{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:42:48Z","timestamp":1790016168646,"version":"4.0.1"},"reference-count":45,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre (Poland)","doi-asserted-by":"publisher","award":["2018\/31\/N\/NZ5\/03931"],"award-info":[{"award-number":["2018\/31\/N\/NZ5\/03931"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-1\u03b1, 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 \u2265 30) and healthy control (n = 20; AHI &lt; 5) based on the apnea\u2013hypopnea index (AHI). All participants had their peripheral blood collected in the evening before and the morning after the PSG. BDNF, proBDNF, and HIF-1\u03b1 protein concertation measurements were performed using ELISA. No differences were found in BDNF, proBDNF, and HIF-1\u03b1 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 (\u00df = \u22120.389, p = 0.023) and the mean SpO2 of desaturations during sleep (\u00df = \u22120.577, p = 0.002). This model accounted for 63.3% of the variability in the morning BDNF protein level (F = 14.639, p &lt; 0.001). The morning proBDNF protein level was predicted by age (\u00df = \u22120.395, p = 0.033) and HIF-1\u03b1 morning protein level (\u00df = \u22123.192, 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.<\/jats:p>","DOI":"10.3390\/ijms232314876","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T07:38:49Z","timestamp":1669621129000},"page":"14876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Evaluation of HIF-1 Involvement in the BDNF and ProBDNF Signaling Pathways among Obstructive Sleep Apnea Patients"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-6488","authenticated-orcid":false,"given":"Agata","family":"Gabryelska","sequence":"first","affiliation":[{"name":"Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 90-419 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2122-0304","authenticated-orcid":false,"given":"Marcin","family":"Sochal","sequence":"additional","affiliation":[{"name":"Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 90-419 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1001\/jama.2020.3514","article-title":"Diagnosis and Management of Obstructive Sleep Apnea: A review","volume":"323","author":"Gottlieb","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.smrv.2016.07.002","article-title":"Prevalence of obstructive sleep apnea in the general population: A systematic review","volume":"34","author":"Senaratna","year":"2017","journal-title":"Sleep Med. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/S2213-2600(15)00043-0","article-title":"Prevalence of sleep-disordered breathing in the general population: The HypnoLaus study","volume":"3","author":"Heinzer","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"985","DOI":"10.5664\/jcsm.7166","article-title":"High negative predictive value of normal body mass index for obstructive sleep apnea in the lateral sleeping position","volume":"14","author":"Mokros","year":"2018","journal-title":"J. Clin. Sleep Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1378\/chest.09-0360","article-title":"Interactions between Obesity and Obstructive Sleep Apnea: Implications for Treatment","volume":"137","author":"Caples","year":"2010","journal-title":"Chest"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.chest.2017.05.009","article-title":"Obstructive Sleep Apnea and Diabetes: A State of the Art Review","volume":"152","author":"Reutrakul","year":"2017","journal-title":"Chest"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gabryelska, A., Chrzanowski, J., Sochal, M., Kaczmarski, P., Turkiewicz, S., Ditmer, M., Karuga, F.F., Czupryniak, L., and Bia\u0142asiewicz, P. (2021). Nocturnal Oxygen Saturation Parameters as Independent Risk Factors for Type 2 Diabetes Mellitus among Obstructive Sleep Apnea Patients. J. Clin. Med., 10.","DOI":"10.1183\/23120541.sleepandbreathing-2021.66"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000988","article-title":"Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement from the American Heart Association","volume":"144","author":"Yeghiazarians","year":"2021","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Turkiewicz, S., Ditmer, M., Sochal, M., Bia\u0142asiewicz, P., Strzelecki, D., and Gabryelska, A. (2021). Obstructive Sleep Apnea as an Acceleration Trigger of Cellular Senescence Processes through Telomere Shortening. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212536"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.sleep.2012.03.002","article-title":"Obstructive sleep apnea and the risk of autoimmune diseases: A longitudinal population-based study","volume":"13","author":"Kang","year":"2012","journal-title":"Sleep Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kuna, K., Szewczyk, K., Gabryelska, A., Bia\u0142asiewicz, P., Ditmer, M., Strzelecki, D., and Sochal, M. (2022). Potential Role of Sleep Deficiency in Inducing Immune Dysfunction. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092159"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"153","DOI":"10.5664\/jcsm.6908","article-title":"Patients with Obstructive Sleep Apnea Are Over Four Times More Likely to Suffer From Psoriasis Than the General Population","volume":"14","author":"Gabryelska","year":"2018","journal-title":"J. Clin. Sleep Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.maturitas.2020.06.002","article-title":"Obstructive sleep apnea and depression: A systematic review and meta-analysis","volume":"142","author":"Edwards","year":"2020","journal-title":"Maturitas"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105","DOI":"10.5664\/jcsm.5406","article-title":"The Prevalence of Depression among Untreated Obstructive Sleep Apnea Patients Using a Standardized Psychiatric Interview","volume":"12","author":"Pack","year":"2016","journal-title":"J. Clin. Sleep Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.jsmc.2013.04.004","article-title":"Insomnia and Obstructive Sleep Apnea","volume":"8","author":"Ong","year":"2013","journal-title":"Sleep Med. Clin."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"190080","DOI":"10.1183\/16000617.0080-2019","article-title":"Management of insomnia in sleep disordered breathing","volume":"28","author":"Janssen","year":"2019","journal-title":"Eur. Respir. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5042","DOI":"10.1172\/JCI137560","article-title":"Hypoxia-inducible factors and obstructive sleep apnea","volume":"130","author":"Prabhakar","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.5664\/jcsm.8682","article-title":"Patients with obstructive sleep apnea present with chronic upregulation of serum HIF-1\u03b1 protein","volume":"16","author":"Gabryelska","year":"2020","journal-title":"J. Clin. Sleep Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"158","DOI":"10.20452\/pamw.15220","article-title":"Serum Hypoxia-Inducible Factor-1\u03b1 protein level as a diagnostic marker of obstructive sleep apnea","volume":"130","author":"Gabryelska","year":"2020","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_20","first-page":"47","article-title":"Potential inflammatory markers in obstructive sleep apnea-hypopnea syndrome","volume":"17","author":"Lu","year":"2017","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e12995","DOI":"10.1111\/jsr.12995","article-title":"Influence of one-night CPAP therapy on the changes of HIF-1\u03b1 protein in OSA patients: A pilot study","volume":"29","author":"Gabryelska","year":"2020","journal-title":"J. Sleep Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hartman, W., Helan, M., Smelter, D., Sathish, V., Thompson, M., Pabelick, C.M., Johnson, B., and Prakash, Y.S. (2015). Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129489"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sochal, M., Ditmer, M., Gabryelska, A., and Bia\u0142asiewicz, P. (2022). The Role of Brain-Derived Neurotrophic Factor in Immune-Related Diseases: A Narrative Review. J. Clin. Med., 11.","DOI":"10.3390\/jcm11206023"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s10571-017-0510-4","article-title":"BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity","volume":"38","author":"Lietzau","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3389\/fncel.2020.00082","article-title":"The Role of BDNF on Neural Plasticity in Depression","volume":"14","author":"Yang","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Emon, P.Z., Das, R., Nishuty, N.L., Qusar, M.M.A.S., Bhuiyan, M.A., and Islam, R. (2020). Reduced serum BDNF levels are associated with the increased risk for developing MDD: A case\u2013control study with or without antidepressant therapy. BMC Res. Notes, 13.","DOI":"10.1186\/s13104-020-04952-3"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7260130","DOI":"10.1155\/2017\/7260130","article-title":"Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection","volume":"2017","author":"Phillips","year":"2017","journal-title":"Neural Plast."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3109\/07853890.2015.1131327","article-title":"BDNF in sleep, insomnia, and sleep deprivation","volume":"48","author":"Schmitt","year":"2016","journal-title":"Ann. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s11064-019-02914-1","article-title":"The Brain-Derived Neurotrophic Factor: Missing Link between Sleep Deprivation, Insomnia, and Depression","volume":"45","author":"Rahmani","year":"2020","journal-title":"Neurochem. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"641278","DOI":"10.3389\/fpsyt.2021.641278","article-title":"Decreased Peripheral BDNF Levels and Cognitive Impairment in Late-Life Schizophrenia","volume":"12","author":"Huo","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16442","DOI":"10.1038\/s41598-020-73576-1","article-title":"Lower brain-derived neurotrophic factor levels are associated with age-related memory impairment in community-dwelling older adults: The Sefuri study","volume":"10","author":"Mizoguchi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e13978","DOI":"10.1111\/nmo.13978","article-title":"Brain-derived neurotrophic factor is elevated in the blood serum of Crohn\u2019s disease patients, but is not influenced by anti-TNF-\u03b1 treatment\u2014A pilot study","volume":"33","author":"Sochal","year":"2021","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kheirandish-Gozal, L., and Gozal, D. (2019). Obstructive Sleep Apnea and Inflammation: Proof of Concept Based on Two Illustrative Cytokines. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030459"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s11325-010-0415-7","article-title":"Effects of obstructive sleep apnea on serum brain-derived neurotrophic factor protein, cortisol, and lipid levels","volume":"15","author":"Panaree","year":"2011","journal-title":"Sleep Breath."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"zsz145","DOI":"10.1093\/sleep\/zsz145","article-title":"Effect of continuous positive airway pressure on inflammatory, antioxidant, and depression biomarkers in women with obstructive sleep apnea: A randomized controlled trial","volume":"42","author":"Troncoso","year":"2019","journal-title":"Sleep"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e13035","DOI":"10.1111\/jsr.13035","article-title":"Interleukin 6 as a marker of depression in women with sleep apnea","volume":"30","author":"Gozal","year":"2021","journal-title":"J. Sleep Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"835515","DOI":"10.3389\/fmed.2021.835515","article-title":"The Role of Brain-Derived Neurotrophic Factor in Obstructive Sleep Apnea and Endothelial Function in a Pediatric Population with Obesity","volume":"8","author":"Makhout","year":"2022","journal-title":"Front. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.sleep.2021.11.018","article-title":"Inflammatory markers and BDNF in obstructive sleep apnea (OSA) in Parkinson\u2019s disease (PD)","volume":"90","author":"Kaminska","year":"2022","journal-title":"Sleep Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Flores, K.R., Viccaro, F., Aquilini, M., Scarpino, S., Ronchetti, F., Mancini, R., Di Napoli, A., Scozzi, D., and Ricci, A. (2020). Protective role of brain derived neurotrophic factor (BDNF) in obstructive sleep apnea syndrome (OSAS) patients. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0227834"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1002\/lio2.683","article-title":"The evaluation of serum brain-derived neurotrophic factor and neurofilament light chain levels in patients with obstructive sleep apnea syndrome","volume":"6","author":"Arslan","year":"2021","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3389\/fncel.2019.00363","article-title":"Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain","volume":"13","author":"Miranda","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5368","DOI":"10.1523\/JNEUROSCI.6251-09.2010","article-title":"Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume","volume":"30","author":"Erickson","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_43","first-page":"36","article-title":"Involvement of BDNF in age-dependent alterations in the hippocampus","volume":"2","year":"2010","journal-title":"Front. Aging Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.neurobiolaging.2004.03.002","article-title":"The impact of age, weight and gender on BDNF levels in human platelets and plasma","volume":"26","author":"Lommatzsch","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"479","DOI":"10.5664\/jcsm.6506","article-title":"Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: An American academy of sleep medicine clinical practice guideline","volume":"13","author":"Kapur","year":"2017","journal-title":"J. Clin. Sleep Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14876\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:28:28Z","timestamp":1760146108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,28]]},"references-count":45,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232314876"],"URL":"https:\/\/doi.org\/10.3390\/ijms232314876","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,28]]}}}