Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, Pólo I, Coimbra 3004-504, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; PhD Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal
Janina Hesse
Institute for Theoretical Biology (ITB), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany; Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumour Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany; Department of Human Medicine, Institute for Systems Medicine and Bioinformatics, MSH Medical School Hamburg-University of Applied Sciences and Medical University, Am Kaiserkai 1, Hamburg 20457, Germany
Müge Yalçin
Institute for Theoretical Biology (ITB), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany; Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumour Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany
Bárbara Santos
Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, Pólo I, Coimbra 3004-504, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal
Catarina Carvalhas-Almeida
Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, Pólo I, Coimbra 3004-504, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal
Mafalda Ferreira
Sleep Medicine Centre, Coimbra Hospital and University Centre, Coimbra, Portugal
Joaquim Moita
Sleep Medicine Centre, Coimbra Hospital and University Centre, Coimbra, Portugal
Angela Relógio
Institute for Theoretical Biology (ITB), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany; Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumour Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany; Department of Human Medicine, Institute for Systems Medicine and Bioinformatics, MSH Medical School Hamburg-University of Applied Sciences and Medical University, Am Kaiserkai 1, Hamburg 20457, Germany; Corresponding authors.
Cláudia Cavadas
Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, Pólo I, Coimbra 3004-504, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Corresponding authors.
Ana Rita Álvaro
Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, Pólo I, Coimbra 3004-504, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal; Corresponding authors.
Background: Obstructive Sleep Apnea (OSA) is a highly prevalent and underdiagnosed sleep disorder. Recent studies suggest that OSA might disrupt the biological clock, potentially causing or worsening OSA-associated comorbidities. However, the effect of OSA treatment on clock disruption is not fully understood. Methods: The impact of OSA and short- (four months) and long-term (two years) OSA treatment, with Continuous Positive Airway Pressure (CPAP), on the biological clock was investigated at four time points within 24 h, in OSA patients relative to controls subjects (no OSA) of the same sex and age group, in a case-control study. Plasma melatonin and cortisol, body temperature and the expression levels and rhythmicity of eleven clock genes in peripheral blood mononuclear cells (PBMCs) were assessed. Additional computational tools were used for a detailed data analysis. Findings: OSA impacts on clock outputs and on the expression of several clock genes in PBMCs. Neither short- nor long-term treatment fully reverted OSA-induced alterations in the expression of clock genes. However, long-term treatment was able to re-establish levels of plasma melatonin and cortisol and body temperature. Machine learning methods could discriminate controls from untreated OSA patients. Following long-term treatment, the distinction between controls and patients disappeared, suggesting a closer similarity of the phenotypes. Interpretation: OSA alters biological clock-related characteristics that differentially respond to short- and long-term CPAP treatment. Long-term CPAP was more efficient in counteracting OSA impact on the clock, but the obtained results suggest that it is not fully effective. A better understanding of the impact of OSA and OSA treatment on the clock may open new avenues to OSA diagnosis, monitoring and treatment.
