2025.100121","url":null,"abstract":"<div><div>Evidence indicates relationships between sleep and the innate immune system during homeostatic sleep and sleep responses after infection. The innate immune system and sleep-like states are highly conserved between simple species and more complex species such as humans. A wide variety of bacteria, viruses, and parasites change sleep patterns in the host during infection. The effects of infection on sleep can occur, in part, due to the bolus and route of infection, prior exposure, immune status of the individual/organism, and the type of pathogen. In addition, elements of circadian patterns and sleep prior to and after infection can modulate the infection pathology and resolution. Innate immune molecules, such as the cytokines interleukin-1 beta and tumor necrosis factor-alpha, fluctuate with the time of day of increased activity and sleep propensity, increase in response to increased waking activity from sleep loss, and are altered from infection by bacteria and viruses to alter sleep and the electroencephalogram. This review focuses innate immune mechanisms of how pathogen recognition receptors, pathogen-associated molecular patterns and danger-associated molecular patterns, energy-related molecules, oxidative stress, and inflammasomes are activated with infection to potentially affect sleep.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"18 ","pages":"Article 100121"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}