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特发性 REM 睡眠行为障碍患者褪黑素和外周时钟基因表达的昼夜节律。

Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic REM sleep behavior disorder.

机构信息

National Institute of Mental Health, Klecany, Czech Republic; Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic.

Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic.

出版信息

Sleep Med. 2018 Dec;52:1-6. doi: 10.1016/j.sleep.2018.07.019. Epub 2018 Aug 9.

Abstract

OBJECTIVE

To 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.

METHODS

We 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.

RESULTS

The 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.

CONCLUSIONS

Our 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.

摘要

目的

评估特发性快速眼动睡眠行为障碍(RBD)患者时钟基因表达和褪黑素水平的变化,作为神经突触核蛋白病的早期阶段。

方法

我们使用实时定量聚合酶链反应评估了 10 名 RBD 患者和 9 名年龄匹配的对照者的时钟基因节律性,使用放射免疫分析评估了 24 小时褪黑素水平。

结果

RBD 患者的时钟基因 Per2、Bmal1 和 Nr1d1 没有表现出昼夜节律性,但 Per 1 的节律性仍然存在,Per3 的振幅降低。RBD 患者和健康对照组之间的 24 小时褪黑素节律没有差异。与对照组相比,RBD 患者的褪黑素曲线延迟了 2 小时,习惯性睡眠阶段延迟了约 1 小时,但在研究的任何时钟基因中都没有发生相位变化。对照组的褪黑素节律约有 5 小时的稳定峰值,而 RBD 患者的峰值范围则分散在 11 小时左右。

结论

我们的结果表明,RBD 可能与时钟基因表达的改变和褪黑素分泌的延迟有关。因此,我们认为昼夜节律系统失调可能在 RBD 中起作用。

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