Expression of clock genes Per1 and Bmal1 in total leukocytes in health and Parkinson's disease.
BACKGROUND
There is a growing number of clinical studies that revealed a variety of behavioral and physiological desynchronies in patients with Parkinson's disease (PD). However, these desynchronies have not been defined at the molecular level.


METHODS
Using real-time RT-PCR assay, we analyzed the expression profiles of two principle clock genes, PER1 and BMAL1, in total leukocytes for 12 h during the evening, overnight and morning in subjects with PD and age/sex-matched healthy controls.


RESULTS
A difference in the expression pattern of BMAL1 but not PER1 was apparent during the dark span, where the relative abundance of BMAL1 was significantly lower in PD patients versus control subjects at 21:00, 00:00 and 06:00 h. Furthermore, expression levels of BMAL1 in PD patients correlated with their United Parkinson's Disease Rating Scale score at 06:00, 09:00 h, and with Pittsburgh Sleep Quality Index score at 06:00 h.


CONCLUSIONS
These results suggest that a peripheral molecular clock, as reflected in the dampened expression of the clock genes BMAL1 in total leukocytes, is altered in PD patients. In addition, the relative BMAL1 levels correlate positively with PD severity, which could provide a molecular basis to help monitor disease progression and response to investigational drugs.
Cai
Y
Y
Department of Neurology and Neurobiology, Capital Medical University, Key Laboratory of Neurodegenerative Diseases Capital Medical University, Ministry of Education, Beijing, China.
Liu
S
S
Sothern
R B
RB
Xu
S
S
Chan
P
P
D056930:ARNTL Transcription Factors / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000502:physiology; D003624:Darkness; D005260:Female; D006304:Health Status; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D056950:Period Circadian Proteins / Q000097:blood / Q000378:metabolism*; D017440:Photoperiod; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D013997:Time Factors
D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; C539022:PER1 protein, human; D056950:Period Circadian Proteins; D012333:RNA, Messenger