Pub Date : 2025-11-01Epub Date: 2025-08-13DOI: 10.1016/j.nbscr.2025.100134
Suil Kim , Douglas G. McMahon
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 in vivo, and blocks period after-effects on clock gene rhythms following phase resetting by the vasoactive intestinal peptide in the isolated ex vivo SCN. In addition, the DNA methyltransferase inhibitor SGI-1027 blocked period after-effects of optogenetic neuronal stimulation on ex vivo 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.
{"title":"Effects of DNA methylation inhibitors on light-induced circadian clock plasticity","authors":"Suil Kim , 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":"2025-11-01","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}
Pub Date : 2025-11-01Epub Date: 2025-06-11DOI: 10.1016/j.nbscr.2025.100132
Abrar Al Maghribi , Caitlin Ottaway , Michael Rempe , Elizabeth Medina , Kaitlyn Ford , Kristan Singletary , Lucia Peixoto
Rett syndrome (RTT) is a severe, progressive neurodevelopmental disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2). 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 Mecp2-/y male mice. At baseline, Mecp2-/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, Mecp2-/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. Mecp2-/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, Mecp2-/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.
{"title":"Loss of MeCP2 leads to sleep deficits that are time-of-day dependent and worsen with sleep deprivation","authors":"Abrar Al Maghribi , Caitlin Ottaway , Michael Rempe , Elizabeth Medina , Kaitlyn Ford , Kristan Singletary , 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<sup>-/y</sup> male mice. At baseline, <em>Mecp</em>2<sup>-/y</sup> 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<sup>-/y</sup> 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<sup>-/y</sup> 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<sup>-/y</sup> 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":"2025-11-01","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}
Pub Date : 2025-11-01Epub Date: 2025-06-03DOI: 10.1016/j.nbscr.2025.100131
Abhimanyu Thakur , Raj Kishore
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.
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.
{"title":"Neurobiology of the circadian clock and its role in cardiovascular disease: Mechanisms, biomarkers, and chronotherapy","authors":"Abhimanyu Thakur , 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":"2025-11-01","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}
Pub Date : 2025-11-01Epub Date: 2025-11-07DOI: 10.1016/j.nbscr.2025.100136
Peppi Schulz , Heiko I. Stecher , Christoph S. Herrmann
Transcranial alternating current stimulation (tACS) is a promising tool for research on oscillatory brain activity, yet both behavioral and electrophysiological outcome measures show high variability across studies. One source for this variability might be chronotype and an incidental mismatch between chronotype and the time of the measurement.
14 evening type and 14 morning type participants performed a sustained attention task — once at their chronotypically optimal and once at a non-optimal time of day. TACS was applied for 20 min at the individual alpha frequency over two electrodes located at Cz and Oz. EEG was recorded for 10 min prior to and after stimulation. Sleep timing and quality were assessed with a sleep questionnaire. While planned analyses failed to find effects of stimulation and session timing on alpha power, exploratory analyses revealed that below average sleep quality in evening types in the morning was associated with no changes or unexpected decreases in alpha power after stimulation. Effects of sleep quality were present in the morning for evening types, but neither in the evening session nor in morning types. It is suggested that this effect of sleep quality reflects increased sleepiness, which could impede expected aftereffects of tACS. It is likely that effects of sleepiness might be especially relevant when people are stimulated at a chronotypically non-optimal time. Due to the exploratory nature of these sleep effects and their presence in only a small subgroup leading to low power and confidence, future systematic sham-controlled studies are needed to clarify the relationship between sleep, time of day and chronotype in -tACS proposed here.
{"title":"Chronotype in alpha-tACS: Preliminary evidence hints at sleep quality modulation of aftereffects in evening types in the morning","authors":"Peppi Schulz , Heiko I. Stecher , Christoph S. Herrmann","doi":"10.1016/j.nbscr.2025.100136","DOIUrl":"10.1016/j.nbscr.2025.100136","url":null,"abstract":"<div><div>Transcranial alternating current stimulation (tACS) is a promising tool for research on oscillatory brain activity, yet both behavioral and electrophysiological outcome measures show high variability across studies. One source for this variability might be chronotype and an incidental mismatch between chronotype and the time of the measurement.</div><div>14 evening type and 14 morning type participants performed a sustained attention task — once at their chronotypically optimal and once at a non-optimal time of day. TACS was applied for 20 min at the individual alpha frequency over two electrodes located at Cz and Oz. EEG was recorded for 10 min prior to and after stimulation. Sleep timing and quality were assessed with a sleep questionnaire. While planned analyses failed to find effects of stimulation and session timing on alpha power, exploratory analyses revealed that below average sleep quality in evening types in the morning was associated with no changes or unexpected decreases in alpha power after stimulation. Effects of sleep quality were present in the morning for evening types, but neither in the evening session nor in morning types. It is suggested that this effect of sleep quality reflects increased sleepiness, which could impede expected aftereffects of tACS. It is likely that effects of sleepiness might be especially relevant when people are stimulated at a chronotypically non-optimal time. Due to the exploratory nature of these sleep effects and their presence in only a small subgroup leading to low power and confidence, future systematic sham-controlled studies are needed to clarify the relationship between sleep, time of day and chronotype in <span><math><mi>α</mi></math></span>-tACS proposed here.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"19 ","pages":"Article 100136"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518970","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}
Pub Date : 2025-05-01Epub Date: 2025-04-15DOI: 10.1016/j.nbscr.2025.100118
Mark R. Opp , Luca Imeri
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.
{"title":"Sleep and immune health: How dogs, goats and ‘factor S’ shaped a field","authors":"Mark R. Opp , 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}
Pub Date : 2025-05-01Epub Date: 2025-05-20DOI: 10.1016/j.nbscr.2025.100129
Amber R. Li , Bhaavyaa Shah , Michael L. Thomas , Michael J. McCarthy , Alejandro D. Meruelo
Background
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.
Methods
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.
Results
All four sleep disorder groups showed significantly higher odds of autoimmune diagnosis relative to regular sleepers (p < 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.
Conclusions
Distinct sleep phenotypes were associated with autoimmune conditions. These associations may reflect shared or bidirectional links between sleep disruption and immune dysregulation.
背景：睡眠和昼夜节律紊乱与免疫失调的联系越来越紧密，但在人群水平上与自身免疫性疾病的关联仍未得到充分探讨。我们研究了延迟睡眠阶段障碍（DSPD）、阻塞性睡眠呼吸暂停（OSA）、原发性失眠和嗜睡是否与自身免疫性疾病有关。方法数据来自All of Us Research Program注册Tier Dataset v8。根据临床诊断，参与者被分为睡眠障碍组，正常睡眠者作为对照组。自身免疫性疾病的定义使用snomed编码记录。采用罕见病logistic回归分析DSPD与原发性失眠症；采用1:5倾向评分匹配法对OSA和嗜睡症进行分析。调整后的logistic回归模型包括年龄、出生性别、种族、民族、收入、BMI和慢性炎症诊断。e值评估了对未测量混杂的稳健性。结果4个睡眠障碍组的自身免疫诊断率均高于正常睡眠组(p <；2.2 × 10−16)。调整后的优势比为：DSPD (OR = 0.26；95% ci: 0.15-0.45), osa (or = 0.46；95% CI: 0.41-0.52)，原发性失眠(OR = 0.46；95% CI: 0.41-0.52)和嗜睡症(OR = 0.48；95% ci: 0.46-0.50)。年龄较大、女性和慢性炎症与较高的自身免疫性患病率相关。亚洲人种和BMI与自身免疫风险呈负相关；高收入出乎意料地与更高的自身免疫诊断相关。结论不同的睡眠表型与自身免疫性疾病相关。这些关联可能反映了睡眠中断和免疫失调之间的共享或双向联系。
{"title":"Sleep and circadian disorders as risk factors for autoimmune disease: A population-based study","authors":"Amber R. Li , Bhaavyaa Shah , Michael L. Thomas , Michael J. McCarthy , 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 < 2.2 × 10<sup>−16</sup>). 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}
Pub Date : 2025-05-01Epub Date: 2024-12-25DOI: 10.1016/j.nbscr.2024.100110
Erika Satomi , Daniel Apolinário , Regina Miksian Magaldi , Alexandre Leopold Busse , Gisele Cristina Vieira Gomes , Elyse Ribeiro , Pedro Rodrigues Genta , Ronaldo Delmonte Piovezan , Dalva Poyares , Wilson Jacob-Filho , Claudia Kimie Suemoto
Background
Although sleep duration and sleep-related breathing disorders were associated with dementia previously, few studies examined the association between circadian rhythm association and cognitive status.
Objective
We aimed to investigate the association of rest and activity rhythm with cognitive performance in older people with cognitive complaints and less education.
Methods
Activity rhythm was evaluated with wrist actigraphy in 109 community-dwelling older people with cognitive complaints without diagnosed dementia. Each participant completed a neuropsychological battery and was classified as having cognitive impairment (MCI), dementia, or normal cognition. We used adjusted multinomial logistic regression and linear regression models to compare sleep and circadian non-parametric measures with cognitive groups and cognitive z-scores, respectively.
Results
The mean age of the 109 participants was 79.3 ± 6.3 years old, 74% were women, 68% were white, and the mean education was 5.6 ± 5.2 years. Daytime activity intensity was associated with better language (β = 0.178; 95% CI = 0.022, 0.334; p = 0.03) and visuospatial performance (β = 0.158; 95%CI = 0.008, 0.308; p = 0.04). Also, less fragmented rhythm was associated with better visuospatial (β = 0.172; 95%CI = 0.025, 0.320; p = 0.02) and global cognitive scores (β = 0.134; 95%CI = 0.005, 0.263; p = 0.04). More interdaily stability was associated with a lower risk of MCI and dementia (RR = 0.54; 95%CI = 0.29–0.99; p = 0.04, and RR = 0.44; 95%CI = 0.21–0.94; p = 0.03, respectively). Moreover, more daytime activity (RR = 0.40; 95%CI = 0.18–0.89; p = 0.02) and less rhythm fragmentation (RR = 0.31; 95%CI = 0.14–0.73; p = 0.007) were associated with lower risk for dementia.
Conclusion
Daytime activity intensity and fragmented rhythm during the day and night may play an important role as markers for cognitive impairment in less educated populations. Future studies with larger samples should confirm these findings.
{"title":"Beyond sleep: Rest and activity rhythm as a marker of preclinical and mild dementia in older adults with less education","authors":"Erika Satomi , Daniel Apolinário , Regina Miksian Magaldi , Alexandre Leopold Busse , Gisele Cristina Vieira Gomes , Elyse Ribeiro , Pedro Rodrigues Genta , Ronaldo Delmonte Piovezan , Dalva Poyares , Wilson Jacob-Filho , Claudia Kimie Suemoto","doi":"10.1016/j.nbscr.2024.100110","DOIUrl":"10.1016/j.nbscr.2024.100110","url":null,"abstract":"<div><h3>Background</h3><div>Although sleep duration and sleep-related breathing disorders were associated with dementia previously, few studies examined the association between circadian rhythm association and cognitive status.</div></div><div><h3>Objective</h3><div>We aimed to investigate the association of rest and activity rhythm with cognitive performance in older people with cognitive complaints and less education.</div></div><div><h3>Methods</h3><div>Activity rhythm was evaluated with wrist actigraphy in 109 community-dwelling older people with cognitive complaints without diagnosed dementia. Each participant completed a neuropsychological battery and was classified as having cognitive impairment (MCI), dementia, or normal cognition. We used adjusted multinomial logistic regression and linear regression models to compare sleep and circadian non-parametric measures with cognitive groups and cognitive z-scores, respectively.</div></div><div><h3>Results</h3><div>The mean age of the 109 participants was 79.3 ± 6.3 years old, 74% were women, 68% were white, and the mean education was 5.6 ± 5.2 years. Daytime activity intensity was associated with better language (β = 0.178; 95% CI = 0.022, 0.334; p = 0.03) and visuospatial performance (β = 0.158; 95%CI = 0.008, 0.308; p = 0.04). Also, less fragmented rhythm was associated with better visuospatial (β = 0.172; 95%CI = 0.025, 0.320; p = 0.02) and global cognitive scores (β = 0.134; 95%CI = 0.005, 0.263; p = 0.04). More interdaily stability was associated with a lower risk of MCI and dementia (RR = 0.54; 95%CI = 0.29–0.99; p = 0.04, and RR = 0.44; 95%CI = 0.21–0.94; p = 0.03, respectively). Moreover, more daytime activity (RR = 0.40; 95%CI = 0.18–0.89; p = 0.02) and less rhythm fragmentation (RR = 0.31; 95%CI = 0.14–0.73; p = 0.007) were associated with lower risk for dementia.</div></div><div><h3>Conclusion</h3><div>Daytime activity intensity and fragmented rhythm during the day and night may play an important role as markers for cognitive impairment in less educated populations. Future studies with larger samples should confirm these findings.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"18 ","pages":"Article 100110"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To better understand the relationship between the rest-activity rhythms and cognitive impairments during aging, we assessed the longitudinal changes in the rest-activity rhythms in an elderly population and their possible detrimental effect on the hippocampal network.
This was done longitudinally in a rural cohort with two actigraphic assessments and brain imaging examinations, seven years apart. A segmentation of the hippocampus and its related structures was used to assess volumes and functional connectivity in this network based on anatomical and resting state functional data. Regression models were carried out to investigate the potential association of the evolution of sleep and rest-activity rhythms parameters with the structural and functional integrity of the hippocampal network.
Our sample was composed of 33 subjects aged 75.2 ± 2.4 years old at the first time point with 40% of women. After seven years, the sleep of our participants did not change but their rest-activity rhythms did (p < 0.05), with a decrease in relative amplitude (∂RA = −0.021) and stability (∂IS = −0.044) as well as an increase in fragmentation (∂IV = +0.072). The deterioration of rest-activity rhythms was correlated with a lower anterior hippocampal volume (p corrected <0.05) while no correlation with functional connectivity was observed.
These findings suggest that a degradation of rest-activity rhythms in people over 70 years old could constitute a factor of hippocampal vulnerability. Preventive interventions should consider rest-activity rhythms in the oldest-old population.
{"title":"Age-related disturbances in rest-activity rhythms and integrity of the hippocampal network: An exploratory study","authors":"Aurore Jouvencel , Bixente Dilharreguy , Marion Baillet , Karine Pérès , Jean-François Dartigues , Hélène Amieva , Willy Mayo , Gwenaëlle Catheline","doi":"10.1016/j.nbscr.2024.100111","DOIUrl":"10.1016/j.nbscr.2024.100111","url":null,"abstract":"<div><div>To better understand the relationship between the rest-activity rhythms and cognitive impairments during aging, we assessed the longitudinal changes in the rest-activity rhythms in an elderly population and their possible detrimental effect on the hippocampal network.</div><div>This was done longitudinally in a rural cohort with two actigraphic assessments and brain imaging examinations, seven years apart. A segmentation of the hippocampus and its related structures was used to assess volumes and functional connectivity in this network based on anatomical and resting state functional data. Regression models were carried out to investigate the potential association of the evolution of sleep and rest-activity rhythms parameters with the structural and functional integrity of the hippocampal network.</div><div>Our sample was composed of 33 subjects aged 75.2 ± 2.4 years old at the first time point with 40% of women. After seven years, the sleep of our participants did not change but their rest-activity rhythms did (p < 0.05), with a decrease in relative amplitude (∂RA = −0.021) and stability (∂IS = −0.044) as well as an increase in fragmentation (∂IV = +0.072). The deterioration of rest-activity rhythms was correlated with a lower anterior hippocampal volume (p corrected <0.05) while no correlation with functional connectivity was observed.</div><div>These findings suggest that a degradation of rest-activity rhythms in people over 70 years old could constitute a factor of hippocampal vulnerability. Preventive interventions should consider rest-activity rhythms in the oldest-old population.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"18 ","pages":"Article 100111"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-01Epub Date: 2025-04-28DOI: 10.1016/j.nbscr.2025.100124
Charlene Y.P. Guerrero, Madelyn R. Cusick, Amanda J. Samaras, Natalie S. Shamon, Daniel J. Cavanaugh
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 Drosophila 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.
{"title":"The cell-intrinsic circadian clock is dispensable for lateral posterior clock neuron regulation of Drosophila rest-activity rhythms","authors":"Charlene Y.P. Guerrero, Madelyn R. Cusick, Amanda J. Samaras, Natalie S. Shamon, 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}
Pub Date : 2025-05-01Epub Date: 2025-02-13DOI: 10.1016/j.nbscr.2025.100114
William A. Banks
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.
{"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}
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