Department of Philosophical and Methodological Disciplines, University Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
Department of Philosophical and Methodological Disciplines, University Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico; Division of Neurosciences, Western Biomedical Research Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico.
Biomed Pharmacother. 2020 Sep;129:110485. doi: 10.1016/j.biopha.2020.110485. Epub 2020 Jul 6.
Sleep disorders are a widespread condition in patients with Parkinson's disease (PD), which has been linked to a deregulation of the circadian cycle and therefore of the clock genes. The aim of this study was to evaluate the effect of melatonin (MEL) on the PER1 and BMAL1 clock genes in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial pilot study was conducted in 26 patients with stage 1-3 PD according to the Hoehn & Yahr scale, who received either 25 mg of MEL or a placebo at noon and 30 min before bedtime for three months. The relative expression of the PER1 and BMAL1 genes was measured, as well as the presence of daytime, nocturnal, and global sleepiness, and the progression of PD. The levels of the PER1 and BMAL1 genes at baseline were 0.9 (0.1-3) vs. 0.56 (0.1-2.5), respectively; while after the intervention with MEL or placebo the BMAL1 levels increased to 2.5 (0-3.70) vs. 2.2 (0.10-3.30), respectively (d = 0.387). Fifty percent (50 %) of patients had daytime sleepiness and sixty-five percent (65 %) had abnormal nighttime sleepiness, yet neither group showed changes after the intervention. Patients with PD exhibited an alteration in the levels of the clock genes: MEL increased the levels of BMAL1, but the PER1 levels remained unchanged.
睡眠障碍是帕金森病（PD）患者的一种普遍病症，其与昼夜节律周期的失调有关，进而导致时钟基因的失调。本研究旨在评估褪黑素（MEL）对 PD 患者 PER1 和 BMAL1 时钟基因的影响。一项双盲、交叉、安慰剂对照的随机临床试验试点研究纳入了 26 名根据 Hoehn 和 Yahr 量表处于 1-3 期的 PD 患者，他们在中午和睡前 30 分钟分别接受 25 毫克 MEL 或安慰剂治疗，为期三个月。测量了 PER1 和 BMAL1 基因的相对表达水平，以及日间、夜间和整体嗜睡的存在情况，以及 PD 的进展情况。PER1 和 BMAL1 基因的基线水平分别为 0.9（0.1-3）和 0.56（0.1-2.5）；而在接受 MEL 或安慰剂干预后，BMAL1 水平分别增加到 2.5（0-3.70）和 2.2（0.10-3.30）（d = 0.387）。50%的患者有日间嗜睡，65%的患者有夜间睡眠异常，但两组在干预后均未显示出变化。PD 患者的时钟基因水平发生了改变：MEL 增加了 BMAL1 的水平，但 PER1 水平保持不变。
