Kostovski Emil, Frigato Elena, Savikj Mladen, Dahm Anders, Sandset Per Morten, Mowinckel Marie-Christine, Skretting Grethe, Østerud Bjarne, Bertolucci Cristiano, Iversen Per Ole
Department of Research, Sunnaas Rehabilitation Hospital, Nesoddtangen, Norway.
Faculty of Medicine, University of Oslo, Oslo, Norway.
Spinal Cord. 2018 Nov;56(11):1076-1083. doi: 10.1038/s41393-018-0176-x. Epub 2018 Jul 9.
Crossover double blind, randomized placebo-controlled trial.
Circadian oscillators are located both in the brain and in peripheral organs. Melatonin, the main brain-derived hormone governing circadian variations, is highly associated with daylight patterns. However, in subjects with tetraplegia the melatonin levels are blunted. Here we studied peripheral oscillators in peripheral blood mononuclear cells (PBMCs) in males with tetraplegia by examining how exogenous melatonin may influence the expression of clock gene mRNAs.
Sunnaas Rehabilitation Hospital, Nesoddtangen, Norway.
Six males with tetraplegia received 2 mg of melatonin or placebo 4 days before the study period. We also included six able-bodied men sleeping or kept awake during the night. Plasma samples were collected four times during a 24-h period. The mRNA expression levels of the clock genes PER1, PER2, BMAL1, and REV-ERBα were quantified in PBMCs using quantitative RT-PCR.
The mRNA expression levels of PER-1 and -2 and REV-ERBα were increased at 04:00 h compared with the able-bodied controls (p < 0.05). Melatonin supplementation changed mRNA peak-time toward the time of supplementation.
Several peripheral clock genes displayed distorted expression levels in tetraplegia. Supplementation with melatonin changed the mRNA expression levels of these genes toward those observed among able-bodied.
Financial support was provided from the Throne Holst Foundation, Sunnaas Rehabilitation hospital and the University of Ferrara (FAR2016).
交叉双盲随机安慰剂对照试验。
昼夜节律振荡器位于大脑和外周器官中。褪黑素是主要由大脑产生的调节昼夜节律变化的激素，与日光模式高度相关。然而，在四肢瘫痪患者中，褪黑素水平会降低。在此，我们通过研究外源性褪黑素如何影响时钟基因mRNA的表达，来研究四肢瘫痪男性外周血单核细胞（PBMC）中的外周振荡器。
挪威内索登滕的松纳斯康复医院。
6名四肢瘫痪男性在研究期前4天接受2毫克褪黑素或安慰剂。我们还纳入了6名夜间睡眠或保持清醒的健康男性。在24小时内分4次采集血浆样本。使用定量逆转录聚合酶链反应（qRT-PCR）对PBMC中时钟基因PER1、PER2、BMAL1和REV-ERBα的mRNA表达水平进行定量。
与健康对照相比，PER-1、PER-2和REV-ERBα的mRNA表达水平在04:00时升高（p < 0.05）。补充褪黑素使mRNA峰值时间朝着补充时间变化。
在四肢瘫痪患者中，几种外周时钟基因的表达水平出现扭曲。补充褪黑素使这些基因的mRNA表达水平向健康人观察到的水平变化。
由托恩·霍尔斯特基金会、松纳斯康复医院和费拉拉大学（FAR2016）提供资金支持。
