Expression of clock genes Per1 and Bmal1 in total leukocytes in health and Parkinson's disease
Expression of clock genes Per1 and Bmal1 in total leukocytes in health and Parkinson's disease
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DOI：
10.1111/j.1468-1331.2009.02848.x
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发表时间：
2010-04-01
影响因子：
5.1
通讯作者：
Chan, P.
中科院分区：
文献类型：
--
作者：
Cai, Y.;Liu, S.;Chan, P.
背景：越来越多的临床研究显示帕金森病（PD）患者存在多种行为和生理障碍。然而，这些desperies尚未被定义在molecular level.Methods：使用实时RT-PCR检测，我们分析了两个主要的时钟基因，PER 1和BMAL 1，在总白细胞的表达谱为12小时，在晚上，过夜和早晨在PD和年龄/性别匹配的健康controls.Results：在BMAL 1的表达模式的差异，但不是PER 1是明显的，在黑暗的跨度，其中BMAL 1的相对丰度在PD患者与对照受试者在21：00，00：00和06：00小时。此外，BMAL 1在PD患者的表达水平与他们的联合帕金森氏病评定量表评分在06：00，09：00小时，并与匹兹堡睡眠质量指数评分在06：00小时。结论：这些结果表明，外周分子时钟，反映在总白细胞中的时钟基因BMAL 1的表达抑制，在PD患者中改变。此外，BMAL 1的相对水平与PD严重程度呈正相关，这可以为帮助监测疾病进展和对研究药物的反应提供分子基础。
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.Conclusion: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.