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Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic REM sleep behavior disorder
Institution:1. National Institute of Mental Health, Klecany, Czech Republic;2. Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic;3. Department of Neurology and Centre of Clinical Neurosciences, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic;4. Third Faculty of Medicine, Charles University, Prague, Czech Republic
Abstract:ObjectiveTo evaluate changes in the expression of clock genes and melatonin levels in patients with idiopathic REM sleep behavior disorder (RBD) as a potential early stage of synucleinopathies.MethodsWe assessed the rhythmicity of circadian clock genes using real time-quantitative polymerase chain reaction and 24-h blood melatonin profiles using radio-immunoassay in 10 RBD patients and nine age-matched controls.ResultsThe RBD patients did not show circadian rhythmicity for clock genes Per2, Bmal1, and Nr1d1 but the rhythmicity of Per 1 remained, and the amplitude of Per3 was diminished. The 24-h melatonin rhythm did not differ between RBD patients and healthy control subjects. Melatonin profile in RBD patients was delayed by 2 h compared to controls, the habitual sleep phases were phase delayed by about 1 h, however no phase shift occurred in any of the clock genes studied. The control group had stable acrophases of melatonin rhythms of approximately 5 h whereas the RBD patients had a more dispersed range over 11 h.ConclusionsOur results suggest that RBD could be associated with altered expression of clock genes and delayed melatonin secretion. Thus, we argue that circadian system dysregulation could play a role in RBD.
Keywords:Idiopathic rapid eye movement sleep (REM) sleep behavior disorder  Clock genes expression  Melatonin
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