Exploring differences in signaling pathways of the circadian clock and neuromodulators in obstructive sleep apnea

Abstract

Abstract Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurring upper airway obstructions, leading to disrupted sleep and systemic complications. The complexity of OSA suggests intricate interactions between neuromodulators and circadian clock genes. This study aimed to explore the expression levels of circadian rhythm genes and neurotrophins (NTs) in OSA patients compared to controls. Participants (166 OSA patients, 64 controls) were enrolled. Blood samples collected post-polysomnography (PSG), underwent RNA extraction from peripheral blood lymphocytes and RT-PCR was performed for gene expression analysis. In the OSA group, the expression of BMAL1, CLOCK, CRY1, PER1, NPAS2, NR1D1, and HIF-1β was positively correlated with BDNF expression (p < 0.05 for all). Conversely, in the control group, only PER1 mRNA showed a correlation with BDNF expression (R = 0.280, p = 0.017). NF-κβ expression demonstrated a positive correlation with BMAL1, CLOCK, CRY1, PER1, NPAS2, NR1D1, HIF-1α, and HIF-1β expressions in both groups (p < 0.05 for all). HIF-1α and HIF1-β mRNA expressions were positively correlated with BMAL1, CLOCK, CRY1, PER1, NPAS2, and NR1D1 expressions regardless of the presence of OSA (p < 0.05 for all). The study underscores the intricate interactions among circadian rhythm genes, NTs, and transcription factors in OSA, providing a basis for potential targeted therapeutic interventions.

Keywords

• Neurotrophins
• Neuromodulators
• Circadian clock
• OSA
• BDNF