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.

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.

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.

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.

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.

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.

Investigating the Role of BDNF in Insomnia: Current Insights.

Insomnia is a common disorder defined as frequent and persistent difficulty initiating, maintaining, or going back to sleep. A hallmark symptom of this condition is a sense of nonrestorative sleep. It is frequently associated with other psychiatric disorders, such as depression, as well as somatic ones, including immunomediated diseases. BDNF is a neurotrophin primarily responsible for synaptic plasticity and proper functioning of neurons. Due to its role in the central nervous system, it might be connected to insomnia of multiple levels, from predisposing traits (neuroticism, genetic/epigenetic factors, etc.) through its influence on different modes of neurotransmission (histaminergic and GABAergic in particular), maintenance of circadian rhythm, and sleep architecture, and changes occurring in the course of mood disturbances, substance abuse, or dementia. Extensive and interdisciplinary evaluation of the role of BDNF could aid in charting new areas for research and further elucidate the molecular background of sleep disorder. In this review, we summarize knowledge on the role of BDNF in insomnia with a focus on currently relevant studies and discuss their implications for future projects.

Influence of glutamatergic and GABAergic neurotransmission on obstructive sleep apnea.

Glutamate and γ-aminobutyric acid (GABA) are the two main neurotransmitters in the human brain. The balance between their excitatory and inhibitory functions is crucial for maintaining the brain's physiological functions. Disturbance of glutamatergic or GABAergic neurotransmission leads to serious health problems including neurodegeneration, affective and sleep disorders. Both GABA and glutamate are involved in the control of the sleep-wake cycle. The disturbances in their function may cause sleep and sleep-related disorders. Obstructive sleep apnea (OSA) is the most common sleep respiratory disorder and is characterized by repetitive collapse of the upper airway resulting in intermittent hypoxia and sleep fragmentation. The complex pathophysiology of OSA is the basis of the development of numerous comorbid diseases. There is emerging evidence that GABA and glutamate disturbances may be involved in the pathogenesis of OSA, as well as its comorbidities. Additionally, the GABA/glutamate targeted pharmacotherapy may also influence the course of OSA, which is important in the implementation of wildly used drugs including benzodiazepines, anesthetics, and gabapentinoids. In this review, we summarize current knowledge on the influence of disturbances in glutamatergic and GABAergic neurotransmission on obstructive sleep apnea.

Shedding light on neurofilament involvement in cognitive decline in obstructive sleep apnea and its possible role as a biomarker.

Obstructive sleep apnea is one of the most common sleep disorders with a high estimated global prevalence and a large number of associated comorbidities in general as well as specific neuropsychiatric complications such as cognitive impairment. The complex pathogenesis and effects of the disorder including chronic intermittent hypoxia and sleep fragmentation may lead to enhanced neuronal damage, thereby contributing to neuropsychiatric pathologies. Obstructive sleep apnea has been described as an independent risk factor for several neurodegenerative diseases, including Alzheimer's disease and all-cause dementia. The influence of obstructive sleep apnea on cognitive deficits is still a topic of recent debate, and several mechanisms, including neurodegeneration and depression-related cognitive dysfunction, underlying this correlation are taken into consideration. The differentiation between both pathomechanisms of cognitive impairment in obstructive sleep apnea is a complex clinical issue, requiring the use of multiple and costly diagnostic methods. The studies conducted on neuroprotection biomarkers, such as brain-derived neurotrophic factors and neurofilaments, are recently gaining ground in the topic of cognition assessment in obstructive sleep apnea patients. Neurofilaments as neuron-specific cytoskeletal proteins could be useful non-invasive indicators of brain conditions and neurodegeneration, which already are observed in many neurological diseases leading to cognitive deficits. Additionally, neurofilaments play an important role as a biomarker in other sleep disorders such as insomnia. Thus, this review summarizes the current knowledge on the involvement of neurofilaments in cognitive decline and neurodegeneration in obstructive sleep apnea patients as well as discusses its possible role as a biomarker of these changes.

Clinical and Laboratory Characteristics of Anaemia in Hospitalized Patients with Inflammatory Bowel Disease.

Anaemia is the most common extraintestinal manifestation of inflammatory bowel disease (IBD). Due to its multifactorial etiopathogenesis, the differential diagnosis and treatment of anaemia in IBD is a significant clinical problem. The main aim of our study was to assess the usefulness of laboratory parameters, including hepcidin, in differential diagnoses of anaemia in hospitalized IBD patients. This study also estimated the impact of anaemia on the length of hospitalization and its relationship with clinical data of analyzed patients. The study included 118 adult patients diagnosed with IBD-55 with ulcerative colitis (UC) and 63 with Crohn's disease (CD). Anaemia was significantly more frequent in patients with CD-42 (66.7%)-compared to 31 (56.4%) patients with UC (p = 0.033). The prevalence of anaemia increased significantly with the severity of IBD and the extent of inflammatory changes in the endoscopic examination. Hospitalization time was significantly longer in patients with anaemia, especially in the group with UC. Ferritin concentrations < 30 ng/mL were found only in 15 (20.55%) IBD patients (9 with UC and 6 with CD), and ferritin < 100 ng/mL was observed in 22 (30.14%) patients, equally frequent with UC and CD (p > 0.05). Significantly higher concentrations of transferrin were observed in patients with anaemia in the course of UC compared to CD (2.58 ± 0.90 g/L vs. 2.15 ± 0.82 g/L; p = 0.037). On the other hand, saturation of transferrin < 16% was equally common in UC and CD patients. In our study, hepcidin levels in anaemic UC patients were significantly lower compared to UC without anaemia (p = 0.042), with no similar differences in CD independently of anaemia presence (p = 0.565). To conclude, we observed a high incidence of anaemia in patients with IBD and its significant impact on the length of hospitalization in UC. Routinely determined single laboratory parameters are not sufficient for the differential diagnosis of anaemia, and a complex laboratory assessment, including of hepcidin levels, is necessary for the full picture of anaemia in the course of IBD.

Clinical Significance of Erythroferrone and Bone Morphogenetic Protein-6 in Patients with Anemia in the Course of Inflammatory Bowel Disease.

In recent years, a steady increase in the incidence of inflammatory bowel diseases (IBD) has been observed with anemia as their most common extraintestinal symptom. Erythroferrone and Bone Morphogenetic Protein 6 (BMP-6) are recently identified cytokines involved in the process of increased erythropoiesis in anemia of various pathomechanisms. The aim of this study was to analyze the concentration of erythroferrone and BMP-6 in IBD patients in relation to clinical and laboratory data. The study comprised 148 patients: 118 with IBD, including 73 (61.85%) diagnosed with anemia (42 with Crohn's disease (CD) (66.7%) and 31 (56.4%) with ulcerative colitis (UC)) and 30 as a control group. The erythroferrone concentration was significantly higher in IBD patients with anemia (p = 0.009) and higher in UC patients both with and without anemia (p = 0.018), compared to the control group. In CD, no similar difference was observed between patients with and without anemia. Regarding BMP-6, higher levels were found in CD patients with anemia compared to the control group (p = 0.021). The positive correlation between BMP-6 and iron concentration in UC was also noticed. In conclusion, we confirm an increase in erythroferrone concentration in the entire group of IBD patients with anemia, while BMP-6 levels were higher only in anemic CD patients. Due to the clinical importance of anemia in IBD, this problem is worth further analysis and research projects.

Evaluation of cognitive and psychomotor faculties in relation to mood-related symptoms under the conditions of sleep deprivation.

Introduction: Deprivation of sleep (DS) has been associated with changes in mood and cognitive function, rapidly but transiently improving the severity of depression symptoms. However, it remains unclear whether there are differences in performance between DS responders and non-responders. The relationship between DS, mood, cognitive, and psychomotor function is also poorly understood. Methods: Participants (n = 77) underwent a baseline assessment of sleep under the control of polysomnography (PSG). Later they were subjected to DS with actigraphy monitoring. Evaluation of mood as well as completing a battery of tests assessing cognitive functions and eye-hand coordination was conducted four times, pre/post PSG and DS. Participants were further divided into respondents (RE, n = 48) and non-respondents (NR, n = 29) depending on alleviation of depression symptoms severity following DS. Results: All participants exhibited increased response speed to visual triggers after DS compared to baseline (p = 0.024). Psychomotor vigilance test (PVT) results remained intact in the RE, whereas it was increased in the NR (p = 0.008). Exposure time in the eye-hand coordination test improved in both groups, but total error duration was reduced only in RE individuals (p < 0.001, p = 0.009 for RE and NR, respectively). All subjects were more proficient at trail-making test (p ≤ 0.001 for Part 1 and 2 in all, NR, RE). Stroop test also improved regardless of mood changes after DS (p = 0.007, p = 0.008 for Part 1 and 2, respectively); cognitive interference remained at a similar level within groups (p = 0.059, p = 0.057 for NR and RE, respectively). A positive correlation was observed between the difference in PSG morning/DS morning depression severity and vigilance (R = 0.37, p = 0.001, R = 0.33, p = 0.005, for error duration eye-hand coordination test and PVT total average score, respectively). Conclusion: RE tend to maintain or improve cognitive function after DS, oppositely to NR. Vigilance in particular might be tightly associated with changes in depression symptoms after DS. Future studies should examine the biological basis behind the response to sleep loss.

The role of microRNAs in pathophysiology and diagnostics of metabolic complications in obstructive sleep apnea patients.

Obstructive sleep apnea (OSA) is one of the most common sleep disorders, which is characterized by recurrent apneas and/or hypopneas occurring during sleep due to upper airway obstruction. Among a variety of health consequences, OSA patients are particularly susceptible to developing metabolic complications, such as metabolic syndrome and diabetes mellitus type 2. MicroRNAs (miRNAs) as epigenetic modulators are promising particles in both understanding the pathophysiology of OSA and the prediction of OSA complications. This review describes the role of miRNAs in the development of OSA-associated metabolic complications. Moreover, it summarizes the usefulness of miRNAs as biomarkers in predicting the aforementioned OSA complications.

Relation between Selected Sleep Parameters, Depression, Anti-Tumor Necrosis Factor Therapy, and the Brain-Derived Neurotrophic Factor Pathway in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) patients often have sleep and mood disorders. Brain-derived neurotrophic factor (BDNF) and proBDNF were shown to modulate interactions between the central nervous system and the gastrointestinal tract, possibly contributing to psychological issues. Anti-tumor necrosis factor (TNF) therapy in IBD can alter BDNF expression and further affect the brain-gut axis. Eighty IBD patients and 44 healthy controls (HCs) were enrolled and divided into subsets based on disease activity and condition (ulcerative colitis (UC)/Crohn's disease (CD)). Questionnaires evaluating sleep parameters and depression as well as venous blood were collected. The IBD group had a lower expression of BDNF mRNA, but higher proBDNF and BDNF protein concentration than HCs. The UC group had a higher BDNF protein concentration than the CD. BDNF protein was positively correlated to sleep efficiency in the IBD group. Depression severity was associated positively with BDNF mRNA and negatively with BDNF protein in the remission group. Anti-TNF therapy enhanced BDNF mRNA expression. The BDNF pathway might be disturbed in IBD, linking it to sleep disorders and depression. Systemic inflammation could be the main cause of this disruption. BDNF mRNA is a more reliable parameter than protein due to numerous post-translational modifications.

The Effect of Serotonin Transmission on Depressive and Insomnia Symptoms in Inflammatory Bowel Diseases.

The serotonergic pathway may impact the pathogenesis and the course of inflammatory bowel diseases (IBDs). The aim of this study was to investigate the relationship between 5-HT, the serotonin transporter (SERT), and the clinical course of the disease with the occurrence of sleep and mood disorders. Participants completed sleep questionnaires and the Beck Depression Inventory (BDI). Serum 5-HT, SERT protein expression, and mRNA levels were quantified. Additionally, patients treated with anti-TNF therapy were examined before and after treatment. In this study, 77 patients with IBD and 41 healthy controls (HCs) were enrolled and 24 of them were treated with anti-TNF therapy. Patients with IBD had higher 5-HT levels and SERT protein expression than the HCs, but not mRNA SERT levels (p = 0.015, p = 0.001, p = 0.069, respectively). Similar results were obtained for patients in the active state of the disease compared to the non-active state. There was a positive relationship between insomnia severity and SERT protein expression. BDI did not correlate with serotonin or SERT. After anti-TNF therapy, only 5-HT levels were decreased. 5-HT and SERT protein are overexpressed in active IBD and may represent a candidate for novel disease activity biomarkers. The correlation between the SERT protein level and the severity of insomnia symptoms might be among the underlying biochemical factors of sleep disturbances. Anti-TNF treatment might contribute to the reduction in 5-HT levels.