Clock gene dysfunction in patients with obstructive sleep apnoea syndrome.
N Burioka1, S Koyanagi, M Endo
1Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1 Nishimachi, Yonago 683-8504, Japan. burioka@grape.med.tottori-u.ac.jp
The European Respiratory Journal
|March 7, 2008
Summary
Obstructive sleep apnoea syndrome (OSAS) disrupts clock gene function, specifically Period1 (Per1) mRNA expression. Continuous positive airway pressure (CPAP) therapy improved these disruptions, suggesting a link between sympathetic activation and circadian rhythm disorders in OSAS.
Area of Science:
- Chronobiology
- Sleep Medicine
- Molecular Biology
Background:
- Circadian rhythms are regulated by clock genes, and their dysfunction is linked to various health disorders.
- Obstructive sleep apnoea syndrome (OSAS) is a condition characterized by repeated episodes of upper airway collapse during sleep.
Purpose of the Study:
- To investigate the influence of obstructive sleep apnoea syndrome (OSAS) on clock gene function, specifically Period1 (Per1) mRNA expression.
- To determine the effect of continuous positive airway pressure (CPAP) therapy on Per1 mRNA expression in OSAS patients.
Main Methods:
- Measured plasma noradrenaline, serum interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and Per1 mRNA expression in peripheral blood of healthy subjects and OSAS patients.
- Examined Per1 mRNA expression in cultured cells stimulated with IL-6 or noradrenaline in vitro.
- Investigated Per1 mRNA expression in mouse brain after in vivo noradrenaline administration.
Main Results:
- OSAS patients exhibited elevated serum IL-6, hsCRP, and plasma noradrenaline, which improved with CPAP therapy.
- CPAP therapy significantly decreased Per1 mRNA expression at 02:00 h in OSAS patients' peripheral blood.
- In vitro IL-6 stimulation did not directly induce Per1 mRNA, but in vivo noradrenaline administration induced Per1 mRNA in the mouse cerebral cortex.
Conclusions:
- Obstructive sleep apnoea syndrome causes clock gene dysfunction, evidenced by altered Per1 mRNA expression.
- Continuous positive airway pressure therapy can help ameliorate these clock gene disruptions in OSAS.
- Sympathetic nervous system activation and elevated plasma noradrenaline in OSAS may contribute to Period1 mRNA expression disorders.
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