Elucidating the Interplay of Hypoxia-Inducible Factor and Circadian Clock Signaling in Obstructive Sleep Apnea Patients

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 971 - 971

Published: Jan. 24, 2025

Background: Hypoxia-inducible factor 1 (HIF-1) affects the circadian clock in obstructive sleep apnea (OSA) and may have a bidirectional relationship with mechanisms. This study examined link between HIF-1 OSA patients versus controls. Methods: 70 participants underwent polysomnography (PSG), were assigned into (apnea–hypopnea index (AHI) ≥ 5, n = 54) or control (AHI < 16) groups. BMAL1 (brain muscle ARNT like 1), CLOCK (circadian locomotor output cycles kaput), PER1 (period CRY1 (cryptochrome HIF-1α, HIF-1β gene expressions protein levels measured evening morning samples, collected before after PSG. Results: The group was characterized by increased CLOCK, CRY1, HIF-1a levels, both (all p 0.05), decreased expression of (p 0.02). Associations almost all subunits observed at time points apart from association HIF-1α (R 0.050, 0.73). In controls, only correlation 0.588, 0.02) found. Conclusions: pathway, PER1, patients. interplay these systems involve complex posttranscriptional posttranslational

Language: Английский

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Sleep and Male (In)Fertility: A Comprehensive Overview

Sleep Medicine Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102080 - 102080

Published: March 1, 2025

Infertility affects millions of couples globally, with male factors contributing up to 50 % cases. Despite the existing Assisted Reproduction Technologies (ART), decreased sperm quality and infertility persist. Evidence suggests that sleep is crucial for normal reproductive function, noticeable increase in rates aligns growing prevalence deprivation, suggesting a connection between both conditions. This literature review explores possible links disturbances, special emphasis on insomnia, most prevalent disorder, health. It delves into latest findings regarding such as quality, hormone levels, overall function from studies mammals, rodents humans. Through concise synthesis these findings, we unveil potential mechanisms provide insights clinicians researchers field

Language: Английский

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Correlation of the expression of circadian-clock genes with the severity of obstructive sleep apnea in patients

Chronobiology International, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: March 20, 2025

This study investigates the connection of Obstructive Sleep Apnea (OSA) with expression and daily oscillation patterns core circadian clock genes related genes. OSA, a sleep disorder characterized by repetitive airway occlusion leading to nocturnal arousals, fragmentation, intermittent hypoxemia (IH), shares dysfunction as an overlapping phenotype The research involved 40 subjects (30 OSA patients 10 normal controls), categorized into four groups based on Polysomnography (PSG) results: normal, mild, moderate, severe. Peripheral blood samples were collected twice from each participant in evening before morning after PSG examination. Using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR), measured levels target leukocytes. Results revealed changes diurnal several (PER1, PER3, CRY1, BMAL1, CLOCK, HIF-1α, IL-1β, TNFα) compared controls. While PER2, CRY2, NPAS2 did not show patterns, their was significantly elevated severe OSA. Notably, TNFα increased severity, consistent roles IH inflammation clinical indicators These findings only demonstrate that clock-related gene fluctuates but also provide potential molecular markers for early diagnosis personalized treatment. By identifying biomarkers parallel this innovative paves way future applications field.

Language: Английский

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The dark side of apnea: altered 24-hour melatonin secretion in obstructive sleep apnea (OSAS) is disease severity dependent

Sleep And Breathing, Journal Year: 2024, Volume and Issue: 28(4), P. 1751 - 1759

Published: May 27, 2024

Abstract Purpose Melatonin aids in the synchronization of circadian rhythm to external environment. Few studies have tried elucidate relationship between melatonin and obstructive sleep apnea syndrome (OSAS). These often include few patients, do not differentiate OSAS severity and/or analyse a 24-h profile. This study set out investigate disease dependent differences salivary secretion patients compared reference population retrospective design. Methods profiles 169 were analysed (55 light, 66 moderate, 48 severe) as well 91 patients. Several aspects curve stratified according severity. Parameters included: dim light onset (DLMO), time returning below DLMO (DLMOoff), peak concentration time, total exposure. Results Significant effects corrected for confounding by age sex using linear regression. Our analysis shows that, manner, significantly lower curve, concentration, exposure smaller proportion reach DLMO. The production resistant sex. Conclusion describes clear abnormalities independent age. Future research should indicate whether oral supplementation has beneficial with attenuated endogenous production.

Language: Английский

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Circadian Rhythms are Disrupted in Patients and Preclinical Models of Machado-Joseph Disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Abstract Machado-Joseph disease (MJD) is caused by an abnormal CAG repeat expansion in the ATXN3 gene, leading to expression of a mutant ataxin-3 (mutATXN3) protein. MJD patients exhibit wide range clinical symptoms, including motor incoordination. Emerging evidence highlights circadian rhythm disruptions as early indicators and potential risk factors for progression neurodegenerative conditions. Circadian rhythms are regulated internal clocks, with suprachiasmatic nucleus (SCN) acting master pacemaker synchronize timing across body’s behavioural physiological functions. While sleep disturbances have been observed MJD, role clock regulation its pathophysiology remains largely unexplored spinocerebellar ataxias. This study aimed investigate rhythms, characterize associated disruptions, uncover mechanisms underlying dysregulation preclinical models MJD. activity was assessed over two weeks using actigraphy, while YAC-MJD transgenic mouse model, were examined through: (a) wheel-running experiments; (b) telemetry-based monitoring core body temperature; (c) immunohistochemical analysis neuropeptides arginine vasopressin (AVP) vasoactive intestinal polypeptide (VIP) SCN paraventricular (PVN); (d) RT-qPCR evaluation gene cerebellum. The impact mutATXN3 on further investigated Bmal1 / Per2- luciferase reporters. exhibited progressive decline robustness demonstrated negative correlations between function index, rest-activity fragmentation, efficiency scales. mice reduced levels, increased required three additional days re-entrain after jet lag protocol, compared controls. Disrupted temperature observed, phase advance elevated (∼1 °C) at onset active period. Furthermore, showed levels VIP AVP PVN, decreased Lastly, we found new mechanistic that WT activates promoters Per2 , whereas loses capacity drive upon polyglutamine expansion. Overall, our findings indicate central dysfunction impaired rhythms. provides first robust paving way identification biomarkers development novel circadian-based interventions tackle possibly other Graphical abstract

Language: Английский

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Obstructive sleep apnea syndrome, orexin, and sleep–wake cycle: The link with the neurodegeneration

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 141 - 160

Published: Jan. 1, 2025

Language: Английский

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Circadian biology in obstructive sleep apnea associated cardiovascular disease

Journal of Molecular and Cellular Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Assessment of continuous positive airway pressure effect on the circadian clock signaling pathway in obstructive sleep apnea patients

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 2, 2025

Obstructive sleep apnea (OSA) is associated with circadian rhythm dysregulation plausibly through affecting clock genes. The study's purpose was to investigate the effect of one-night continuous positive airway pressure treatment (CPAP treatment) on genes: BMAL1, CLOCK, CRY1, and PER1 at mRNA protein levels. study included 30 OSA patients, who underwent diagnostic polysomnography (PSG) next a effective CPAP PSG monitoring (CPAP). blood collected in evening before morning after CPAP. Protein levels expression were measured using ELISA qRT-PCR, respectively. increase observed compared (p = 0.005); additionally, level decreased 0.035). In CLOCK significant changes observed: an 0.049), 0.006), difference between vs. 0.012). Obtained results suggest that even short-term might reverse signaling pathway disruption OSA.

Language: Английский

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Circadian Regulation in Diurnal Mammals: Neural Mechanisms and Implications in Translational Research

Biology, Journal Year: 2024, Volume and Issue: 13(12), P. 958 - 958

Published: Nov. 22, 2024

Diurnal and nocturnal mammals have evolved unique behavioral physiological adaptations to optimize survival for their day- or night-active lifestyle. The mechanisms underlying the opposite activity patterns are not fully understood but likely involve interplay between circadian time-keeping system various arousal- sleep-promoting factors, e.g., light melatonin. Although systems two chronotypes share considerable similarities, phase relationships principal subordinate oscillators chronotype-specific. While promotes arousal wakefulness in diurnal species like us, it induces sleep ones. Similarly, melatonin, hormone of darkness, is commonly used as a hypnotic humans secreted active animals. Thus, difference more complex than simple reversal, neurological processes during day equivalent that ones at night. Such chronotype differences could present significant translational gap when applying research findings obtained from rodents humans. potential advantages models being discussed few sleep-related conditions including familial natural short (FNSS), obstructive apnea (OSA), Smith-Magenis syndrome (SMS). Considering chronotype, model will be adequate revealing physiology physiopathology pertaining human health disease, especially which rhythm disruption, altered photic response, melatonin secretion involved. We hope recent advances gene editing promote greater utility basic research.

Language: Английский

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Changes in cortisol levels by continuous positive airway pressure in patients with obstructive sleep apnoea: Meta‐analysis of 637 individuals

Clinical Endocrinology, Journal Year: 2021, Volume and Issue: 95(6), P. 909 - 917

Published: July 29, 2021

Obesity, obstructive sleep apnoea (OSA) and hypertension frequently coexist are associated with elevated cortisol levels. Identification treatment of such patients is important when investigating for suspected Cushing's syndrome hypertension. Studies the impact continuous positive airway pressure (CPAP) on blood limited by small sample size show conflicting findings. We conducted a meta-analysis to document changes in levels response CPAP OSA.Meta-analysis was using RevMan (v5.3) expressed standardized mean difference (SMD) catecholamines systolic (SBP) diastolic (DBP). The quality studies evaluated standard tools assessing risk bias.A total 22 met our search criteria; they consisted 16 prospective cohort (PCS) that recruited 385 participants six randomized control trials (RCT) totalling 252 participants. range age 41-62 years BMI 27.2-35.1 kg/m2 . reduced plasma PCS: SMD = -0.28 [95% confidence interval (95% CI) -0.45 -0.12], I2 0%, p .79 RCT: -0.39 CI -0.75 -0.03), 28.3%, .25. SBP 5.4 mmHg 1.7-9.1) DBP 3.3 1.0-5.7). Interstudy heterogeneity low all studies. Bias most RCT arose from lack blinding personnel.CPAP individuals OSA reduces pressure.

Language: Английский

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