Department of Physiology, Federal University of Paraná, Curitiba, PR, Brazil.
Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
Sci Rep. 2019 Feb 13;9(1):1898. doi: 10.1038/s41598-018-37657-6.
Parkinson's disease (PD) is a chronic disorder that presents a range of premotor signs, such as sleep disturbances and cognitive decline, which are key non-motor features of the disease. Increasing evidence of a possible association between sleep disruption and the neurodegenerative process suggests that sleep impairment could produce a detectable metabolic signature on the disease. In order to integrate neurocognitive and metabolic parameters, we performed untargeted and targeted metabolic profiling of the rotenone PD model in a chronic sleep restriction (SR) (6 h/day for 21 days) condition. We found that SR combined with PD altered several behavioural (reversal of locomotor activity impairment; cognitive impairment; delay of rest-activity rhythm) and metabolic parameters (branched-chain amino acids, tryptophan pathway, phenylalanine, and lipoproteins, pointing to mitochondrial impairment). If combined, our results bring a plethora of parameters that represents reliable early-phase PD biomarkers which can easily be measured and could be translated to human studies.
帕金森病（PD）是一种慢性疾病，表现出一系列运动前期迹象，如睡眠障碍和认知能力下降，这些都是该疾病的关键非运动特征。越来越多的证据表明，睡眠中断与神经退行性过程之间可能存在关联，这表明睡眠障碍可能会在疾病中产生可检测的代谢特征。为了整合神经认知和代谢参数，我们在慢性睡眠限制（SR）（每天 6 小时，持续 21 天）条件下对鱼藤酮 PD 模型进行了非靶向和靶向代谢谱分析。我们发现，SR 与 PD 相结合改变了几种行为（运动活动损伤的逆转；认知损伤；休息-活动节律延迟）和代谢参数（支链氨基酸、色氨酸途径、苯丙氨酸和脂蛋白，提示线粒体损伤）。如果结合起来，我们的结果带来了大量的参数，这些参数代表了可靠的早期 PD 生物标志物，这些标志物可以很容易地测量，并可转化为人类研究。
