Peripheral Clock System Abnormalities in Patients With Parkinson’s Disease

Frontiers in Aging Neuroscience

Jin Qian¹  Murad Al-Nusaif³  Yufei Liu³  Tianbai Li³  Yuting Yang³  Congcong Jia³  Cheng Cheng³  Nanxing Wang³  Yue Leng⁴  Hang Yu⁵  Weidong Le⁵ 

[1]Department of Neurology, The First Affiliated Hospital, Dalian Medical University, Dalian, China

[2]Department of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States

[3]Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China

[4]San Francisco VA Medical Center, San Francisco, CA, United States

[5]Sichuan Provincial Hospital, Institute of Neurology, Sichuan Academy of Medical Sciences, Chengdu, China

关键词: clock gene;    melatonin;    Parkinson’s disease;    circadian rhythm;    sleep-wake disturbances;   

DOI  :  10.3389/fnagi.2021.736026

来源: DOAJ

【 摘 要 】

Objective: To evaluate the altered expression of peripheral clock genes, circulating melatonin levels, and their correlations with sleep-wake phenotypes including probable rapid eye movement sleep behavior disorder (pRBD) symptoms in a relatively large population of Parkinson’s disease (PD) patients.Methods: We determined the expression profiles of five principal clock genes, BMAL1, CLOCK, CRY1, PER1, and PER2, in the peripheral blood mononuclear cells (PBMCs) of PD patients (n = 326), and healthy controls (HC, n = 314) using quantitative real-time PCR. Melatonin concentration in the plasma of two groups was evaluated by enzyme-linked immunosorbent assay. Then we performed comprehensive association analyses on the PBMCs clock gene expression, plasma melatonin levels and sleep characteristics.Results: Our data showed that the expression levels of BMAL1, CLOCK, CRY1, PER1, and PER2 were significantly decreased in the PBMCs of PD as compared with that of HC (P < 0.05). PD patients had reduced plasma melatonin levels compared with HC (P < 0.0001). pRBD and excessive daytime sleepiness are common in these PD patients and are associated with the expression levels of all five clock genes (r = −0.344∼−0.789, P < 0.01) and melatonin concentration (r = −0.509∼−0.753, P < 0.01). Statistical analyses also revealed that a combination of five clock genes and melatonin could reach a high diagnostic performance (areas under the curves, 97%) for PD comorbid pRBD.Conclusion: This case-control study demonstrates that peripheral BMAL1, CLOCK, CRY1, PER1, PER2, and melatonin levels are altered in PD patients and may serve as endogenous markers for sleep and wakefulness disturbances of PD.

【 授权许可】

Unknown