AUTHOR=Li Tianbai , Cheng Cheng , Jia Congcong , Leng Yue , Qian Jin , Yu Hang , Liu Yufei , Wang Nanxing , Yang Yuting , Al-Nusaif Murad , Le Weidong 

TITLE=Peripheral Clock System Abnormalities in Patients With Parkinson’s Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.736026

DOI=10.3389/fnagi.2021.736026

ISSN=1663-4365

ABSTRACT=<p><bold>Objective:</bold> 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.</p><p><bold>Methods:</bold> We determined the expression profiles of five principal clock genes, <italic>BMAL1</italic>, <italic>CLOCK</italic>, <italic>CRY1</italic>, <italic>PER1</italic>, and <italic>PER2</italic>, in the peripheral blood mononuclear cells (PBMCs) of PD patients (<italic>n</italic> = 326), and healthy controls (HC, <italic>n</italic> = 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.</p><p><bold>Results:</bold> Our data showed that the expression levels of <italic>BMAL1</italic>, <italic>CLOCK</italic>, <italic>CRY1</italic>, <italic>PER1</italic>, and <italic>PER2</italic> were significantly decreased in the PBMCs of PD as compared with that of HC (<italic>P</italic> &lt; 0.05). PD patients had reduced plasma melatonin levels compared with HC (<italic>P</italic> &lt; 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 (<italic>r</italic> = −0.344∼−0.789, <italic>P</italic> &lt; 0.01) and melatonin concentration (<italic>r</italic> = −0.509∼−0.753, <italic>P</italic> &lt; 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.</p><p><bold>Conclusion:</bold> This case-control study demonstrates that peripheral <italic>BMAL1</italic>, <italic>CLOCK</italic>, <italic>CRY1</italic>, <italic>PER1, PER2</italic>, and melatonin levels are altered in PD patients and may serve as endogenous markers for sleep and wakefulness disturbances of PD.</p>