Obstructive Sleep Apnea and Serotoninergic Signalling Pathway: Pathomechanism and Therapeutic Potential.

Obstructive Sleep Apnea (OSA) is a disorder characterized by repeated upper airway collapse during sleep, leading to apneas and/or hypopneas, with associated symptoms like intermittent hypoxia and sleep fragmentation. One of the agents contributing to OSA occurrence and development seems to be serotonin (5-HT). Currently, the research focuses on establishing and interlinking OSA pathogenesis and the severity of the disease on the molecular neurotransmitter omnipresent in the human body-serotonin, its pathway, products, receptors, drugs affecting the levels of serotonin, or genetic predisposition. The 5-HT system is associated with numerous physiological processes such as digestion, circulation, sleep, respiration, and muscle tone-all of which are considered factors promoting and influencing the course of OSA because of correlations with comorbid conditions. Comorbidities include obesity, physiological and behavioral disorders as well as cardiovascular diseases. Additionally, both serotonin imbalance and OSA are connected with psychiatric comorbidities, such as depression, anxiety, or cognitive dysfunction. Pharmacological agents that target 5-HT receptors have shown varying degrees of efficacy in reducing the Apnea-Hypopnea Index and improving OSA symptoms. The potential role of the 5-HT signaling pathway in modulating OSA provides a promising avenue for new therapeutic interventions that could accompany the primary treatment of OSA-continuous positive airway pressure. Thus, this review aims to elucidate the complex role of 5-HT and its regulatory mechanisms in OSA pathophysiology, evaluating its potential as a therapeutic target. We also summarize the relationship between 5-HT signaling and various physiological functions, as well as its correlations with comorbid conditions.

Investigating the Link between Circadian Clock Gene Expressions, Chronotype, Insomnia, and Daytime Sleepiness in Patients with Obstructive Sleep Apnea.

INTRODUCTION: This study aimed to investigate the relationship between obstructive sleep apnea (OSA), circadian rhythms, and individual sleep-wake preferences, as measured by chronotype, and to assess the association between circadian clock gene expression and subjective sleep-related variables. METHODS: A total of 184 individuals were recruited, underwent polysomnography (PSG), and completed questionnaires including a chronotype questionnaire (CQ), insomnia severity index (ISI), and Epworth sleepiness scale (ESS). Blood samples were collected in the evening before and morning after PSG. Gene expression analysis included BMAL1, CLOCK, PER1, CRY1, NPAS2, and NR1D1. RESULTS: In the OSA group, the subjective amplitude (AM score of CQ) positively correlated with all circadian clock genes in the morning (R ≥ 0.230 and p < 0.05 for each one), while the morningness-eveningness (ME score of CQ) was only associated with the evening BMAL1 level (R = 0.192; p = 0.044). In healthy controls, insomnia severity correlated with evening expression of BMAL1, PER1, and CRY1. CONCLUSIONS: The findings highlight the complex interplay between OSA, circadian rhythms, and sleep-related variables, suggesting potential determinants of morning chronotype in OSA and implicating disrupted circadian clock function in subjective feelings of energy throughout the day. Further research is warranted to elucidate underlying mechanisms and guide personalized management strategies.

The Complex Relationship between Neuromodulators, Circadian Rhythms, and Insomnia in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has been linked to disruptions in circadian rhythm and neurotrophin (NFT) signaling. This study explored the link between neuromodulators, chronotype, and insomnia in OSA. The participants (n = 166) underwent polysomnography (PSG) before being categorized into either the control or the OSA group. The following questionnaires were completed: Insomnia Severity Index (ISI), Epworth Sleepiness Scale, Chronotype Questionnaire (morningness-eveningness (ME), and subjective amplitude (AM). Blood samples were collected post-PSG for protein level assessment using ELISA kits for brain-derived neurotrophic factor (BDNF), proBDNF, glial-cell-line-derived neurotrophic factor, NFT3, and NFT4. Gene expression was analyzed utilizing qRT-PCR. No significant differences were found in neuromodulator levels between OSA patients and controls. The controls with insomnia exhibited elevated neuromodulator gene expression (p < 0.05). In the non-insomnia individuals, BDNF and NTF3 expression was increased in the OSA group compared to controls (p = 0.007 for both); there were no significant differences between the insomnia groups. The ISI scores positively correlated with all gene expressions in both groups, except for NTF4 in OSA (R = 0.127, p = 0.172). AM and ME were predicting factors for the ISI score and clinically significant insomnia (p < 0.05 for both groups). Compromised compensatory mechanisms in OSA may exacerbate insomnia. The correlation between chronotype and NFT expression highlights the role of circadian misalignments in sleep disruptions.

Neurotrophins in the Neuropathophysiology, Course, and Complications of Obstructive Sleep Apnea-A Narrative Review.

Obstructive sleep apnea (OSA) is a disorder characterized by chronic intermittent hypoxia and sleep fragmentation due to recurring airway collapse during sleep. It is highly prevalent in modern societies, and due to its pleiotropic influence on the organism and numerous sequelae, it burdens patients and physicians. Neurotrophins (NTs), proteins that modulate the functioning and development of the central nervous system, such as brain-derived neurotrophic factor (BDNF), have been associated with OSA, primarily due to their probable involvement in offsetting the decline in cognitive functions which accompanies OSA. However, NTs influence multiple aspects of biological functioning, such as immunity. Thus, extensive evaluation of their role in OSA might enlighten the mechanism behind some of its elusive features, such as the increased risk of developing an immune-mediated disease or the association of OSA with cardiovascular diseases. In this review, we examine the interactions between NTs and OSA and discuss their contribution to OSA pathophysiology, complications, as well as comorbidities.

Evaluation of the Continuous Positive Airway Pressure Effect on Neurotrophins' Gene Expression and Protein Levels.

Neurotrophins (NT) might be associated with the pathophysiology of obstructive sleep apnea (OSA) due to concurrent intermittent hypoxia and sleep fragmentation. Such a relationship could have implications for the health and overall well-being of patients; however, the literature on this subject is sparse. This study investigated the alterations in the serum protein concentration and the mRNA expression of the brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NTF3), and neurotrophin-4 (NTF4) proteins following a single night of continuous positive airway pressure (CPAP) therapy. This study group consisted of 30 patients with OSA. Venous blood was collected twice after a diagnostic polysomnography (PSG) and PSG with CPAP treatment. Gene expression was assessed with a quantitative real-time polymerase chain reaction. An enzyme-linked immunosorbent assay was used to determine the protein concentrations. After CPAP treatment, BDNF, proBDNF, GDNF, and NTF4 protein levels decreased (p = 0.002, p = 0.003, p = 0.047, and p = 0.009, respectively), while NTF3 increased (p = 0.001). Sleep latency was correlated with ΔPSG + CPAP/PSG gene expression for BDNF (R = 0.387, p = 0.038), NTF3 (R = 0.440, p = 0.019), and NTF4 (R = 0.424, p = 0.025). OSA severity parameters were not associated with protein levels or gene expressions. CPAP therapy could have an impact on the posttranscriptional stages of NT synthesis. The expression of different NTs appears to be connected with sleep architecture but not with OSA severity.

Inflammasome signalling pathway in the regulation of inflammation - its involvement in the development and exacerbation of asthma and chronic obstructive pulmonary disease.

Inflammasomes are multiprotein oligomers, whose main function is the recruitment and activation of caspase-1, which cleaves the precursor forms of interleukin (IL)-1ß and IL-18, generating biologically active cytokines. Activation of inflammasome is an essential component of the innate immune response, and according to recent reports it is involved in epithelial homeostasis and type 2 T helper cell (Th2) differentiation. In recent years, the contribution of inflammasome dependent signalling pathways to the development of inflammatory diseases became a topic of multiple research studies. Asthma and chronic obstructive pulmonary disease (COPD) are the most prevalent obstructive lung diseases. Recent studies have focused on inflammatory aspects of asthma and COPD development, demonstrating the key role of inflammasome-dependent processes. Factors responsible for activation of inflammasome complex are similar in both asthma and COPD and include bacteria, viruses, cigarette smoke, and particulate matter. Some recent studies have revealed that NLRP3 inflammasome plays a crucial role, particularly in the development of acute exacerbations of COPD (AECOPD). Activation of NLRP3 inflammasome has been linked with neutrophilic severe steroid-resistant asthma. Although most of the studies on inflammasomes in asthma and COPD focused on the NLRP3 inflammasome, there are scarce scientific reports linking other inflammasomes such as AIM2 and NLRP1 with obstructive lung diseases. In this mini review we focus on the role of molecular pathways associated with inflammasome in the most prevalent lung diseases such as asthma and COPD. Furthermore, we will try to answer the question of whether inhibition of inflammasome can occur as a modern therapy in these diseases.

Evaluation of HIF-1 Involvement in the BDNF and ProBDNF Signaling Pathways among Obstructive Sleep Apnea Patients.

Obstructive Sleep Apnea (OSA) is a chronic condition characterized by intermittent hypoxia associated with multiple comorbidities, including psychiatric disorders, such as depression, insomnia, and cognitive impairment. The brain-derived neurotrophic factor (BDNF) and proBDNF singling pathways have been shown to be involved in this group of diseases. Furthermore, their expression might be affected by hypoxia-inducible factor 1 (HIF-1), which is an oxygen sensitive transcription factor due to its alpha subunit. Therefore, this study aimed to evaluate the association between HIF-1α, BDNF, and proBDNF protein levels among OSA patients. This study included 40 individuals who underwent polysomnography (PSG) and were divided into the OSA group (n = 20; AHI ≥ 30) and healthy control (n = 20; AHI < 5) based on the apnea−hypopnea index (AHI). All participants had their peripheral blood collected in the evening before and the morning after the PSG. BDNF, proBDNF, and HIF-1α protein concertation measurements were performed using ELISA. No differences were found in BDNF, proBDNF, and HIF-1α protein levels between OSA and the control group, both in the evening and in the morning. In the OSA group, i.e., the linear regression model, the morning BDNF protein level was predicted by age (ß = −0.389, p = 0.023) and the mean SpO2 of desaturations during sleep (ß = −0.577, p = 0.002). This model accounted for 63.3% of the variability in the morning BDNF protein level (F = 14.639, p < 0.001). The morning proBDNF protein level was predicted by age (ß = −0.395, p = 0.033) and HIF-1α morning protein level (ß = −3.192, p = 0.005). This model accounted for 52.4% of the variability in the morning BDNF protein level (F = 9.355, p = 0.002). The obtained results suggest that the HIF-1 transcription factor might be involved in the pathway activated by proBDNF, which may have protective properties from hypoxia in OSA patients.

Disruption of Circadian Rhythm Genes in Obstructive Sleep Apnea Patients-Possible Mechanisms Involved and Clinical Implication.

Obstructive sleep apnea (OSA) is a chronic condition characterized by recurrent pauses in breathing caused by the collapse of the upper airways, which results in intermittent hypoxia and arousals during the night. The disorder is associated with a vast number of comorbidities affecting different systems, including cardiovascular, metabolic, psychiatric, and neurological complications. Due to abnormal sleep architecture, OSA patients are at high risk of circadian clock disruption, as has been reported in several recent studies. The circadian clock affects almost all daily behavioral patterns, as well as a plethora of physiological processes, and might be one of the key factors contributing to OSA complications. An intricate interaction between the circadian clock and hypoxia may further affect these processes, which has a strong foundation on the molecular level. Recent studies revealed an interaction between hypoxia-inducible factor 1 (HIF-1), a key regulator of oxygen metabolism, and elements of circadian clocks. This relationship has a strong base in the structure of involved elements, as HIF-1 as well as PER, CLOCK, and BMAL, belong to the same Per-Arnt-Sim domain family. Therefore, this review summarizes the available knowledge on the molecular mechanism of circadian clock disruption and its influence on the development and progression of OSA comorbidities.

The Role of Inflammation, Hypoxia, and Opioid Receptor Expression in Pain Modulation in Patients Suffering from Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a relatively common disease in the general population. Besides its interaction with many comorbidities, it can also interact with potentially painful conditions and modulate its course. The association between OSA and pain modulation has recently been a topic of concern for many scientists. The mechanism underlying OSA-related pain connection has been linked with different pathophysiological changes in OSA and various pain mechanisms. Furthermore, it may cause both chronic and acute pain aggravation as well as potentially influencing the antinociceptive mechanism. Characteristic changes in OSA such as nocturnal hypoxemia, sleep fragmentation, and systemic inflammation are considered to have a curtailing impact on pain perception. Hypoxemia in OSA has been proven to have a significant impact on increased expression of proinflammatory cytokines influencing the hyperalgesic priming of nociceptors. Moreover, hypoxia markers by themselves are hypothesized to modulate intracellular signal transduction in neurons and have an impact on nociceptive sensitization. Pain management in patients with OSA may create problems arousing from alterations in neuropeptide systems and overexpression of opioid receptors in hypoxia conditions, leading to intensification of side effects, e.g., respiratory depression and increased opioid sensitivity for analgesic effects. In this paper, we summarize the current knowledge regarding pain and pain treatment in OSA with a focus on molecular mechanisms leading to nociceptive modulation.

The predictive value of BOAH scale for screening obstructive sleep apnea in patients at a sleep clinic in Scotland.

OBJECTIVES: The study aimed to evaluate the diagnostic value of an original questionnaire for obstructive sleep apnea (OSA), the BOAH scale, and its ability to prioritize patients at high risk for OSA for polysomnography (PSG) examination. METHODS: The analysis included 273 patients referred to the Department of Sleep Medicine of the Royal Infirmary, Edinburgh, Scotland. The BOAH scale is comprised of 5 parameters: BMI (≥ 30 kg/m2 gives 1 point, ≥ 35 kg/m2 2 points), presence of witnessed apneas during sleep (1 point), patient age ≥ 50 years (1 point), and history of hypertension (1 point). Patients were divided into three study groups depending on OSA severity defined by the apnea-hypopnea index (AHI): at least mild (AHI ≥ 5), at least moderate (AHI ≥ 15), and severe (AHI ≥ 30) OSA based on polysomnography examination. RESULTS: In the group of patients with severe OSA, the best BOAH cutoff point was 4 points based upon the Youden index. With 4 points, the area under the receiver operating characteristic (ROC) curve was 0.778 (95% CI 0.721-0.834). Sensitivity and specificity were 57% and 89%, respectively, yielding a positive and negative predictive value of 75% and 78%, respectively, for diagnosis of severe OSAS in a patient sample with a pre-test probability for severe OSA at 37%. CONCLUSIONS: The BOAH scale in this group of Scottish patients performed comparably to other available questionnaires and scales while being shorter and simpler. The findings suggest that the BOAH scale should be considered as a useful instrument in OSA diagnosis and prioritization of high-risk patients for PSG examination.

Obstructive Sleep Apnea as an Acceleration Trigger of Cellular Senescence Processes through Telomere Shortening.

Obstructive sleep apnea (OSA) is chronic disorder which is characterized by recurrent pauses of breathing during sleep which leads to hypoxia and its two main pathological sequelae: oxidative stress and chronic inflammation. Both are also associated with cellular senescence. As OSA patients present with higher prevalence of age-related disorders, such as atrial hypertension or diabetes mellitus type 2, a relationship between OSA and accelerated aging is observable. Furthermore, it has been established that these OSA are associated with telomere shortening. This process in OSA is likely caused by increased oxidative DNA damage due to increased reactive oxygen species levels, DNA repair disruptions, hypoxia, chronic inflammation, and circadian clock disturbances. The aim of the review is to summarize study outcomes on changes in leukocyte telomere length (LTL) in OSA patients and describe possible molecular mechanisms which connect cellular senescence and the pathophysiology of OSA. The majority of OSA patients are characterized by LTL attrition due to oxidative stress, hypoxia and inflammation, which make a kind of positive feedback loop, and circadian clock disturbance.

Can spectral power predict subjective sleep quality in healthy individuals?

The aim of this study was to assess the relationship between electroencephalogram (EEG) power spectral density and subjective sleep quality in healthy individuals. The sample was selected from the archival database of the Sleep Center at the Department for Psychiatry and Psychotherapy, Medical Center - University of Freiburg, and consisted of 206 healthy adults aged 19-73 years (85 male, 121 female) who underwent a polysomnographic examination for two consecutive nights. A multivariate analysis of variance (MANOVA) with spectral power variables of different frequency bands as dependent variables and subjective sleep quality, night number, age and gender as independent variables was statistically significant for subjective sleep quality, age and gender, but not for night number. In subsequent separate ANOVAs, higher subjective sleep quality was significantly related to decreased non-rapid eye movement (NREM) stage 2 sigma 2 and rapid eye movement (REM) delta 1; however, the relation between REM delta 1 and sleep quality did not remain significant when REM duration was accounted for. The effect sizes of the correlations between sleep quality and spectral power were small (r = -0.1). In contrast to common assumptions, the amount of variance in subjective sleep quality that can be explained through EEG power spectral density variables is small. This finding indicates that subjective and objective sleep are different constructs, the interrelations of which are not yet well understood.

Obstructive sleep apnea syndrome and hypothyroidism - merely concurrence or causal association?

The prevalence of obstructive sleep apnea-hypopnea syndrome (OSAHS) ranges from 4 to 7% in men and from 2 to 5% in women. Its deleterious consequences such as traffic accidents, cardiovascular complications increasing morbidity and mortality, make it a major health problem. Apart from obesity (a major risk factor for OSAHS), hypothyroid patients are prone to reveal this phenotype. Although hypothyroidism seems an acknowledged risk factor for OSAHS, some authors report the lack of clinically relevant association. The argument partly depends on the increased prevalence of hypothyroidism in OSAHS patients, but the epidemiological data is limited and somehow inconsistent; even less is known about sub-clinical hypothyroidism in OSAHS patients. Even if frequency of overt and sub-clinical hypothyroidism in OSAHS patients is comparable to the general population, screening for it seems beneficial, as hormone replacement therapy may improve sleep disordered breathing. Unfortunately, this favorable outcome was found only in a few studies with limited number of patients with hypothyroidism. Yet, despite the lack of international guidelines and no large multicentre studies on the topic available, we think that TSH screening might prove beneficial in vast majority of OSAHS patients.

Evaluation of COVID-19 Effect on Mental Health, Self-Harm, and Suicidal Behaviors in Children and Adolescents Population.

OBJECTIVES: The impact of the COVID-19 pandemic on the psychological state of the under-18 population includes an increased risk of psychopathological symptoms development and exacerbation of already present psychiatric disorders. This study aimed to assess the prevalence of mental health problems in Polish children and adolescents with a focus on suicidal and self-harm behavior with the impact of the pandemic. METHODS: The questionnaire collected demographic data, information regarding mental states and psychopathological symptoms, history of self-harm and suicidal behaviors, as well as the experience of psychological, and physical violence, and suicidal self-harm behaviors before and during the COVID-19 pandemic. RESULTS: In the final analysis, 782 responses were included. Self-evaluation of general and mental health scores was significantly lower during the pandemic among children (both p < 0.001) and adolescents (both p < 0.001). Moreover, general and mental health scores were lower among adolescents compared to children before (both p < 0.001) and during (both p < 0.001) the pandemic. The frequency of seeking help because of mental health problems increased during the pandemic among children and adolescents, while no changes were observed in the prevalence of psychiatric hospitalizations in either of the populations (p = 0.317 and p = 1.00, respectively). Out of autoregressive behaviors among children during the pandemic period, only the frequency of thinking about death increased (p = 0.038). No suicidal attempts were undertaken by children in either of the evaluated time periods. The presence of all autoaggressive behaviors was greater among adolescents compared to children both before and during the COVID-19 pandemic (all p<0.05). CONCLUSIONS: A subjective decrease in psychophysical well-being, an increase in the frequency of seeking mental health help during the pandemic, as well as an increased prevalence of depressive and anxiety symptoms were observed in the under-18 population as a potential consequence of the COVID-19 pandemic and related socioeconomic changes. The marked increase in self-harm behavior in the adolescent population (age > 12) and the marked increase in the frequency of death thinking in children (age ≤ 12) suggests the need for greater awareness and easier access to professional help from mental health specialists, particularly in a time of unprecedented stress and social isolation.

Association between glucose metabolism, the circadian cycle and hypoxia: Evaluation of the NPAS2 and Rev-Erb-α protein serum levels in obstructive sleep apnea patients - a pilot study.

BACKGROUND: Obstructive sleep apnea (OSA) is one of the risk factors for diabetes mellitus type 2 (DM2). As OSA is associated with the disruption of the circadian rhythm, it affects circadian clock proteins, including neuronal PAS domain protein 2 (NPAS2) and nuclear receptor subfamily 1 group D member 1 (Rev-Erb-α). These proteins have been shown to be related to metabolic abnormalities, i.a., insulin resistance. OBJECTIVES: The present pilot study aimed to investigate the NPAS2 and Rev-Erb-α protein serum levels in the groups of patients with severe OSA and severe OSA+DM2 in comparison with healthy controls, taking into account correlations with polysomnography (PSG) parameters (e.g., oxygen saturation (SpO2) variables). MATERIAL AND METHODS: A total of 40 participants were included in the study. They were split into 3 groups as follows: the OSA group (n = 17; apnea-hypopnea index (AHI) >30, no DM2); the OSA+DM2 group (n = 7; AHI > 30 and DM2); and the control group (n = 16; AHI < 5, no DM2). All participants underwent a nocturnal PSG examination and had their blood collected the following morning. The serum levels of NPAS2 and Rev-Erb-α proteins were assessed using the enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean NPAS2 protein level was significantly lower in the OSA group as compared to healthy individuals (p = 0.017). Additionally, the OSA group presented with lower NPAS2 protein levels as compared to the OSA+DM2 group, but only a tendency was observed (p = 0.094). No differences in the Rev-Erb-α protein concentration were noticed. Furthermore, a negative correlation between AHI during rapid eye movement (REM) sleep and the NPAS2 protein serum level was observed (r = -0.478; p = 0.002). CONCLUSIONS: Serum NPAS2 protein might be involved in metabolic dysregulation present among OSA patients, while the mechanism itself may be associated with REM sleep.

Evaluation of daytime sleepiness and insomnia symptoms in OSA patients with a characterization of symptom-defined phenotypes and their involvement in depression comorbidity-a cross-sectional clinical study.

Introduction: Recent research highlights the significance of insomnia and sleepiness, shifting from obstructive sleep apnea (OSA) severity and sleep structure, in defining OSA phenotypes. Objectives: This study aimed to characterize insomnia and sleepiness associated with OSA phenotypes and assess their involvement in depression symptoms (DS) in OSA. Materials and methods: This cross-sectional, clinical study included 181 participants who underwent polysomnography (PSG) and filled out questionnaires, including the Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Beck Depression Index (BDI). They were categorized into phenotypes: insomnia-sleepiness (I + S; ESS ≥ 11; ISI ≥ 15; n = 20), sleepiness (S; ESS ≥ 11; ISI < 15; n = 22), insomnia (I; ESS < 11; ISI ≥ 15), and asymptomatic (A; ESS < 11; ISI<15; n=55). Results: A linear regression model for the BDI score (R2 = 0.357, p < 0.001) included ISI score and subjective-to-objective sleep latency ratio. The ISI score was a predictive factor for mild and moderate DS [OR = 1.23 (95% CI: 1.09-1.38), p < 0.001 and OR = 1.39 (95% CI: 1.13-1.72), p = 0.002]. The I and I + S phenotypes are characterized by higher BDI scores (p < 0.001 and p = 0.02), longer subjective sleep latency (p = 0.008 and p = 0.04), and shorter subjective total sleep time (TST; p = 0.049 and p = 0.006) compared to A. Furthermore, the I and I + S groups had shorter subjective TST than S (p = 0.03 and p = 0.047). The I and I + S had higher BDI scores than A (p < 0.001 and p = 0.02, respectively) and S (p < 0.001 and p = 0.02, respectively). The I phenotype was associated with the risk of mild and moderate DS (OR = 5.61 (95% CI: 1.91-16.53), p < 0.001 and OR = 9.55 (95% CI: 1.81-50.48), p = 0.008 respectively). Moreover, the I + S phenotype presented an even greater risk for mild DS (OR = 10.29 (95% CI: 2.95-35.85), p < 0.001). Conclusion: Using clinical features for OSA phenotyping holds promise for finding OSA individuals with increased risk for DS occurrence.

The effect of sleep and its restriction on selected inflammatory parameters.

Insufficient sleep duration may lead to a series of immune dysfunctions. One of the factors influencing this effect could be physical activity (PA). The study aimed to assess the impact of deprivation of sleep (DS) on selected inflammatory parameters. Seventy-seven participants completed the protocol consisting of polysomnography (PSG) conducted in a sleep laboratory and DS, monitored with an actigraph. PA was assessed with actigraphy, which categorized participants as active or inactive. White blood cells (WBC) values negatively correlated with sleep efficiency based on sleep diaries and PSG parameters (total sleep time, sleep efficiency, and REM duration), but regression analysis showed that WBC depends only on the sleep diary parameter. Granulocytes (GRA) positively correlated with REM latency, and negatively with sleep efficiency. After DS, all participants exhibited an elevated GRA count. The number of WBC and GRA increased also in the active group; inactive participants showed no changes in inflammatory parameters. The overall number of WBC depends primarily on the quality of sleep over a period of several days. Under the influence of sleep deprivation, the number of GRA increases, but the number of leukocytes depends on the level of physical activity during DS.

The Relationship between Sleep Parameters Measured by Polysomnography and Selected Neurotrophic Factors.

BACKGROUND: The molecular underpinnings of insufficient sleep remain underexplored, with disruptions in the neurotrophic signaling pathway emerging as a potential explanation. Neurotrophins (NTs), including brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3), neurotrophin 4 (NT4), and glial-cell-line-derived growth factor (GDNF), play crucial roles in nerve cell growth and repair. However, their associations with sleep patterns are poorly understood. This study aimed to investigate the relationship between the chosen neurotrophins and objective sleep parameters. METHODS: The study involved 81 participants subjected to polysomnography (PSG). Blood samples were collected after PSG. The mRNA expression and serum protein concentrations of BDNF, GDNF, NT3, and NT4 were measured using real-time quantitative reverse-transcription PCR (qRT-PCR) or enzyme-linked immunosorbent assay (ELISA) methods, respectively. RESULTS: BDNF and NT3 proteins were negatively correlated with NREM events, while NT4 protein positively correlated with REM events. Electroencephalography power analysis revealed BDNF protein's negative correlation with delta waves during rapid eye movement and non-rapid eye movement sleep. CONCLUSION: The study highlights associations between neurotrophins and sleep, emphasizing BDNF's role in regulating NREM and REM sleep. The EEG power analysis implicated BDNF in delta wave modulation, shedding light on potential neurotrophic mechanisms underlying sleep effects on cognitive and mood processes.

Interactions between neurotrophins, mood, and physical activity under the conditions of sleep deprivation.

Sleep deprivation (DS) is the forced elimination of sleep. While brain-derived neurotrophic factor (BDNF) has been extensively studied in the context of in mood changes following DS, the role of other neurotrophins remains elusive. This study explores the impact of DS on BDNF, glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT3), and neurotrophin-4 (NT4) at mRNA and protein level, considering their potential links to mood disturbances. The study involved 81 participants subjected to polysomnography (PSG) and DS. Blood samples, mood assessments, and actigraphy data were collected twice, after PSG and DS. NT mRNA expression and serum protein concentrations of BDNF, GDNF, NT3, and NT4 were measured. Participants were divided into Responders and Non-Responders based on mood improvement after DS. DS reduced BDNF mRNA expression in all participants, with no change in serum BDNF protein. GDNF protein decreased in Non-Responders, while Responders exhibited reduced GDNF mRNA. NT3 protein increased in both groups, while NT3 mRNA decreased in Respondents. NT4 protein rose universally post-DS, but NT4 mRNA remained unchanged. Physical activity (PA) negatively correlated with mRNA expression of BDNF, GDNF, and NT3 post-DS. The study's short DS duration and exclusion of immature NT forms limit comprehensive insights. GDNF, together with NT3, might play an important role in mood response to DS. PA during DS seems to impair the mRNA expression of NTs in leukocytes. Future studies on the subject of sleep deprivation might consider investigating the relationship between BDNF and NT4 in the context of their apparent redundancy.