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Liu YF, Cong W, Zhou CM, Yu Y, Zhang XJ. Relationship between inflammatory factors, lactic acid levels, acute skin failure, bad mood, and sleep quality. World J Psychiatry 2025; 15:102763. [DOI: 10.5498/wjp.v15.i4.102763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/26/2024] [Accepted: 02/08/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND The central link between septic shock and acute skin failure (ASF) is the inflammatory response, which occurs throughout disease progression and can lead to systemic inflammatory response syndrome. Patients often experience bad moods, sleep disorders, and other health issues. Despite recognizing these factors, no studies have examined the correlation between inflammatory factors, lactic acid levels, ASF, mood disturbances, and sleep quality in critically ill patients. We hypothesize that higher levels of inflammatory factors and lactic acid are associated with more severe ASF and poorer mood and sleep quality, which may inform clinical treatment for septic shock and ASF.
AIM To explore the relationship between inflammatory factors, lactic acid levels, the severity of ASF, bad mood, and sleep quality.
METHODS The retrospective study included 150 patients with septic shock from the Second Hospital of Dalian Medical University, categorized into ASF (n = 35) or non-ASF groups (n = 115). We compared the peripheral blood inflammatory factors, including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), lactic acid levels, skin mottling score (SMS), modified early warning score (MEWS), self-rating depression scale (SDS), self-rating anxiety scale (SAS), and Pittsburgh sleep quality index (PSQI) scores. Pearson correlation analysis assessed relationships among these variables.
RESULTS The ASF group had significantly higher levels of CRP (19.60 ± 4.10 vs 15.30 ± 2.96 mg/mL), IL-6 (298.65 ± 48.65 vs 268.66 ± 33.66 pg/L), procalcitonin, lactic acid (8.42 ± 2.32 vs 5.70 ± 1.27 mmol/L), SMS [0 (0, 1) vs 3 (2, 3)], MEWS (9.34 ± 1.92 vs 6.48 ± 1.96), SAS (61.63 ± 12.03 vs 53.71 ± 12.48), SDS (60.17 ± 12.64 vs 52.27 ± 12.64), and PSQI scores (14.23 ± 3.94 vs 8.69 ± 2.46) compared with the non-ASF group (all P < 0.001). Pearson correlation analysis revealed that IL-6, CRP, TNF-α, and lactic acid were positively correlated with SMS, MEWS, SAS, SDS, and PSQI scores (P < 0.05).
CONCLUSION Peripheral blood levels of IL-6, CRP, TNF-α, and lactic acid correlate positively with SMS, MEWS, SAS, SDS, and PSQI in critically ill patients with ASF.
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Affiliation(s)
- Yu-Fei Liu
- Department of Emergency Critical Care Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, Liaoning Province, China
| | - Wen Cong
- Department of Psychiatry, Dalian Seventh People’s Hospital (Dalian Mental Health Center), Dalian 116023, Liaoning Province, China
| | - Chang-Ming Zhou
- Department of Emergency Critical Care Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, Liaoning Province, China
| | - Yang Yu
- Department of Intensive Care Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, Liaoning Province, China
| | - Xin-Jie Zhang
- Department of Intensive Care Medicine, The Second Hospital of Dalian Medical University, Dalian 116027, Liaoning Province, China
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Saputro RE, Chou CC, Lin YY, Tarumi T, Liao YH. Exercise-mediated modulation of autonomic nervous system and inflammatory response in sleep-deprived individuals: A narrative reviews of implications for cardiovascular health. Auton Neurosci 2025; 259:103256. [PMID: 40073691 DOI: 10.1016/j.autneu.2025.103256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 01/25/2025] [Accepted: 02/28/2025] [Indexed: 03/14/2025]
Abstract
Sleep deprivation is a growing concern in cardiovascular risk, causing physiological disruptions like autonomic dysregulation and inflammation. Recent research indicates that sleep deprivation increases sympathetic nervous activity while decreasing parasympathetic activity, leading to increased blood pressure, impaired endothelial function, and heightened inflammation. Exercise has emerged as a non-pharmacological approach to increase cardiovascular health. However, the impact of exercise on sleep deprivation-induced changes in autonomic activity and inflammation remains unclear. To explore this, we reviewed studies investigating the effects of acute exercise on autonomic regulation and inflammatory markers following sleep deprivation. We conducted a narrative review of the literature. PubMed/MEDLINE, Google Scholar, and Web of Science (WOS) searched the articles between May 2022 and April 2023. The papers had to: [1] focus on recent studies between 2000 and 2023; [2] consist of sleep deprivation participants; [3] be published in English. Acute moderate- to high-intensity exercise after sleep deprivation may reduce parasympathetic activity, trigger pro-inflammatory cytokines, and delay recovery to normal levels. In contrast, regular exercise routines may mitigate the adverse effects of sleep deprivation on autonomic regulation and reduce systemic inflammation. Sleep deprivation can lead to autonomic imbalance, increased blood pressure, and increased inflammatory responses, which are further amplified by acute exercise, increasing the cardiovascular burden. When sleep deprivation occurs, exercise intensity and timing should be carefully chosen to avoid adverse cardiovascular health risks.
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Affiliation(s)
- Riki Edo Saputro
- Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan; Department of Physical Education, Universitas Wahid Hasyim, Semarang 50224, Indonesia
| | - Chun-Chung Chou
- Physical Education Office, National Taipei University of Technology, Taipei 10608, Taiwan
| | - Yi-Yuan Lin
- Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan.
| | - Takashi Tarumi
- Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology, Higashi, Tsukuba, Ibaraki 305-8566, Japan
| | - Yi-Hung Liao
- Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan.
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Hong S, Lee DB, Yoon DW, Yoo SL, Kim J. The Effect of Sleep Disruption on Cardiometabolic Health. Life (Basel) 2025; 15:60. [PMID: 39860000 PMCID: PMC11766988 DOI: 10.3390/life15010060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/03/2025] [Accepted: 01/04/2025] [Indexed: 01/27/2025] Open
Abstract
Sleep disruption has emerged as a significant public health concern with profound implications for metabolic health. This review synthesizes current evidence demonstrating the intricate relationships between sleep disturbances and cardiometabolic dysfunction. Epidemiological studies have consistently demonstrated that insufficient sleep duration (<7 h) and poor sleep quality are associated with increased risks of obesity, type 2 diabetes, and cardiovascular disease. The underlying mechanisms are multifaceted, involving the disruption of circadian clock genes, alterations in glucose and lipid metabolism, the activation of inflammatory pathways, and the modulation of the gut microbiome. Sleep loss affects key metabolic regulators, including AMPK signaling and disrupts the secretion of metabolic hormones such as leptin and ghrelin. The latest evidence points to the role of sleep-induced changes in the composition and function of gut microbiota, which may contribute to metabolic dysfunction through modifications in the intestinal barrier and inflammatory responses. The NLRP3 inflammasome and NF-κB signaling pathways have been identified as crucial mediators linking sleep disruption to metabolic inflammation. An understanding of these mechanisms has significant implications for public health and clinical practice, suggesting that improving sleep quality could be an effective strategy for preventing and treating cardiometabolic disorders in modern society.
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Affiliation(s)
- SeokHyun Hong
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.); (D.-B.L.); (S.-L.Y.)
- Department of Biomedical Laboratory Science, College of Health Science, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea
| | - Da-Been Lee
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.); (D.-B.L.); (S.-L.Y.)
| | - Dae-Wui Yoon
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.); (D.-B.L.); (S.-L.Y.)
- Department of Biomedical Laboratory Science, College of Health Science, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea
| | - Seung-Lim Yoo
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.); (D.-B.L.); (S.-L.Y.)
- Department of Biomedical Laboratory Science, College of Health Science, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea
| | - Jinkwan Kim
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.); (D.-B.L.); (S.-L.Y.)
- Department of Biomedical Laboratory Science, College of Health Science, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea
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Coluk Y, Peker EGG, Yildirmak S, Keskin A, Yildirim G. Exploring the protective role of green tea extract against cardiovascular alterations induced by chronic REM sleep deprivation via modulation of inflammation and oxidative stress. BMC Complement Med Ther 2024; 24:351. [PMID: 39363261 PMCID: PMC11448275 DOI: 10.1186/s12906-024-04643-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 09/12/2024] [Indexed: 10/05/2024] Open
Abstract
BACKGROUND Chronic Rapid eye movement (REM) sleep deprivation has been associated with various cardiovascular alterations, including disruptions in antioxidant defense mechanisms, lipid metabolism, and inflammatory responses. This study investigates the therapeutic potential of green tea extract (GTE) in mitigating these adverse effects. METHODS A total of 24 male Wistar albino rats were used in this study and divided into the control group (n = 8), Chronic-REM Sleep Deprivation (CRSD) Group (n = 8) and Chronic-REM SD + Green Tea 200 (CRSD + GTE200) Group (n = 8). After 21 days, a comprehensive analysis of paraoxonase (PON1), arylesterase (ARE), malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), proinflammatory cytokines, and lipid profiles in aortic tissue, heart tissue, and serum was conducted in a sleep-deprived rat model. RESULTS Chronic REM sleep deprivation led to a significant reduction in PON1 and ARE levels in aortic (p = 0.046, p = 0.035 respectively) and heart tissues (p = 0.020, p = 0.019 respectively), indicative of compromised antioxidant defenses. MDA levels increased, and NOx levels decreased, suggesting oxidative stress and impaired vascular function. Lipid profile alterations, including increased triglycerides and total cholesterol, were observed in serum. Elevated levels of inflammatory cytokines (IL-6 and TNF-alpha) further indicated an inflammatory response (p = 0.007, p = 0.018 respectively). GTE administration demonstrated a protective role, restoring antioxidant enzyme levels, suppressing lipid peroxidation, and improving NOx levels. CONCLUSION These findings suggest the therapeutic potential of GTE in alleviating the cardiovascular impairments of chronic REM sleep deprivation, emphasizing its candidacy for further clinical exploration as a natural intervention in sleep-related disorders and associated cardiovascular risks.
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Affiliation(s)
- Yonca Coluk
- Department of Otorhinolaryngology, Faculty of Medicine, Giresun University, Giresun, 28200, Turkey.
| | - Emine Gulceri Gulec Peker
- Department of Natural and Mathematical Sciences, Faculty of Engineering, Giresun University, Giresun, 28200, Turkey
| | - Sembol Yildirmak
- Department of Biochemistry, Faculty of Medicine, Mersin University, Mersin, 33010, Turkey
| | - Arif Keskin
- Department of Anatomy, Faculty of Medicine, Giresun University, Giresun, 28200, Turkey
| | - Guven Yildirim
- Private Practice, Otorhinolaryngology, İstanbul, 34360, Turkey
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Engert LC, Ledderose C, Biniamin C, Birriel P, Buraks O, Chatterton B, Dang R, Daniel S, Eske A, Reed T, Tang A, Bertisch SM, Mullington JM, Junger WG, Haack M. Effects of low-dose acetylsalicylic acid on the inflammatory response to experimental sleep restriction in healthy humans. Brain Behav Immun 2024; 121:142-154. [PMID: 39043348 PMCID: PMC11389483 DOI: 10.1016/j.bbi.2024.07.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 07/01/2024] [Accepted: 07/20/2024] [Indexed: 07/25/2024] Open
Abstract
BACKGROUND Sleep deficiencies, such as manifested in short sleep duration or insomnia symptoms, are known to increase the risk for multiple disease conditions involving immunopathology. Inflammation is hypothesized to be a mechanism through which deficient sleep acts as a risk factor for these conditions. Thus, one potential way to mitigate negative health consequences associated with deficient sleep is to target inflammation. Few interventional sleep studies investigated whether improving sleep affects inflammatory processes, but results suggest that complementary approaches may be necessary to target inflammation associated with sleep deficiencies. We investigated whether targeting inflammation through low-dose acetylsalicylic acid (ASA, i.e., aspirin) is able to blunt the inflammatory response to experimental sleep restriction. METHODS 46 healthy participants (19F/27M, age range 19-63 years) were studied in a double-blind randomized placebo-controlled crossover trial with three protocols each consisting of a 14-day at-home monitoring phase followed by an 11-day (10-night) in-laboratory stay (sleep restriction/ASA, sleep restriction/placebo, control sleep/placebo). In the sleep restriction/ASA condition, participants took low-dose ASA (81 mg/day) daily in the evening (22:00) during the at-home phase and the subsequent in-laboratory stay. In the sleep restriction/placebo and control sleep/placebo conditions, participants took placebo daily. Each in-laboratory stay started with 2 nights with a sleep opportunity of 8 h/night (23:00-07:00) for adaptation and baseline measurements. Under the two sleep restriction conditions, participants were exposed to 5 nights of sleep restricted to a sleep opportunity of 4 h/night (03:00-07:00) followed by 3 nights of recovery sleep with a sleep opportunity of 8 h/night. Under the control sleep condition, participants had a sleep opportunity of 8 h/night throughout the in-laboratory stay. During each in-laboratory stay, participants had 3 days of intensive monitoring (at baseline, 5th day of sleep restriction/control sleep, and 2nd day of recovery sleep). Variables, including pro-inflammatory immune cell function, C-reactive protein (CRP), and actigraphy-estimated measures of sleep, were analyzed using generalized linear mixed models. RESULTS Low-dose ASA administration reduced the interleukin (IL)-6 expression in LPS-stimulated monocytes (p<0.05 for condition*day) and reduced serum CRP levels (p<0.01 for condition) after 5 nights of sleep restriction compared to placebo administration in the sleep restriction condition. Low-dose ASA also reduced the amount of cyclooxygenase (COX)-1/COX-2 double positive cells among LPS-stimulated monocytes after 2 nights of recovery sleep following 5 nights of sleep restriction compared to placebo (p<0.05 for condition). Low-dose ASA further decreased wake after sleep onset (WASO) and increased sleep efficiency (SE) during the first 2 nights of recovery sleep (p<0.001 for condition and condition*day). Baseline comparisons revealed no differences between conditions for all of the investigated variables (p>0.05 for condition). CONCLUSION This study shows that inflammatory responses to sleep restriction can be reduced by preemptive administration of low-dose ASA. This finding may open new therapeutic approaches to prevent or control inflammation and its consequences in those experiencing sleep deficiencies. TRIAL REGISTRATION ClinicalTrials.gov NCT03377543.
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Affiliation(s)
- Larissa C Engert
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA
| | - Carola Ledderose
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Surgery, University of California San Diego, San Diego, CA, USA
| | - Careen Biniamin
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Paola Birriel
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Olivia Buraks
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Bryan Chatterton
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Rammy Dang
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Surya Daniel
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Annika Eske
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Taylor Reed
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Ava Tang
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Suzanne M Bertisch
- Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Janet M Mullington
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA
| | - Wolfgang G Junger
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Surgery, University of California San Diego, San Diego, CA, USA
| | - Monika Haack
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
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Liu S, Ma X, Chen Y, Zhao Y, Luo R, Wu Z, Li Y, Qian Y, Wang W, Dong S, Zhou Z, Li S, Xiao Y, Zhu X, Tian Y, Guo J. Multiplex influences on vigilance and biochemical variables induced by sleep deprivation. Front Sports Act Living 2024; 6:1412044. [PMID: 39005627 PMCID: PMC11239445 DOI: 10.3389/fspor.2024.1412044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 06/11/2024] [Indexed: 07/16/2024] Open
Abstract
Introduction Sleep loss and sleep deprivation (SD) cause deleterious influences on health, cognition, mood and behaviour. Nevertheless, insufficient sleep and SD are prevalent across many industries and occur in various emergencies. The deleterious consequences of SD have yet to be fully elucidated. This study aimed to assess the extensive influences of SD on physiology, vigilance, and plasma biochemical variables. Methods Seventeen volunteers were recruited to participate in a 32.5-h SD experiment. Multiple physiological and cognitive variables, including tympanic temperature, blood oxygen saturation (SaO2), and vigilance were recorded. Urinal/salivary samples were collected and subjected to cortisol or cortisone analysis, and plasma samples were subjected to transcriptomic analysis of circular RNA (circRNA) expression using microarray. Plasma neurotransmitters were measured by targeted metabolic analysis, and the levels of inflammatory factors were assessed by antibody microarray. Results The volunteers showed significantly increased sleepiness and decreased vigilance during SD, and the changes in circadian rhythm and plasma biochemistry were observed. The plasma calcium (p = 0.0007) was induced by SD, while ischaemia-modified albumin (IMA, p = 0.0030) and total bile acid (TBA, p = 0.0157) decreased. Differentially expressed circRNAs in plasma were identified, which are involved in multiple signaling pathways including neuronal regulation and immunity. Accordingly, SD induced a decrease in 3-hydroxybutyric acid (3OBH, p = 0.0002) and an increase in thyroxine (T4, p < 0.0001) in plasma. The plasma anti-inflammatory cytokine IL-10 was downregulated while other ten inflammatory factors were upregulated. Conclusion This study demonstrates that SD influences biochemical, physiological, cognitive variables, and the significantly changed variables may serve as candidates of SD markers. These findings may further our understanding of the detrimental consequence of sleep disturbance at multiple levels.
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Affiliation(s)
- Shiqi Liu
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
| | - Xiaohong Ma
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
| | - Ying Chen
- Engineering Research Center of Human Circadian Rhythm and Sleep, Space Science and Technology Institute, Shenzhen, China
| | - Yuanyuan Zhao
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
| | - Rujia Luo
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
| | - Zhouying Wu
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
| | - Yicheng Li
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
| | - Yongyu Qian
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
| | - Wenwen Wang
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
| | - Shuohan Dong
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
| | - Zengxuan Zhou
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
| | - Silin Li
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
| | - Yi Xiao
- National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing, China
| | - Xinhai Zhu
- Sun Yat-sen University Instrumental Analysis & Research Center, Sun Yat-sen University, Guangzhou, China
| | - Yu Tian
- National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing, China
| | - Jinhu Guo
- School of Life Sciences, Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, China
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Jiang Y, Lin C, Xu M, Zhu T, Li X, Wang W. Differences and Risk Factors of Peripheral Blood Immune Cells in Patients with Obstructive Sleep Apnea. Nat Sci Sleep 2024; 16:737-749. [PMID: 38882924 PMCID: PMC11178088 DOI: 10.2147/nss.s458098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 05/29/2024] [Indexed: 06/18/2024] Open
Abstract
Introduction Obstructive sleep apnea (OSA) is a respiratory disorder characterized by chronic intermittent hypoxia and fragmented sleep, leading to inflammatory response and oxidative stress. However, the differences in immune inflammatory response in OSA patients with different severity remain unclear. Purpose This study aims to examine the differences in peripheral blood immune cells and their risk factors in OSA patients. Patients and Methods A total of 277 snoring patients from the Sleep Respiratory Disorder Monitoring Center of Zhongnan Hospital of Wuhan University were recruited in this study. According to the diagnosis and severity criteria of OSA, the included patients were further divided into simple snoring, mild, moderate, and severe groups. Peripheral blood immune cell counts including white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cells, platelets, and polysomnography indicators were collected from the patients. Results Compared with simple snoring patients, the OSA patients had increased circular monocyte and basophil count levels. In addition, correlation analysis results indicated that monocyte count was positively associated with chronic obstructive pulmonary disease (COPD), smoking, apnea-hypopnea index (AHI), the longest apnea duration, and Oxygen desaturation index (ODI), and negatively correlated with average SpO2 in snoring patients. Finally, multiple linear regression analysis revealed that AHI, COPD, smoking, and maximum heart rate were independent predictors of monocyte count. Conclusion OSA patients had a significant increase in their peripheral blood monocyte count. AHI, COPD, smoking, and maximum heart rate were risk factors for increased peripheral blood monocyte count in OSA patients. These findings suggest that peripheral blood monocytes can be considered an inflammatory biomarker of OSA.
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Affiliation(s)
- Ying Jiang
- Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China
| | - Chuankai Lin
- Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China
| | - Min Xu
- Medical and Nursing School, Wuhan Railway Vocational College of Technology, Wuhan, 430205, People's Republic of China
| | - Taiwen Zhu
- Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China
| | - Xuhong Li
- Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China
| | - Wei Wang
- Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China
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Yu M, Hao Z, Xu L, Zhao L, Wen Y, Han F, Gao X. Differences in Polysomnographic and Craniofacial Characteristics of Catathrenia Phenotypes: A Cluster Analysis. Nat Sci Sleep 2024; 16:625-638. [PMID: 38831958 PMCID: PMC11144656 DOI: 10.2147/nss.s455705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 05/04/2024] [Indexed: 06/05/2024] Open
Abstract
Purpose Catathrenia is a rare sleeping disorder characterized by repetitive nocturnal groaning during prolonged expirations. Patients with catathrenia had heterogeneous polysomnographic, comorbidity, craniofacial characteristics, and responses to treatment. Identifying phenotypes of catathrenia might benefit the exploration of etiology and personalized therapy. Patients and Methods Sixty-six patients diagnosed with catathrenia by full-night audio/video polysomnography seeking treatment with mandibular advancement devices (MAD) or continuous positive airway pressure (CPAP) were included in the cohort. Polysomnographic characteristics including sleep architecture, respiratory, groaning, and arousal events were analyzed. Three-dimensional (3D) and 2D craniofacial hard tissue and upper airway structures were evaluated with cone-beam computed tomography and lateral cephalometry. Phenotypes of catathrenia were identified by K-mean cluster analysis, and inter-group comparisons were assessed. Results Two distinct clusters of catathrenia were identified: cluster 1 (n=17) was characterized to have more males (71%), a longer average duration of groaning events (18.5±4.8 and 12.8±5.7s, p=0.005), and broader upper airway (volume 41,386±10,543 and 26,661±6700 mm3, p<0.001); cluster 2 (n=49) was characterized to have more females (73%), higher respiratory disturbance index (RDI) (median 1.0 [0.3, 2.0] and 5.2 [1.2, 13.3]/h, p=0.009), more respiratory effort-related arousals (RERA)(1 [1, 109] and 32 [13, 57)], p=0.005), smaller upper airway (cross-sectional area of velopharynx 512±87 and 339±84 mm2, p<0.001) and better response to treatment (41.2% and 82.6%, p=0.004). Conclusion Two distinct phenotypes were identified in patients with catathrenia, primary catathrenia, and catathrenia associated with upper airway obstruction, suggesting respiratory events and upper airway structures might be related to the etiology of catathrenia, with implications for its treatment.
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Affiliation(s)
- Min Yu
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People’s Republic of China
- Center for Oral Therapy of Sleep Apnea, Peking University Hospital of Stomatology, Beijing, People’s Republic of China
- National Center for Stomatology, Beijing, 100081, People’s Republic of China
| | - Zeliang Hao
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People’s Republic of China
- Center for Oral Therapy of Sleep Apnea, Peking University Hospital of Stomatology, Beijing, People’s Republic of China
- National Center for Stomatology, Beijing, 100081, People’s Republic of China
| | - Liyue Xu
- Sleep Division, Peking University People’s Hospital, Beijing, People’s Republic of China
| | - Long Zhao
- Sleep Division, Peking University People’s Hospital, Beijing, People’s Republic of China
| | - Yongfei Wen
- Sleep Division, Peking University People’s Hospital, Beijing, People’s Republic of China
| | - Fang Han
- Sleep Division, Peking University People’s Hospital, Beijing, People’s Republic of China
| | - Xuemei Gao
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People’s Republic of China
- Center for Oral Therapy of Sleep Apnea, Peking University Hospital of Stomatology, Beijing, People’s Republic of China
- National Center for Stomatology, Beijing, 100081, People’s Republic of China
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9
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Liang Y, Lv Y, Qin J, Deng W. Network Pharmacology Analysis of the Potential Pharmacological Mechanism of a Sleep Cocktail. Biomolecules 2024; 14:630. [PMID: 38927034 PMCID: PMC11201840 DOI: 10.3390/biom14060630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 05/22/2024] [Accepted: 05/24/2024] [Indexed: 06/28/2024] Open
Abstract
Insomnia, also known as sleeplessness, is a sleep disorder due to which people have trouble sleeping, followed by daytime sleepiness, low energy, irritability, and a depressed mood. It may result in an increased risk of accidents of all kinds as well as problems focusing and learning. Dietary supplements have become popular products for alleviating insomnia, while the lenient requirements for pre-market research result in unintelligible mechanisms of different combinations of dietary supplements. In this study, we aim to systematically identify the molecular mechanisms of a sleep cocktail's pharmacological effects based on findings from network pharmacology and molecular docking. A total of 249 targets of the sleep cocktail for the treatment of insomnia were identified and enrichment analysis revealed multiple pathways involved in the nervous system and inflammation. Protein-protein interaction (PPI) network analysis and molecular complex detection (MCODE) analysis yielded 10 hub genes, including AKT1, ADORA1, BCL2, CREB1, IL6, JUN, RELA, STAT3, TNF, and TP53. Results from weighted correlation network analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of insomnia-related transcriptome data from peripheral blood mononuclear cells (PBMCs) showed that a sleep cocktail may also ease insomnia via regulating the inflammatory response. Molecular docking results reveal good affinity of Sleep Cocktail to 9 selected key targets. It is noteworthy that the crucial target HSP90AA1 binds to melatonin most stably, which was further validated by MD simulation.
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Affiliation(s)
| | | | - Jing Qin
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China; (Y.L.); (Y.L.)
| | - Wenbin Deng
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China; (Y.L.); (Y.L.)
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10
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Sabot D, Lovegrove R, Stapleton P. The association between sleep quality and telomere length: A systematic literature review. Brain Behav Immun Health 2023; 28:100577. [PMID: 36691437 PMCID: PMC9860369 DOI: 10.1016/j.bbih.2022.100577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 12/20/2022] [Indexed: 01/10/2023] Open
Abstract
Several sleep parameters present an elevated risk for processes that contribute to cellular aging. Short sleep duration, sleep apnoea, and insomnia are significantly associated with shorter telomeres, a biological marker of cellular aging. However, there has been no review or analysis of studies that have examined the association between the psychological construct of sleep quality and telomere length. The present study aimed to provide a systematic review of the association between sleep quality and telomere length. A systematic review of English articles was conducted using MEDLINE/PubMed, PsycINFO, Google Scholar, and Web of Science electronic databases, with the final search conducted on 3rd September 2021. Search terms included sleep quality, poor sleep, insomnia, sleep difficulties, sleep issue*, non-restorative sleep, telomere*, cellular aging, and immune cell telomere length. Study eligibility criteria included human participants aged 18 years or older and a reproducible methodology. Study appraisal and synthesis were completed using a systematic search in line with a PICOS approach (P = Patient, problem, or population; I = Intervention, prognostic factor, exposure; C = Comparison, control, or comparator; O = Outcomes; S = Study designs). Twenty-two studies met review inclusion criteria. Qualitative synthesis of the literature indicated insufficient evidence overall to support a significant association between sleep quality and telomere length. Limitations across studies were addressed, such as the assessment of examined constructs. Findings highlight important targets for future research, including the standardised operationalisation of the sleep quality construct and experimental study designs. Research in this area has clinical significance by identifying possible mechanisms that increase the risk for age-related disease and mortality. PROSPERO Registration No.: CRD 42021233139.
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Affiliation(s)
- Debbie Sabot
- School of Psychology, Faculty of Society and Design, Bond University, Australia
| | - Rhianna Lovegrove
- School of Psychology, Faculty of Society and Design, Bond University, Australia
| | - Peta Stapleton
- School of Psychology, Faculty of Society and Design, Bond University, Australia
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11
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Kourbanova K, Alexandre C, Latremoliere A. Effect of sleep loss on pain-New conceptual and mechanistic avenues. Front Neurosci 2022; 16:1009902. [PMID: 36605555 PMCID: PMC9807925 DOI: 10.3389/fnins.2022.1009902] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 11/29/2022] [Indexed: 12/24/2022] Open
Abstract
Introduction Sleep disturbances increase pain sensitivity in clinical and preclinical settings, but the precise mechanisms are unknown. This represents a major public health issue because of the growing sleep deficiency epidemic fueled by modern lifestyle. To understand the neural pathways at the intersection between sleep and pain processes, it is critical to determine the precise nature of the sleep disruptions that increase pain and the specific component of the pain response that is targeted. Methods We performed a review of the literature about sleep disturbances and pain sensitivity in humans and rodents by taking into consideration the targeted sleep stage (REMS, non-NREMS, or both), the amount of sleep lost, and the different types of sleep disruptions (partial or total sleep loss, duration, sleep fragmentation or interruptions), and how these differences might affect distinct components of the pain response. Results We find that the effects of sleep disturbances on pain are highly conserved among species. The major driver for pain hypersensitivity appears to be the total amount of sleep lost, while REMS loss by itself does not seem to have a direct effect on pain sensitivity. Sleep loss caused by extended wakefulness preferentially increases pain perception, whereas interrupted and limited sleep strongly dysregulates descending controls such as DNIC, especially in women. Discussion We discuss the possible mechanisms involved, including an increase in inflammatory processes, a loss of nociceptive inhibitory pathways, and a defect in the cognitive processing of noxious input.
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Affiliation(s)
- Kamila Kourbanova
- Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD, United States
- Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Chloe Alexandre
- Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD, United States
- Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Alban Latremoliere
- Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD, United States
- Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, United States
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12
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Quercetin ameliorates memory impairment by inhibiting abnormal microglial activation in a mouse model of paradoxical sleep deprivation. Biochem Biophys Res Commun 2022; 632:10-16. [DOI: 10.1016/j.bbrc.2022.09.088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 09/12/2022] [Accepted: 09/22/2022] [Indexed: 11/18/2022]
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13
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Mendez N, Halabi D, Salazar-Petres ER, Vergara K, Corvalan F, Richter HG, Bastidas C, Bascur P, Ehrenfeld P, Seron-Ferre M, Torres-Farfan C. Maternal melatonin treatment rescues endocrine, inflammatory, and transcriptional deregulation in the adult rat female offspring from gestational chronodisruption. Front Neurosci 2022; 16:1039977. [PMID: 36507347 PMCID: PMC9727156 DOI: 10.3389/fnins.2022.1039977] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 10/31/2022] [Indexed: 11/24/2022] Open
Abstract
Introduction Gestational chronodisruption impact maternal circadian rhythms, inhibiting the nocturnal increase of melatonin, a critical hormone that contributes to maternal changes adaptation, entrains circadian rhythms, and prepares the fetus for birth and successful health in adulthood. In rats, we know that gestational chronodisruption by maternal chronic photoperiod shifting (CPS) impaired maternal melatonin levels and resulted in long-term metabolic and cardiovascular effects in adult male offspring. Here, we investigated the consequences of CPS on mother and adult female offspring and explored the effects of melatonin maternal supplementation. Also, we tested whether maternal melatonin administration during gestational chronodisruption rescues maternal circadian rhythms, pregnancy outcomes, and transcriptional functions in adult female offspring. Methods Female rats raised and maintained in photoperiod 12:12 light: dark were mated and separated into three groups: (a) Control photoperiod 12:12 (LD); (b) CPS photoperiod; and (c) CPS+Mel mothers supplemented with melatonin in the drinking water throughout gestation. In the mother, we evaluated maternal circadian rhythms by telemetry and pregnancy outcomes, in the long-term, we study adult female offspring by evaluating endocrine and inflammatory markers and the mRNA expression of functional genes involved in adrenal, cardiac, and renal function. Results In the mothers, CPS disrupted circadian rhythms of locomotor activity, body temperature, and heart rate and increased gestational length by almost 12-h and birth weight by 12%, all of which were rescued by maternal melatonin administration. In the female offspring, we found blunted day/night differences in circulating levels of melatonin and corticosterone, abnormal patterns of pro-inflammatory cytokines Interleukin-1a (IL1a), Interleukin-6 (IL6), and Interleukin-10 (IL10); and differential expression in 18 out of 24 adrenal, cardiac, and renal mRNAs evaluated. Conclusion Maternal melatonin contributed to maintaining the maternal circadian rhythms in mothers exposed to CPS, and the re-establishing the expression of 60% of the altered mRNAs to control levels in the female offspring. Although we did not analyze the effects on kidney, adrenal, and heart physiology, our results reinforce the idea that altered maternal circadian rhythms, resulting from exposure to light at night, should be a mechanism involved in the programming of Non-Communicable Diseases.
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Affiliation(s)
- Natalia Mendez
- Laboratorio de Cronobiología del Desarrollo, Facultad de Medicina, Instituto de Anatomía, Histología y Patología, Universidad Austral de Chile, Valdivia, Chile
| | - Diego Halabi
- School of Dentistry, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile
| | - Esteban Roberto Salazar-Petres
- Laboratorio de Cronobiología del Desarrollo, Facultad de Medicina, Instituto de Anatomía, Histología y Patología, Universidad Austral de Chile, Valdivia, Chile
| | - Karina Vergara
- Laboratorio de Cronobiología del Desarrollo, Facultad de Medicina, Instituto de Anatomía, Histología y Patología, Universidad Austral de Chile, Valdivia, Chile
| | - Fernando Corvalan
- Laboratorio de Cronobiología del Desarrollo, Facultad de Medicina, Instituto de Anatomía, Histología y Patología, Universidad Austral de Chile, Valdivia, Chile
| | - Hans G. Richter
- Laboratorio de Cronobiología del Desarrollo, Facultad de Medicina, Instituto de Anatomía, Histología y Patología, Universidad Austral de Chile, Valdivia, Chile
| | - Carla Bastidas
- Laboratorio de Cronobiología del Desarrollo, Facultad de Medicina, Instituto de Anatomía, Histología y Patología, Universidad Austral de Chile, Valdivia, Chile
| | - Pía Bascur
- Laboratorio de Cronobiología del Desarrollo, Facultad de Medicina, Instituto de Anatomía, Histología y Patología, Universidad Austral de Chile, Valdivia, Chile
| | - Pamela Ehrenfeld
- Laboratorio de Cronobiología del Desarrollo, Facultad de Medicina, Instituto de Anatomía, Histología y Patología, Universidad Austral de Chile, Valdivia, Chile,Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile
| | - Maria Seron-Ferre
- Programa de Fisiopatología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Claudia Torres-Farfan
- Laboratorio de Cronobiología del Desarrollo, Facultad de Medicina, Instituto de Anatomía, Histología y Patología, Universidad Austral de Chile, Valdivia, Chile,Centro Interdisciplinario de Estudios del Sistema Nervioso (CISNe), Universidad Austral de Chile, Valdivia, Chile,*Correspondence: Claudia Torres-Farfan,
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14
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Piber D, Cho JH, Lee O, Lamkin DM, Olmstead R, Irwin MR. Sleep disturbance and activation of cellular and transcriptional mechanisms of inflammation in older adults. Brain Behav Immun 2022; 106:67-75. [PMID: 35953022 DOI: 10.1016/j.bbi.2022.08.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 08/03/2022] [Accepted: 08/05/2022] [Indexed: 10/31/2022] Open
Abstract
BACKGROUND Sleep disturbance, including poor subjective sleep quality and insomnia disorder, is common in older adults and associated with increases in age-related morbidity risk. Accumulating evidence implicates inflammation as an underlying mechanism. In two complementary studies, we examined whether sleep disturbance is associated with activation of cellular and transcriptional mechanisms of inflammation in older adults. METHODS Study 1 examined whether healthy older adults with poor subjective sleep quality (n = 62), compared to those with good subjective sleep quality (n = 101), differed in monocytic production of interleukin (IL)-6 and/or tumor necrosis factor (TNF)-α following stimulation with lipopolysaccharide. Study 2 examined whether older adults with insomnia disorder (n = 17), compared to those without insomnia disorder (n = 25), differed in the regulation of transcription factors (TFs) related to immune activation (i.e., nuclear factor-κB/Rel family), sympathetic nervous system (SNS) activity (i.e., cAMP-response element-binding protein), hypothalamic-pituitary-adrenal (HPA) axis activity (i.e., glucocorticoid receptor) and anti-viral responses (i.e., interferon-regulatory factor/interferon-stimulated response element) assessed in peripheral blood mononuclear cells. RESULTS In Study 1, older adults with poor subjective sleep quality, compared to those with good subjective sleep quality, showed higher percentages of stimulated monocytes producing IL-6 only (25.4 ± 16.8 % vs 20.4 ± 13.9 %; p < 0.05, ηp2 = 0.03), producing TNF-α only (37.6 ± 13.1 % vs 31.2 ± 14.3 %; p < 0.01, ηp2 = 0.05), and co-producing IL-6/TNF-α simultaneously (17.8 ± 11.7 % vs 13.9 ± 9.6 %; p < 0.05, ηp2 = 0.03). In Study 2, older adults with insomnia disorder, compared to those without insomnia disorder, showed higher TF activity related to immune activation (p's < 0.05) and SNS function (p's < 0.001), along with lower TF activity related to HPA axis function (p's < 0.05). CONCLUSION In older adults, poor subjective sleep quality and insomnia diagnosis are associated with increases in monocytic cytokine production and changes in TF activity related to immune activation, SNS function, and HPA axis function. Activation of markers of cellular and transcriptional inflammation might contribute to the link between sleep disturbance and age-related morbidity risk.
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Affiliation(s)
- Dominique Piber
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA; Department of Psychiatry and Neurosciences, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany
| | - Joshua H Cho
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Olivia Lee
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Donald M Lamkin
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA
| | - Richard Olmstead
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Michael R Irwin
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA; Department of Psychology, College of Arts and Sciences, UCLA, Los Angeles, CA, USA.
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15
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Wei R, Duan X, Guo L. Effects of sleep deprivation on coronary heart disease. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY 2022; 26:297-305. [PMID: 36039730 PMCID: PMC9437362 DOI: 10.4196/kjpp.2022.26.5.297] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 03/06/2022] [Accepted: 06/10/2022] [Indexed: 11/30/2022]
Abstract
The presence of artificial light enables humans to be active 24 h a day. Many people across the globe live in a social culture that encourages staying up late to meet the demands of various activities, such as work and school. Sleep deprivation (SD) is a severe health problem in modern society. Meanwhile, as with cardiometabolic disease, there was an obvious tendency that coronary heart disease (CHD) to become a global epidemic chronic disease. Specifically, SD can significantly increase the morbidity and mortality of CHD. However, the underlying mechanisms responsible for the effects of SD on CHD are multilayered and complex. Inflammatory response, lipid metabolism, oxidative stress, and endothelial function all contribute to cardiovascular lesions. In this review, the effects of SD on CHD development are summarized, and SD-related pathogenesis of coronary artery lesions is discussed. In general, early assessment of SD played a vital role in preventing the harmful consequences of CHD.
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Affiliation(s)
- Ran Wei
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Peking University Fifth School of Clinical Medicine, Beijing, China
| | - Xiaoye Duan
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Lixin Guo
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Peking University Fifth School of Clinical Medicine, Beijing, China
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16
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Walker WE. GOODNIGHT, SLEEP TIGHT, DON'T LET THE MICROBES BITE: A REVIEW OF SLEEP AND ITS EFFECTS ON SEPSIS AND INFLAMMATION. Shock 2022; 58:189-195. [PMID: 35959798 PMCID: PMC9489678 DOI: 10.1097/shk.0000000000001976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
ABSTRACT Sleep is a restorative biological process that is crucial for health and homeostasis. However, patient sleep is frequently interrupted in the hospital environment, particularly within the intensive care unit. Suboptimal sleep may alter the immune response and make patients more vulnerable to infection and sepsis. In addition, hospitalized patients with sepsis experience altered sleep relative to patients without infectious disease, suggesting a bidirectional interplay. Preclinical studies have generated complementary findings, and together, these studies have expanded our mechanistic understanding. This review article summarizes clinical and preclinical studies describing how sleep affects inflammation and the host's susceptibility to infection. We also highlight potential strategies to reverse the detrimental effects of sleep interruption in the intensive care unit.
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Affiliation(s)
- Wendy E. Walker
- Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX
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17
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Kuna K, Szewczyk K, Gabryelska A, Białasiewicz P, Ditmer M, Strzelecki D, Sochal M. Potential Role of Sleep Deficiency in Inducing Immune Dysfunction. Biomedicines 2022; 10:biomedicines10092159. [PMID: 36140260 PMCID: PMC9496201 DOI: 10.3390/biomedicines10092159] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 08/27/2022] [Accepted: 08/30/2022] [Indexed: 11/16/2022] Open
Abstract
Sleep deficiency and insomnia deteriorate the quality of patients’ lives, yet the exact influence of these factors on the immune system has only begun to gain interest in recent years. Growing evidence shows that insomnia is a risk factor for numerous diseases, including common infections and autoimmune diseases. Levels of inflammatory markers also seem to be abnormal in sleep deficient individuals, which may lead to low-grade inflammation. The interpretation of studies is difficult due to the equivocal term “sleep disturbances,” as well as due to the various criteria used in studies. This narrative review aims to summarize the available knowledge regarding the bidirectional influence of the immune system and sleep disturbances.
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Affiliation(s)
- Kasper Kuna
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland
| | - Krzysztof Szewczyk
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland
| | - Agata Gabryelska
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland
| | - Piotr Białasiewicz
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland
| | - Marta Ditmer
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland
| | - Dominik Strzelecki
- Department of Affective and Psychotic Disorders, Medical University of Lodz, 92-213 Lodz, Poland
| | - Marcin Sochal
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland
- Correspondence: ; Tel.: +48-42-678-18-00
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18
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Irwin MR. Sleep disruption induces activation of inflammation and heightens risk for infectious disease: Role of impairments in thermoregulation and elevated ambient temperature. Temperature (Austin) 2022; 10:198-234. [PMID: 37332305 PMCID: PMC10274531 DOI: 10.1080/23328940.2022.2109932] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 07/25/2022] [Accepted: 07/30/2022] [Indexed: 10/15/2022] Open
Abstract
Thermoregulation and sleep are tightly coordinated, with evidence that impairments in thermoregulation as well as increases in ambient temperature increase the risk of sleep disturbance. As a period of rest and low demand for metabolic resources, sleep functions to support host responses to prior immunological challenges. In addition by priming the innate immune response, sleep prepares the body for injury or infection which might occur the following day. However when sleep is disrupted, this phasic organization between nocturnal sleep and the immune system becomes misaligned, cellular and genomic markers of inflammation are activated, and increases of proinflammatory cytokines shift from the nighttime to the day. Moreover, when sleep disturbance is perpetuated due to thermal factors such as elevated ambient temperature, the beneficial crosstalk between sleep and immune system becomes further imbalanced. Elevations in proinflammatory cytokines have reciprocal effects and induce sleep fragmentation with decreases in sleep efficiency, decreases in deep sleep, and increases in rapid eye movement sleep, further fomenting inflammation and inflammatory disease risk. Under these conditions, sleep disturbance has additional potent effects to decrease adaptive immune response, impair vaccine responses, and increase vulnerability to infectious disease. Behavioral interventions effectively treat insomnia and reverse systemic and cellular inflammation. Further, insomnia treatment redirects the misaligned inflammatory- and adaptive immune transcriptional profiles with the potential to mitigate risk of inflammation-related cardiovascular, neurodegenerative, and mental health diseases, as well as susceptibility to infectious disease.
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Affiliation(s)
- Michael R. Irwin
- University of California, Los Angeles – Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, Los Angeles, California, USA
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19
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Arleevskaya M, Takha E, Petrov S, Kazarian G, Renaudineau Y, Brooks W, Larionova R, Korovina M, Valeeva A, Shuralev E, Mukminov M, Kravtsova O, Novikov A. Interplay of Environmental, Individual and Genetic Factors in Rheumatoid Arthritis Provocation. Int J Mol Sci 2022; 23:ijms23158140. [PMID: 35897715 PMCID: PMC9329780 DOI: 10.3390/ijms23158140] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/18/2022] [Accepted: 07/19/2022] [Indexed: 02/05/2023] Open
Abstract
In this review, we explore systemization of knowledge about the triggering effects of non-genetic factors in pathogenic mechanisms that contribute to the development of rheumatoid arthritis (RA). Possible mechanisms involving environmental and individual factors in RA pathogenesis were analyzed, namely, infections, mental stress, sleep deprivation ecology, age, perinatal and gender factors, eating habits, obesity and smoking. The non-genetic factors modulate basic processes in the body with the impact of these factors being non-specific, but these common challenges may be decisive for advancement of the disease in the predisposed body at risk for RA. The provocation of this particular disease is associated with the presence of congenital loci minoris resistentia. The more frequent non-genetic factors form tangles of interdependent relationships and, thereby, several interdependent external factors hit one vulnerable basic process at once, either provoking or reinforcing each other. Understanding the specific mechanisms by which environmental and individual factors impact an individual under RA risk in the preclinical stages can contribute to early disease diagnosis and, if the factor is modifiable, might be useful for the prevention or delay of its development.
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Affiliation(s)
- Marina Arleevskaya
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia;
- Correspondence: ; Tel.: +7-89172-886-679; Fax: +7-843-238-5413
| | - Elena Takha
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
| | - Sergey Petrov
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
- Institute of Environmental Sciences, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | - Gevorg Kazarian
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
| | - Yves Renaudineau
- Department of Immunology, CHU Toulouse, INSERM U1291, CNRS U5051, University Toulouse IIII, 31000 Toulouse, France;
| | - Wesley Brooks
- Department of Chemistry, University of South Florida, Tampa, FL 33620, USA;
| | - Regina Larionova
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
| | - Marina Korovina
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia;
| | - Anna Valeeva
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
| | - Eduard Shuralev
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
- Institute of Environmental Sciences, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | - Malik Mukminov
- Central Research Laboratory, Kazan State Medical Academy, 420012 Kazan, Russia; (E.T.); (S.P.); (G.K.); (R.L.); (M.K.); (A.V.); (E.S.); (M.M.)
- Institute of Environmental Sciences, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | - Olga Kravtsova
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia;
| | - Andrey Novikov
- Mathematical Center, Sobolev Instiute of Mathematics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia;
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20
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Wan Y, Gao W, Zhou K, Liu X, Jiang W, Xue R, Wu W. Role of IGF-1 in neuroinflammation and cognition deficits induced by sleep deprivation. Neurosci Lett 2022; 776:136575. [PMID: 35276231 DOI: 10.1016/j.neulet.2022.136575] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 03/05/2022] [Accepted: 03/07/2022] [Indexed: 12/25/2022]
Abstract
Sleep deprivation negatively influences cognition, however, the regulatory mechanisms to counteract this effect have not been identified. IGF-1 has been shown to be anti-inflammatory and neuroprotective in CNS injury models. In this study, we determined the impact of IGF-1 on brain injury and inflammation while modeling sleep deprivation. We found that IGF-1 was downregulated in human peripheral blood and in mice subjected to sleep deprivation for 5 days, with reduced activation of the downstream PI3K/AKT/GSK-3β pathway in mice brains. In addition, we found reduced levels of the anti-apoptosis enzyme Bcl-2 and increased levels of pro-apoptosis enzyme Caspase-9 expression, together with increased pro-inflammatory factors. The administration of IGF-1 after sleep deprivation induced activation of the PI3K/AKT/GSK-3β pathway, reversed changes in Bcl-2, Caspase-9, and pro-inflammatory factors, and alleviated cognitive impairment. Notably, IGF-1 also induced activation of the PI3K/AKT/GSK-3β pathway, and displayed anti-apoptosis and anti-inflammatory properties under normal sleep conditions,while IGF-1 did not improve the cognition under normal sleep conditions. These results suggest that the IGF-1/PI3K/AKT/GSK-3β pathway is involved in the regulation of cognitive function after sleep deprivation through modulation of apoptosis and inflammatory response. IGF-1 could be a viable therapeutic target, though further investigation is required to better understand its role in sleep deprivation.
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Affiliation(s)
- Yahui Wan
- Departments of Neurology, Tianjin Medical University General Hospital Airport Hospital, Tianjin 300308, China.
| | - Wei Gao
- Departments of Neurology, Beijing Pinggu District Hospital, Beijing 101200, China
| | - Kaili Zhou
- Departments of Neurology, Tianjin Medical University General Hospital Airport Hospital, Tianjin 300308, China
| | - Xuan Liu
- Departments of Neurology, Tianjin Medical University General Hospital Airport Hospital, Tianjin 300308, China
| | - Wei Jiang
- Departments of Neurology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Rong Xue
- Departments of Neurology, Tianjin Medical University General Hospital, Tianjin 300052, China.
| | - Wei Wu
- Departments of Neurology, Tianjin Medical University General Hospital, Tianjin 300052, China.
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21
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Garbarino S, Lanteri P, Bragazzi NL, Magnavita N, Scoditti E. Role of sleep deprivation in immune-related disease risk and outcomes. Commun Biol 2021; 4:1304. [PMID: 34795404 PMCID: PMC8602722 DOI: 10.1038/s42003-021-02825-4] [Citation(s) in RCA: 199] [Impact Index Per Article: 49.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 10/26/2021] [Indexed: 12/11/2022] Open
Abstract
Modern societies are experiencing an increasing trend of reduced sleep duration, with nocturnal sleeping time below the recommended ranges for health. Epidemiological and laboratory studies have demonstrated detrimental effects of sleep deprivation on health. Sleep exerts an immune-supportive function, promoting host defense against infection and inflammatory insults. Sleep deprivation has been associated with alterations of innate and adaptive immune parameters, leading to a chronic inflammatory state and an increased risk for infectious/inflammatory pathologies, including cardiometabolic, neoplastic, autoimmune and neurodegenerative diseases. Here, we review recent advancements on the immune responses to sleep deprivation as evidenced by experimental and epidemiological studies, the pathophysiology, and the role for the sleep deprivation-induced immune changes in increasing the risk for chronic diseases. Gaps in knowledge and methodological pitfalls still remain. Further understanding of the causal relationship between sleep deprivation and immune deregulation would help to identify individuals at risk for disease and to prevent adverse health outcomes.
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Affiliation(s)
- Sergio Garbarino
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal/Child Sciences, University of Genoa, 16132, Genoa, Italy.
| | - Paola Lanteri
- Neurophysiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Nicola Luigi Bragazzi
- Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, ON, M3J 1P3, Canada
| | - Nicola Magnavita
- Postgraduate School of Occupational Medicine, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
- Department of Woman/Child and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy
| | - Egeria Scoditti
- National Research Council (CNR), Institute of Clinical Physiology (IFC), 73100, Lecce, Italy
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22
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Zhang Y, Cheng L, Liu Y, Wu Z, Weng P. The Intestinal Microbiota Links Tea Polyphenols with the Regulation of Mood and Sleep to Improve Immunity. FOOD REVIEWS INTERNATIONAL 2021. [DOI: 10.1080/87559129.2021.1934007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Yuting Zhang
- Department of Food Science and Engineering, Ningbo University, Ningbo, P.R. China
| | - Lu Cheng
- Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, New Jersey, USA
| | - Yanan Liu
- Department of Food Science and Engineering, Ningbo University, Ningbo, P.R. China
| | - Zufang Wu
- Department of Food Science and Engineering, Ningbo University, Ningbo, P.R. China
| | - Peifang Weng
- Department of Food Science and Engineering, Ningbo University, Ningbo, P.R. China
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23
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Halabi D, Richter HG, Mendez N, Kähne T, Spichiger C, Salazar E, Torres F, Vergara K, Seron-Ferre M, Torres-Farfan C. Maternal Chronodisruption Throughout Pregnancy Impairs Glucose Homeostasis and Adipose Tissue Physiology in the Male Rat Offspring. Front Endocrinol (Lausanne) 2021; 12:678468. [PMID: 34484111 PMCID: PMC8415792 DOI: 10.3389/fendo.2021.678468] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 07/19/2021] [Indexed: 11/25/2022] Open
Abstract
Compelling evidence in rats support the idea that gestational chronodisruption induces major changes in maternal circadian rhythms and fetal development and that these changes impact adult life at many physiological levels. Using a model of chronic photoperiod shifting throughout gestation (CPS), in which pregnant female rats (Sprague-Dawley strain; n = 16 per group) were exposed to lighting schedule manipulation every 3-4 days reversing the photoperiod completely or light/dark photoperiod (12/12; LD), we explored in the adult rat male offspring body weight gain, glucose homeostasis, adipose tissue content, adipose tissue response to norepinephrine (NE), and adipose tissue proteomic in the basal condition with standard diet (SD) and in response to high-fat diet (HFD). In adult CPS male (100-200 days old; n = 8 per group), we found increasing body weight, under SD and adiposity. Also, we found an increased response to intraperitoneal glucose (IGTT). After 12 weeks of HFD, white adipose tissue depots in CPS offspring were increased further, and higher IGTT and lower intraperitoneal insulin tolerance response were found, despite the lack of changes in food intake. In in vitro experiments, we observed that adipose tissue (WAT and BAT) glycerol response to NE from CPS offspring was decreased, and it was completely abolished by HFD. At the proteomic level, in CPS adipose tissue, 275 proteins displayed differential expression, compared with LD animals fed with a standard diet. Interestingly, CPS offspring and LD fed with HFD showed 20 proteins in common (2 upregulated and 18 downregulated). Based on these common proteins, the IPA analysis found that two functional pathways were significantly altered by CPS: network 1 (AKT/ERK) and network 2 (TNF/IL4; data are available via ProteomeXchange with identifier PXD026315). The present data show that gestational chronodisruption induced deleterious effects in adipose tissue recruitment and function, supporting the idea that adipose tissue function was programmed in utero by gestational chronodisruption, inducing deficient metabolic responses that persist into adulthood.
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Affiliation(s)
- Diego Halabi
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
- Institute of Dentistry, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
| | - Hans G. Richter
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
| | - Natalia Mendez
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
| | - Thilo Kähne
- Mass Spectrometry for Massive Proteomics, Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Magdeburg, Germany
| | - Carlos Spichiger
- Institute of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Valdivia, Chile
| | - Esteban Salazar
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
| | - Fabiola Torres
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
| | - Karina Vergara
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
| | - Maria Seron-Ferre
- Programa de Fisiopatología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Claudia Torres-Farfan
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
- *Correspondence: Claudia Torres-Farfan,
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24
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Yu M, Wen Y, Xu L, Han F, Gao X. Polysomnographic characteristics and acoustic analysis of catathrenia (nocturnal groaning). Physiol Meas 2020; 41:125012. [PMID: 33296889 DOI: 10.1088/1361-6579/abd235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Catathrenia is a sleep disorder characterized by nocturnal groaning sounds emitted during prolonged expiration. As a rare condition, its polysomnographic findings were inconsistent. We aimed to present polysomnographic characteristics of catathrenia patients and perform acoustic analysis of groaning sounds. APPROACH Twenty-three patients (eight males and 15 females) diagnosed with catathrenia by video-polysomnography were included. They underwent clinical evaluation and physical examination, and answered a questionnaire. Acoustic analyses (oscillograms and spectrograms) of catathrenia and snoring signals were performed by Praat 6.1.09. Sounds were classified according to Yanagihara criteria. MAIN RESULTS The average age of catathrenia patients was 29.6 ± 10.0 years, with a body mass index of 22.3 ± 5.1 kg m-2. A total of 3728 groaning episodes were documented. Catathrenia events of 16 patients (70%) were rapid eye movement (REM)-predominant. The average duration of groaning was 11.4 ± 4.6 s, ranging from 1.3 to 74.9 s. All signals of groaning were rhythmic or semi-rhythmic, classified as type I and type II, respectively, with formants and harmonics. Snoring events were observed in nine patients. Snoring mainly occurred in the non-REM stage, with a duration of less than 1.5 s. Signals of snoring were chaotic, classified as type III, without harmonics. SIGNIFICANCE Catathrenia occurred in all sleep stages but mainly in REM. Durations of groaning varied greatly across patients. Acoustic characteristics of catathrenia were typical. Groaning had rhythmic or semi-rhythmic waveform, formants and harmonics, indicating vocal origin, while snoring had chaotic waveform.
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Affiliation(s)
- Min Yu
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, People's Republic of China
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Godzik C, Crawford S, Ryan E. Feasibility of an online cognitive behavioral therapy program to improve insomnia, mood, and quality of life in bereaved adults ages 55 and older. Geriatr Nurs 2020; 42:99-106. [PMID: 33340917 DOI: 10.1016/j.gerinurse.2020.12.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 12/04/2020] [Accepted: 12/04/2020] [Indexed: 11/19/2022]
Abstract
The aim of the current study was to assess the feasibility and preliminary efficacy of utilizing an online Cognitive Behavioral Therapy for Insomnia (CBT-I) program in bereaved older adults (ages 55 and older). Participants were randomized to receive either a 6-week online CBT-I program or six weeks of online psychoeducational modules on insomnia and grief. The sample included 30 adults with mild to severe symptoms of insomnia. Results suggest that the study was feasible to conduct, as evidenced by the brief 5-week recruitment time, 87% retention rate, and 100% completion rate of the intervention modules. There were no treatment effects by time difference shown in the study and no significant differences in study outcomes were found between the CBT-I and control groups, as both demonstrated similar improvements in insomnia. However, this study suggests that it is feasible to recruit bereaved older adults for an online educational program and successfully administer an online protocol targeting insomnia and well-being.
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Affiliation(s)
- Cassandra Godzik
- Dartmouth College/Dartmouth Hitchcock Medical Center, Dartmouth Centers for Health and Aging, 46 Centerra Parkway, Box 201, Lebanon, New Hampshire 03766 USA.
| | - Sybil Crawford
- University of Massachusetts Medical School, Graduate School of Nursing, 55 North Lake Avenue, Worcester, Massachusetts, 01655 USA
| | - Elizabeth Ryan
- Veterans Association Boston Healthcare System, 150 South Huntington Avenue, Boston, Massachusetts, 02130 USA
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26
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A key role of gut microbiota-vagus nerve/spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration. Life Sci 2020; 265:118736. [PMID: 33176177 DOI: 10.1016/j.lfs.2020.118736] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 10/26/2020] [Accepted: 11/05/2020] [Indexed: 12/15/2022]
Abstract
AIMS Sleep deprivation (SD) correlates with exacerbated systemic inflammation after sepsis. However, the underlying mechanisms remain unclear. This study aimed to evaluate the roles and mechanisms of SD in inflammatory organ injury after lipopolysaccharide (LPS) administration. MAIN METHODS Mice were intraperitoneally injected with LPS followed by 3 consecutive days of SD. The pseudo germ-free (PGF) mice received fecal microbiota transplant by being gavaged with supernatant from fecal suspension of septic mice with or without SD. The subdiaphragmatic vagotomy (SDV) or splenectomy was performed 14 days prior to LPS injection or antibiotics administration. KEY FINDINGS Post-septic SD increased the plasma levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), reduced IL-10 plasma level, increased spleen weight, and promoted inflammatory injury of the lung, liver and kidney. The relative abundance of Proteobacteria and its subgroups were increased after post-septic SD. PGF mice transplanted with fecal bacteria from septic mice subjected to SD developed splenomegaly, systemic inflammation, organ inflammation and damage as their donors did. Intriguingly, SDV abolished the aggravated effects of SD on splenomegaly and inflammatory organ injury in septic mice received SD or in PGF mice transplanted with fecal bacteria from septic mice subjected to SD. Furthermore, splenectomy also abrogated the increase in IL-6 and TNF-α plasma levels and the decrease in IL-10 plasma level in PGF mice transplanted with fecal bacteria from septic mice subjected to SD. SIGNIFICANCE Gut microbiota-vagus nerve axis and gut microbiota-spleen axis play key roles in modulating systemic inflammation induced by SD after LPS administration.
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27
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Sleep, inflammation, and perception of sad facial emotion: A laboratory-based study in older adults. Brain Behav Immun 2020; 89:159-167. [PMID: 32531429 DOI: 10.1016/j.bbi.2020.06.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 06/06/2020] [Accepted: 06/06/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Facial emotion perception (FEP) is pivotal for discriminating salient emotional information. Accumulating data indicate that FEP responses, particularly to sad emotional stimuli, are impaired in depression. This study tests whether sleep disturbance and inflammation, two risk factors for depression, contribute to impaired FEP to sad emotional stimuli. METHODS In older adults (n = 40, 71.7 ± 6.8y, 56.4% female), disturbance of sleep maintenance (i.e., wake time after sleep onset [WASO]) was evaluated by polysomnography. In the morning, plasma concentrations of two markers of systemic inflammation were evaluated (i.e., interleukin [IL]-6, tumor necrosis factor [TNF]-α), followed by two FEP tasks, which assessed delays in emotion recognition (ER) and ratings of perceived emotion intensity (EI) in response to sad facial emotional stimuli, with exploration of FEP responses to happiness and anger. Linear regression models tested whether WASO, IL-6, and TNF-α would be associated with impaired FEP to sad emotional stimuli. In addition, moderation tests examined whether inflammation would moderate the link between sleep disturbance and impaired FEP to sad emotional stimuli. RESULTS Longer WASO predicted longer ER delays (p < 0.05) and lower EI ratings in response to sad faces (p < 0.01). Further, higher TNF-α (p < 0.05) but not IL-6 predicted longer ER delays for sad faces, whereas higher IL-6 (p < 0.01) but not TNF-α predicted lower EI ratings for sad faces. Finally, TNF-α moderated the relationship between longer WASO and longer ER delays to sad faces (p < 0.001), while IL-6 moderated the relationship between longer WASO and lower EI ratings to sad faces (p < 0.01). Neither sleep nor inflammatory measures were associated with FEP responses to happiness or anger. CONCLUSION In older adults, disturbance of sleep maintenance is associated with impaired FEP to sad emotion, a relationship that appears to be moderated by inflammation. These data indicate that sleep disturbance and inflammation converge and contribute to impaired FEP with implications for risk for late-life depression.
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28
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Liew SC, Aung T. Sleep deprivation and its association with diseases- a review. Sleep Med 2020; 77:192-204. [PMID: 32951993 DOI: 10.1016/j.sleep.2020.07.048] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/08/2020] [Accepted: 07/27/2020] [Indexed: 01/02/2023]
Abstract
Sleep deprivation, a consequence of multiple health problems or a cause of many major health risks, is a significant public health concern in this era. In the recent years, numerous reports have been added to the literature to provide explanation and to answer previously unanswered questions on this important topic but comprehensive updates and reviews in this aspect remain scarce. The present study identified 135 papers that investigated the association between sleep deprivation and health risks, including cardiovascular, respiratory, neurological, gastrointestinal, immunology, dermatology, endocrine, and reproductive health. In this review, we aimed to provide insight into the association between sleep deprivation and the development of diseases. We reviewed the latest updates available in the literature and particular attention was paid to reports that detailed all possible causal relationships involving both extrinsic and intrinsic factors that may be relevant to this topic. Various mechanisms by which sleep deprivation may affect health were presented and discussed, and this review hopes to serve as a platform for ideas generation for future research.
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Affiliation(s)
- Siaw Cheok Liew
- Department of Clinical Competence, Perdana University-Royal College of Surgeons in Ireland, Kuala Lumpur, Malaysia.
| | - Thidar Aung
- Department of Biochemistry, Perdana University-Royal College of Surgeons in Ireland, Kuala Lumpur, Malaysia
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29
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Carroll JE, Rentscher KE, Cole SW, Luo JJ, Ramilo O, Webber S, Lamkin DM, Christian LM. Sleep disturbances and inflammatory gene expression among pregnant women: Differential responses by race. Brain Behav Immun 2020; 88:654-660. [PMID: 32360438 PMCID: PMC7526416 DOI: 10.1016/j.bbi.2020.04.065] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 04/20/2020] [Accepted: 04/25/2020] [Indexed: 12/27/2022] Open
Abstract
Excessive inflammation in pregnancy predicts adverse birth outcomes, including shortened gestational length and lower birthweight, with African American women at greater risk. As substantial racial disparities in sleep quality, and evidence that African Americans have increased vulnerability for sleep-induced inflammatory dysregulation, sleep may be a critical, modifiable health behavior that contributes to racial disparities in birth outcomes. The present study examined sleep disturbance as a predictor of genome-wide transcriptome profiles of peripheral blood samples from 103 pregnant women (33 African American, 70 white) assessed at 18.7 ± 7.2 weeks gestation. We hypothesized that pregnant women with significant sleep disturbances would have gene expression profiles indicating over-expression of inflammatory pathways, with greater effects among African American compared to white women. Promoter-based bioinformatics analyses of differentially expressed genes indicated greater activation of NF-кB, AP1, and CREB transcription factors among African American women with sleep disturbances (all p < 0.05), and enhanced activation of AP1, but not NF-кB and reduced CREB activity among white women with sleep disturbances (p < 0.05). Differences in glucocorticoid receptor (GR) activity were also observed, in which African American women with sleep disturbances had reduced GR activity (p < 0.05), but white women with sleep disturbances showed a trend for enhanced GR activity (p = 0.11). Similarly, Interferon Response Factor (IRF) activity was reduced in African American women while increased in white women with sleep disturbances (p < 0.05). The current study provides novel evidence for gene expression related to inflammation, glucocorticoids, and anti-viral immunity among pregnant women with sleep disturbances, with differential effects by race. African Americans showed greater breadth and magnitude in these proinflammatory and anti-viral pathways than whites, with divergence in anti-inflammatory glucocorticoid, proinflammatory adrenergic-mediated cAMP, and anti-viral interferon responses. These data elucidate the role of sleep disturbances in intracellular inflammatory and anti-viral immunity in pregnancy and provide a potential target for intervention.
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Affiliation(s)
- Judith E Carroll
- Cousins Center for Psychoneuroimmunology, Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA.
| | - Kelly E Rentscher
- Cousins Center for Psychoneuroimmunology, Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
| | - Steven W Cole
- Cousins Center for Psychoneuroimmunology, Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
| | - James J Luo
- Cousins Center for Psychoneuroimmunology, Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
| | - Octavio Ramilo
- Department of Psychiatry & Behavioral Health and The Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Shannon Webber
- College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Donald M Lamkin
- Cousins Center for Psychoneuroimmunology, Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA
| | - Lisa M Christian
- Department of Psychiatry & Behavioral Health and The Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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30
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Piber D, Olmstead R, Cho JHJ, Witarama T, Perez C, Dietz N, Seeman TE, Breen EC, Cole SW, Irwin MR. Inflammaging: Age and Systemic, Cellular, and Nuclear Inflammatory Biology in Older Adults. J Gerontol A Biol Sci Med Sci 2020; 74:1716-1724. [PMID: 31107949 DOI: 10.1093/gerona/glz130] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Indexed: 12/31/2022] Open
Abstract
Systemic inflammation is associated with increasing age. Yet, there are limited data about the association between age and systemic inflammation within older adults, and whether older age is also associated with cellular and nuclear signaling markers of inflammation. In community-dwelling older adults (N = 262, 60-88 years), systemic levels of C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptor II; levels of toll-like receptor-4-stimulated monocytic production of interleukin-6 and tumor necrosis factor α; and resting nuclear levels of activated nuclear factor kappa B and signal transducer and activator of transcription (STAT1, STAT3, STAT5) were evaluated. Adjusting for demographic and clinical factors, multivariate linear regression tested the association between age and each inflammatory marker. Age was positively associated with increased levels of interleukin-6 and soluble tumor necrosis factor receptor II (p's < .05) and with increases in STAT1, STAT3, and STAT5 activation (p's < .05). However, no relationship was found between age and C-reactive protein, toll-like receptor-4-stimulated interleukin-6/tumor necrosis factor alpha α production, or nuclear factor kappa B. Within a community-dwelling sample of older adults, older age is associated with increases in STAT activation, along with increases of systemic inflammatory cytokines. In older adults, heterogeneity in age-related increases in inflammatory disease risk may be related to individual variability in inflammation.
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Affiliation(s)
- Dominique Piber
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles.,Department of Psychiatry, Charité-Universitätsmedizin Berlin, Germany
| | - Richard Olmstead
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles
| | - Joshua Hyong-Jin Cho
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles
| | - Tuff Witarama
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles
| | - Christian Perez
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles
| | - Nicholas Dietz
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles
| | - Teresa E Seeman
- Division of Geriatrics, David Geffen School of Medicine, University of California, Los Angeles
| | - Elizabeth C Breen
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles
| | - Steve W Cole
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles
| | - Michael R Irwin
- Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles
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31
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Abstract
The discovery of reciprocal connections between the central nervous system, sleep and the immune system has shown that sleep enhances immune defences and that afferent signals from immune cells promote sleep. One mechanism by which sleep is proposed to provide a survival advantage is in terms of supporting a neurally integrated immune system that might anticipate injury and infectious threats. However, in modern times, chronic social threats can drive the development of sleep disturbances in humans, which can contribute to the dysregulation of inflammatory and antiviral responses. In this Review, I describe our current understanding of the relationship between sleep dynamics and host defence mechanisms, with a focus on cytokine responses, the neuroendocrine and autonomic pathways that connect sleep with the immune system and the role of inflammatory peptides in the homeostatic regulation of sleep. Furthermore, I discuss the therapeutic potential of harnessing these reciprocal mechanisms of sleep-immune regulation to mitigate the risk of inflammatory and infectious diseases.
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32
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Havekes R, Heckman PRA, Wams EJ, Stasiukonyte N, Meerlo P, Eisel ULM. Alzheimer's disease pathogenesis: The role of disturbed sleep in attenuated brain plasticity and neurodegenerative processes. Cell Signal 2019; 64:109420. [PMID: 31536750 DOI: 10.1016/j.cellsig.2019.109420] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Accepted: 09/15/2019] [Indexed: 01/07/2023]
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairments. The classical symptoms of the disease include gradual deterioration of memory and language. Epidemiological studies indicate that around 25-40% of AD patients have sleep-wake cycle disturbances. Importantly, a series of studies suggested that the relationship between AD and sleep disturbance may be complex and bidirectional. Indeed, accumulation of the extracellular neuronal protein amyloid-beta (Aβ) leads to altered sleep-wake behavior in both mice and humans. At the same time, disturbances of the normal sleep-wake cycle may facilitate AD pathogenesis. This paper will review the mechanisms underlying this potential interrelated connection including locus coeruleus damage, reductions in orexin neurotransmission, alterations in melatonin levels, and elevated cytokine levels. In addition, we will also highlight how both the development of AD and sleep disturbances lead to changes in intracellular signaling pathways involved in regulating neuronal plasticity and connectivity, particularly extremes in cofilin phosphorylation. Finally, current pharmacological and nonpharmacological therapeutic approaches will be discussed.
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Affiliation(s)
- Robbert Havekes
- Neurobiology expertise group, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, the Netherlands.
| | - Pim R A Heckman
- Neurobiology expertise group, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, the Netherlands
| | - Emma J Wams
- Neurobiology expertise group, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, the Netherlands
| | - Neringa Stasiukonyte
- Neurobiology expertise group, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, the Netherlands
| | - Peter Meerlo
- Neurobiology expertise group, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, the Netherlands
| | - Ulrich L M Eisel
- Neurobiology expertise group, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, the Netherlands.
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Rice bran extract supplement improves sleep efficiency and sleep onset in adults with sleep disturbance: A randomized, double-blind, placebo-controlled, polysomnographic study. Sci Rep 2019; 9:12339. [PMID: 31451704 PMCID: PMC6710429 DOI: 10.1038/s41598-019-48743-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Accepted: 08/07/2019] [Indexed: 11/30/2022] Open
Abstract
We previously reported that rice bran extract supplement (RBS) administration to mice decreased sleep latency and induced non-rapid eye movement (NREM) sleep via inhibition of the histamine H1 receptor. Based on this, we performed the first clinical trial to investigate whether RBS would be beneficial to subjects with disturbed sleep. We performed a randomized, double‐blinded, placebo‐controlled, 2-week study. Fifty subjects with sleep disturbance were enrolled and received either RBS (1,000 mg/day) or placebo. Polysomnography was performed, and Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale (ESS), and Fatigue Severity Scale were administered at the initiation and termination of the study. Compared with the placebo, RBS led to significant polysomnographic changes, including decreased sleep latency (adjusted, P = 0.047), increased total sleep time (P = 0.019), and improved sleep efficiency (P = 0.010). Additionally, the amount of stage 2 sleep significantly increased in the RBS group. When adjusted for caffeine intake, wakefulness after sleep onset, total wake time, and delta activity tended to decrease in the RBS group. RBS administration decreased ESS scores. There were no reported serious adverse events in both groups. RBS improved sleep in adults with sleep disturbance. Trial registration: WHO ICTRP, KCT0001893.
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Besedovsky L, Lange T, Haack M. The Sleep-Immune Crosstalk in Health and Disease. Physiol Rev 2019; 99:1325-1380. [PMID: 30920354 PMCID: PMC6689741 DOI: 10.1152/physrev.00010.2018] [Citation(s) in RCA: 759] [Impact Index Per Article: 126.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 10/29/2018] [Accepted: 10/29/2018] [Indexed: 02/08/2023] Open
Abstract
Sleep and immunity are bidirectionally linked. Immune system activation alters sleep, and sleep in turn affects the innate and adaptive arm of our body's defense system. Stimulation of the immune system by microbial challenges triggers an inflammatory response, which, depending on its magnitude and time course, can induce an increase in sleep duration and intensity, but also a disruption of sleep. Enhancement of sleep during an infection is assumed to feedback to the immune system to promote host defense. Indeed, sleep affects various immune parameters, is associated with a reduced infection risk, and can improve infection outcome and vaccination responses. The induction of a hormonal constellation that supports immune functions is one likely mechanism underlying the immune-supporting effects of sleep. In the absence of an infectious challenge, sleep appears to promote inflammatory homeostasis through effects on several inflammatory mediators, such as cytokines. This notion is supported by findings that prolonged sleep deficiency (e.g., short sleep duration, sleep disturbance) can lead to chronic, systemic low-grade inflammation and is associated with various diseases that have an inflammatory component, like diabetes, atherosclerosis, and neurodegeneration. Here, we review available data on this regulatory sleep-immune crosstalk, point out methodological challenges, and suggest questions open for future research.
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Affiliation(s)
- Luciana Besedovsky
- Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen , Tübingen , Germany ; Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts ; and Department of Rheumatology and Clinical Immunology, University of Lübeck , Lübeck , Germany
| | - Tanja Lange
- Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen , Tübingen , Germany ; Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts ; and Department of Rheumatology and Clinical Immunology, University of Lübeck , Lübeck , Germany
| | - Monika Haack
- Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen , Tübingen , Germany ; Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts ; and Department of Rheumatology and Clinical Immunology, University of Lübeck , Lübeck , Germany
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Abstract
PURPOSE OF REVIEW Inflammation has emerged as an important biological process in the development of many age-related diseases that occur at different frequencies in men and women. The aim of this review was to examine the current evidence linking stress and sleep with inflammation with a focus on sex differences. RECENT FINDINGS Psychosocial stress that occurs either acutely or chronically is associated with elevated levels of systemic inflammation. While not as robust, insufficient sleep, particularly sleep disturbances, appears to be associated with higher levels of inflammatory activity as well. In several contexts, associations of stress and insufficient sleep with inflammation appear stronger in women than in men. However, this should be interpreted with caution as few studies test for sex differences. Stress and poor sleep often predict elevations in systemic inflammation. While there is some evidence that these associations are stronger in women, findings are largely mixed and more systematic investigations of sex differences in future studies are warranted.
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Mendez N, Torres-Farfan C, Salazar E, Bascur P, Bastidas C, Vergara K, Spichiger C, Halabi D, Vio CP, Richter HG. Fetal Programming of Renal Dysfunction and High Blood Pressure by Chronodisruption. Front Endocrinol (Lausanne) 2019; 10:362. [PMID: 31244775 PMCID: PMC6563621 DOI: 10.3389/fendo.2019.00362] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 05/22/2019] [Indexed: 12/28/2022] Open
Abstract
Adverse prenatal conditions are known to impose significant trade-offs impinging on health and disease balance during adult life. Among several deleterious factors associated with complicated pregnancy, alteration of the gestational photoperiod remains largely unknown. Previously, we reported that prenatal manipulation of the photoperiod has adverse effects on the mother, fetus, and adult offspring; including cardiac hypertrophy. Here, we investigated whether chronic photoperiod shifting (CPS) during gestation may program adult renal function and blood pressure regulation. To this end, pregnant rats were subjected to CPS throughout pregnancy to evaluate the renal effects on the fetus and adult offspring. In the kidney at 18 days of gestation, both clock and clock-controlled gene expression did not display a daily pattern, although there were recurrent weaves of transcriptional activity along the 24 h in the control group. Using DNA microarray, significant differential expression was found for 1,703 transcripts in CPS relative to control fetal kidney (835 up-regulated and 868 down-regulated). Functional genomics assessment revealed alteration of diverse gene networks in the CPS fetal kidney, including regulation of transcription, aldosterone-regulated Na+ reabsorption and connective tissue differentiation. In adult offspring at 90 days of age, circulating proinflammatory cytokines IL-1β and IL-6 were increased under CPS conditions. In these individuals, CPS did not modify kidney clock gene expression but had effects on different genes with specific functions in the nephron. Next, we evaluated several renal markers and the response of blood pressure to 4%NaCl in the diet for 4 weeks (i.e., at 150 days of age). CPS animals displayed elevated systolic blood pressure in basal conditions that remained elevated in response to 4%NaCl, relative to control conditions. At this age, CPS modified the expression of Nhe3, Ncc, Atp1a1, Nr3c1 (glucocorticoid receptor), and Nr3c2 (mineralocorticoid receptor); while Nkcc, Col3A1, and Opn were modified in the CPS 4%+NaCl group. Furthermore, CPS decreased protein expression of Kallikrein and COX-2, both involved in sodium handling. In conclusion, gestational chronodisruption programs kidney dysfunction at different levels, conceivably underlying the prehypertensive phenotype observed in the adult CPS offspring.
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Affiliation(s)
- Natalia Mendez
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology, and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
| | - Claudia Torres-Farfan
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology, and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
- Centro Interdisciplinario de Estudios del Sistema Nervioso, Universidad Austral de Chile, Valdivia, Chile
| | - Esteban Salazar
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology, and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
| | - Pía Bascur
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology, and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
| | - Carla Bastidas
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology, and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
| | - Karina Vergara
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology, and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
| | - Carlos Spichiger
- Faculty of Sciences, Institute of Biochemistry and Microbiology, Universidad Austral de Chile, Valdivia, Chile
| | - Diego Halabi
- Faculty of Medicine, School of Dentistry, Universidad Austral de Chile, Valdivia, Chile
| | - Carlos P. Vio
- Center of Aging and Regeneration CARE, Department of Physiology, Pontificia Universidad Católica de Chile, Valdivia, Chile
- Facultad de Medicina y Ciencia, Universidad San Sebastian, Santiago, Chile
| | - Hans G. Richter
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology, and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
- *Correspondence: Hans G. Richter
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Ding Y, Lin H, Zhou S, Wang K, Li L, Zhang Y, Yao Y, Gao M, Liu X, He N. Stronger Association between Insomnia Symptoms and Shorter Telomere Length in Old HIV-Infected Patients Compared with Uninfected Individuals. Aging Dis 2018; 9:1010-1019. [PMID: 30574414 PMCID: PMC6284770 DOI: 10.14336/ad.2018.0204] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 02/04/2018] [Indexed: 12/15/2022] Open
Abstract
Growing evidence suggests that HIV infection may accelerate biological aging. Insomnia symptoms, particularly in later life, exacerbate cellular aging. We examined the association between insomnia symptoms and leukocyte telomere length (LTL), and further explored how this association was affected by HIV serostatus and age. Data were assessed from 244 HIV-infected individuals ≥40 years and 244 HIV-uninfected individuals who were frequency-matched by age, gender and education level. Insomnia symptoms were assessed by responses to four sleep-related questions covering the past month. We performed multivariable linear regression with logarithmically transformed LTL and reported exponentiated coefficients. HIV-infected individuals had shorter LTL compared to uninfected individuals (geometric mean 0.82 vs 0.89, P=0.052), and this association remained after adjustment for gender, education level, and smoking history (-7.4%, P=0.051) but markedly attenuated after additional adjustment for insomnia and depressive symptoms (-3.7%, P=0.367). Significant interactions between age group (55-82 vs 40-54 years) and insomnia symptoms on LTL were observed in the HIV-infected individuals (-28.4%, P=0.033) but not the uninfected (-17.9%, P=0.250). After stratifying by age group, LTL was independently associated with insomnia symptoms in those 55 years and older among the HIV-infected individuals (-24.5%, P=0.026) but not those 40-54 years old (-9.8%, P=0.428). Our findings suggest that elevated insomnia and depressive symptoms may partly explain the correlation between HIV serostatus and shorter LTL. Significant association between insomnia and shorter LTL observed in elderly HIV-infected but not in uninfected individuals suggest that such adverse effect may begin at an earlier age or is more pronounced in HIV-infected individuals but requires further investigation.
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Affiliation(s)
- Yingying Ding
- 1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,2The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Haijiang Lin
- 3Taizhou City Center for Disease Control and Prevention, Taizhou City, Zhejiang, China
| | - Sujuan Zhou
- 1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,2The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Keran Wang
- 1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,2The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Lingling Li
- 1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,2The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Yucheng Zhang
- 1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,2The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Yuan Yao
- 1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,2The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Meiyang Gao
- 1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,2The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Xing Liu
- 1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,2The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Na He
- 1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,2The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
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Atienza M, Ziontz J, Cantero JL. Low-grade inflammation in the relationship between sleep disruption, dysfunctional adiposity, and cognitive decline in aging. Sleep Med Rev 2018; 42:171-183. [DOI: 10.1016/j.smrv.2018.08.002] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Revised: 07/18/2018] [Accepted: 08/07/2018] [Indexed: 11/27/2022]
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The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis. Sleep Med Rev 2018; 41:255-265. [PMID: 29759891 DOI: 10.1016/j.smrv.2018.03.007] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 02/20/2018] [Accepted: 03/27/2018] [Indexed: 12/29/2022]
Abstract
Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways. In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop. This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders.
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40
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Carrier J, Semba K, Deurveilher S, Drogos L, Cyr-Cronier J, Lord C, Sekerovick Z. Sex differences in age-related changes in the sleep-wake cycle. Front Neuroendocrinol 2017; 47:66-85. [PMID: 28757114 DOI: 10.1016/j.yfrne.2017.07.004] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Revised: 06/09/2017] [Accepted: 07/19/2017] [Indexed: 02/06/2023]
Abstract
Age-related changes in sleep and circadian regulation occur as early as the middle years of life. Research also suggests that sleep and circadian rhythms are regulated differently between women and men. However, does sleep and circadian rhythms regulation age similarly in men and women? In this review, we present the mechanisms underlying age-related differences in sleep and the current state of knowledge on how they interact with sex. We also address how testosterone, estrogens, and progesterone fluctuations across adulthood interact with sleep and circadian regulation. Finally, we will propose research avenues to unravel the mechanisms underlying sex differences in age-related effects on sleep.
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Affiliation(s)
- Julie Carrier
- Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada; Institut Universitaire de Gériatrie de Montréal, Université de Montréal, Montréal, Québec, Canada; Département de psychologie, Université de Montréal, Montréal, Québec, Canada.
| | - Kazue Semba
- Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Psychology & Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Samuel Deurveilher
- Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Lauren Drogos
- Departments of Physiology & Pharmacology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
| | - Jessica Cyr-Cronier
- Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada
| | - Catherine Lord
- Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada
| | - Zoran Sekerovick
- Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada
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The effects of Jiao-Tai-Wan on sleep, inflammation and insulin resistance in obesity-resistant rats with chronic partial sleep deprivation. Altern Ther Health Med 2017; 17:165. [PMID: 28335761 PMCID: PMC5364582 DOI: 10.1186/s12906-017-1648-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2016] [Accepted: 02/23/2017] [Indexed: 01/03/2023]
Abstract
Background Jiao-Tai-Wan (JTW), composed of Rhizome Coptidis and Cortex Cinnamomi, is a classical traditional Chinese prescription for treating insomnia. Several in vivo studies have concluded that JTW could exert its therapeutical effect in insomnia rats. However, the specific mechanism is still unclear. The present study aimed to explore the effect of JTW on sleep in obesity-resistant (OR) rats with chronic partial sleep deprivation (PSD) and to clarify its possible mechanism. Methods JTW was prepared and the main components contained in the granules were identified by 3D-High Performance Liquid Chromatography (3D-HPLC) assay. The Male Sprague-Dawley (SD) rats underwent 4 h PSD by environmental noise and the treatment with low and high doses of JTW orally for 4 weeks, respectively. Then sleep structure was analyzed by electroencephalographic (EEG). Inflammation markers including high-sensitivity C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were examined in the rat plasma. Meanwhile, metabolic parameters as body weight increase rate, fasting plasma glucose (FPG), fasting insulin (FINS) levels and insulin resistance index (HOMA-IR) were measured. The expressions of clock gene cryptochromes (Cry1 and Cry2) and inflammation gene nuclear factor-κB (NF-κB) in peripheral blood monocyte cells (PBMC) were also determined. Results The result showed that the administration of JTW significantly increased total sleep time and total slow wave sleep (SWS) time in OR rats with PSD. Furthermore, the treatment with JTW reversed the increase in the markers of systemic inflammation and insulin resistance caused by sleep loss. These changes were also associated with the up-regulation of Cry1 mRNA and Cry 2 mRNA and the down-regulation of NF-κB mRNA expression in PBMC. Conclusions This study suggests that JTW has the beneficial effects of improving sleep, inflammation and insulin sensitivity. The mechanism appears to be related to the modulation of circadian clock and inflammation genes expressions in PBMC.
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Irwin MR, Opp MR. Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity. Neuropsychopharmacology 2017; 42:129-155. [PMID: 27510422 PMCID: PMC5143488 DOI: 10.1038/npp.2016.148] [Citation(s) in RCA: 298] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Revised: 07/29/2016] [Accepted: 08/02/2016] [Indexed: 12/11/2022]
Abstract
Sleep disturbances including insomnia independently contribute to risk of inflammatory disorders and major depressive disorder. This review and overview provides an integrated understanding of the reciprocal relationships between sleep and the innate immune system and considers the role of sleep in the nocturnal regulation of the inflammatory biology dynamics; the impact of insomnia complaints, extremes of sleep duration, and experimental sleep deprivation on genomic, cellular, and systemic markers of inflammation; and the influence of sleep complaints and insomnia on inflammaging and molecular processes of cellular aging. Clinical implications of this research include discussion of the contribution of sleep disturbance to depression and especially inflammation-related depressive symptoms. Reciprocal action of inflammatory mediators on the homeostatic regulation of sleep continuity and sleep macrostructure, and the potential of interventions that target insomnia to reverse inflammation, are also reviewed. Together, interactions between sleep and inflammatory biology mechanisms underscore the implications of sleep disturbance for inflammatory disease risk, and provide a map to guide the development of treatments that modulate inflammation, improve sleep, and promote sleep health.
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Affiliation(s)
- Michael R Irwin
- Department of Psychiatry and Biobehavioral Sciences, Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience Director and Mindful Awareness Research Center, University of California, Los Angeles, CA, USA
| | - Mark R Opp
- Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA
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Daulatzai MA. Fundamental role of pan-inflammation and oxidative-nitrosative pathways in neuropathogenesis of Alzheimer's disease in focal cerebral ischemic rats. AMERICAN JOURNAL OF NEURODEGENERATIVE DISEASE 2016; 5:102-30. [PMID: 27335702 PMCID: PMC4913220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Accepted: 02/09/2016] [Indexed: 06/06/2023]
Abstract
Alzheimer's disease (AD) is a chronic progressive neurodegenerative condition of the brain, and it is the most common cause of dementia. Several neurobiological etiologies of AD are described in the literature. These include vascular, infectious, toxic, nutritional, metabolic, and inflammatory. However, these heterogeneous etiologies have a common denominator - viz. Inflammation and oxidative stress. Lipopolysaccharide (LPS) elevates the synthesis of proinflammatory cytokines and chemokines; chronically, together they trigger various pathological responses in the periphery and the CNS including dysfunctional memory consolidation and memory decline. Aging - the main risk factor for AD is inherently associated with inflammation. There are several age-related comorbidities that are also associated with inflammation and oxidative stress. Such co-prevailing aggravating factors, therefore, persist against a background of underlying aging-related pathology. They may converge, and their synergistic propagation may modify the disease course. A critical balance exists between homeostasis/repair and inflammatory factors; chronic, unrelenting inflammatory milieu succeeds in promoting a neuroinflammatory and neurodegenerative outcome. Extensive evidence is available that CNS inflammation is associated with neurodegeneration. LPS, proinflammatory cytokines, several mediators secreted by microglia, and oxidative-nitrosative stress in concert play a pivotal role in triggering neuroinflammatory processes and neurodegeneration. The persistent uncontrolled activity of the above factors can potentiate cognitive decline in tandem enhancing vulnerability to AD. Despite significant progress during the past twenty years, the prevention and treatment of AD have been tantalizingly elusive. Current studies strongly suggest that amelioration/prevention of the deleterious effects of inflammation may prove beneficial in preventing AD onset and retarding cognitive dysfunction in aging and AD. A concerted multi-focal therapeutic effort around the inflammation-oxidative-nitrosative stress paradigm may be crucial in preventing and treating AD. This paper informs on such relevant polypharmacy approach.
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Affiliation(s)
- Mak Adam Daulatzai
- Sleep Disorders Group, EEE/Melbourne School of Engineering, The University of Melbourne Parkville, Victoria 3010, Australia
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44
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Daulatzai MA. Fundamental role of pan-inflammation and oxidative-nitrosative pathways in neuropathogenesis of Alzheimer's disease. AMERICAN JOURNAL OF NEURODEGENERATIVE DISEASE 2016; 5:1-28. [PMID: 27073740 PMCID: PMC4788729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Accepted: 02/09/2016] [Indexed: 06/05/2023]
Abstract
Alzheimer's disease (AD) is a chronic progressive neurodegenerative condition of the brain, and it is the most common cause of dementia. Several neurobiological etiologies of AD are described in the literature. These include vascular, infectious, toxic, nutritional, metabolic, and inflammatory. However, these heterogeneous etiologies have a common denominator - viz. Inflammation and oxidative stress. Lipopolysaccharide (LPS) elevates the synthesis of proinflammatory cytokines and chemokines; chronically, together they trigger various pathological responses in the periphery and the CNS including dysfunctional memory consolidation and memory decline. Aging - the main risk factor for AD is inherently associated with inflammation. There are several age-related comorbidities that are also associated with inflammation and oxidative stress. Such co-prevailing aggravating factors, therefore, persist against a background of underlying aging-related pathology. They may converge, and their synergistic propagation may modify the disease course. A critical balance exists between homeostasis/repair and inflammatory factors; chronic, unrelenting inflammatory milieu succeeds in promoting a neuroinflammatory and neurodegenerative outcome. Extensive evidence is available that CNS inflammation is associated with neurodegeneration. LPS, proinflammatory cytokines, several mediators secreted by microglia, and oxidative-nitrosative stress in concert play a pivotal role in triggering neuroinflammatory processes and neurodegeneration. The persistent uncontrolled activity of the above factors can potentiate cognitive decline in tandem enhancing vulnerability to AD. Despite significant progress during the past twenty years, the prevention and treatment of AD have been tantalizingly elusive. Current studies strongly suggest that amelioration/prevention of the deleterious effects of inflammation may prove beneficial in preventing AD onset and retarding cognitive dysfunction in aging and AD. A concerted multi-focal therapeutic effort around the inflammation-oxidative-nitrosative stress paradigm may be crucial in preventing and treating AD. This paper informs on such relevant polypharmacy approach.
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Affiliation(s)
- Mak Adam Daulatzai
- Sleep Disorders Group, EEE/Melbourne School of Engineering, The University of Melbourne Parkville, Victoria 3010, Australia
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Carroll JE, Cole SW, Seeman TE, Breen EC, Witarama T, Arevalo JM, Ma J, Irwin MR. Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans. Brain Behav Immun 2016; 51:223-229. [PMID: 26336034 PMCID: PMC4679552 DOI: 10.1016/j.bbi.2015.08.024] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 07/28/2015] [Accepted: 08/30/2015] [Indexed: 12/11/2022] Open
Abstract
Age-related disease risk has been linked to short sleep duration and sleep disturbances; however, the specific molecular pathways linking sleep loss with diseases of aging are poorly defined. Key cellular events seen with aging, which are thought to contribute to disease, may be particularly sensitive to sleep loss. We tested whether one night of partial sleep deprivation (PSD) would increase leukocyte gene expression indicative of DNA damage responses (DDR), the senescence-associated secretory phenotype (SASP), and senescence indicator p16(INK4a) in older adult humans, who are at increased risk for cellular senescence. Community-dwelling older adults aged 61-86years (n=29; 48% male) underwent an experimental partial sleep deprivation (PSD) protocol over 4 nights, including adaptation, an uninterrupted night of sleep, partial sleep deprivation (sleep restricted 3-7AM), and a subsequent full night of sleep. Blood samples were obtained each morning to assess peripheral blood mononuclear cell (PBMC) gene expression using Illumina HT-12 arrays. Analyses of microarray results revealed that SASP (p<.05) and DDR (p=.08) gene expression were elevated from baseline to PSD nights. Gene expression changes were also observed from baseline to PSD in NFKB2, NBS1 and CHK2 (all p's<.05). The senescence marker p16(INK4a) (CDKN2A) was increased 1day after PSD compared to baseline (p<.01), however confirmatory RT-PCR did not replicate this finding. One night of partial sleep deprivation activates PBMC gene expression patterns consistent with biological aging in this older adult sample. PSD enhanced the SASP and increased the accumulation of damage that initiates cell cycle arrest and promotes cellular senescence. These findings causally link sleep deprivation to the molecular processes associated with biological aging.
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Affiliation(s)
- Judith E. Carroll
- University of California, Los Angeles, Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior
| | - Steven W. Cole
- University of California, Los Angeles, Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior,Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine
| | - Teresa E. Seeman
- University of California, Los Angeles, Department of Geriatrics, David Geffen School of Medicine
| | - Elizabeth C. Breen
- University of California, Los Angeles, Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior
| | - Tuff Witarama
- University of California, Los Angeles, Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior
| | - Jesusa M.G. Arevalo
- Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine
| | - Jeffrey Ma
- Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine
| | - Michael R. Irwin
- University of California, Los Angeles, Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior
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