TY - JOUR
T1 - Peripheral Clock System Abnormalities in Patients With Parkinson’s Disease
AU - Li, Tianbai
AU - Cheng, Cheng
AU - Jia, Congcong
AU - Leng, Yue
AU - Qian, Jin
AU - Yu, Hang
AU - Liu, Yufei
AU - Wang, Nanxing
AU - Yang, Yuting
AU - Al-Nusaif, Murad
AU - Le, Weidong
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (NSFC 81771521 and 82001483), the National Key R&D Program (2016YFC1306600), and the Guangdong Provincial Key R&D Program (2018B030337001).
Publisher Copyright:
© Copyright © 2021 Li, Cheng, Jia, Leng, Qian, Yu, Liu, Wang, Yang, Al-Nusaif and Le.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
KW - Parkinson’s disease
KW - circadian rhythm
KW - clock gene
KW - melatonin
KW - sleep-wake disturbances
UR - http://www.scopus.com/inward/record.url?scp=85117195029&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85117195029&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2021.736026
DO - 10.3389/fnagi.2021.736026
M3 - Article
AN - SCOPUS:85117195029
VL - 13
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
M1 - 736026
ER -