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特发性嗜睡症患者外周皮肤成纤维细胞的昼夜节律周期更长。

Idiopathic Hypersomnia Patients Revealed Longer Circadian Period Length in Peripheral Skin Fibroblasts.

作者信息

Materna Linus, Halfter Hartmut, Heidbreder Anna, Boentert Matthias, Lippert Julian, Koch Raphael, Young Peter

机构信息

Division of Sleep Medicine and Neuromuscular Disorders, Department of Neurology, University Hospital Muenster, Muenster, Germany.

Department of Neurology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland.

出版信息

Front Neurol. 2018 Jun 7;9:424. doi: 10.3389/fneur.2018.00424. eCollection 2018.

Abstract

The vast majority of living organisms have evolved a circadian rhythm of roughly 24 h in adaptation to ever-changing environmental conditions, such as the cycle of light and darkness. In some sleep disorders like idiopathic hypersomnia (IH) this adaptation is defective. As the etiology of this disease is largely unknown, we examined the circadian period length of patients suffering from IH. The patients were diagnosed according to the ICSD3-criteria by clinical history, polysomnography (PSG), and multiple sleep latency testing (MSLT). In order to gain insight into the molecular mechanism of this sleep disorder we collected fibroblasts from skin biopsies of IH patients and healthy subjects. We determined the circadian period length of the primary fibroblast cells by lentiviral infection with a construct expressing a luciferase gene under the control of a promoter. The group of IH patients revealed on average a prolonged circadian period length. In comparison to the group of healthy controls (HC) the mean period length was estimated to be 0.82 h (95%-CI 0.44-1.20 h) longer in the patient group. This finding further stresses a disturbed regulation of the circadian rhythm in IH patients as part of the pathophysiology of this complex and poorly understood primary sleep disorder.

摘要

绝大多数生物进化出了大约24小时的昼夜节律,以适应不断变化的环境条件,如昼夜循环。在一些睡眠障碍中,如特发性嗜睡症(IH),这种适应性存在缺陷。由于这种疾病的病因在很大程度上尚不清楚,我们研究了IH患者的昼夜周期长度。根据ICSD3标准,通过临床病史、多导睡眠图(PSG)和多次睡眠潜伏期测试(MSLT)对患者进行诊断。为了深入了解这种睡眠障碍的分子机制,我们从IH患者和健康受试者的皮肤活检中收集成纤维细胞。我们通过用在启动子控制下表达荧光素酶基因的构建体进行慢病毒感染,测定原代成纤维细胞的昼夜周期长度。IH患者组平均昼夜周期长度延长。与健康对照组(HC)相比,患者组的平均周期长度估计长0.82小时(95%置信区间0.44-1.20小时)。这一发现进一步强调了IH患者昼夜节律调节紊乱是这种复杂且了解甚少的原发性睡眠障碍病理生理学的一部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85f4/5999733/673d62e617ee/fneur-09-00424-g0001.jpg

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