Circadian rhythm of CSF monoamines and hypocretin-1 in restless legs syndrome and Parkinson's disease.
Circadian rhythm of CSF monoamines and hypocretin-1 in restless legs syndrome and Parkinson's disease.
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DOI：
10.1016/j.sleep.2007.11.002
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发表时间：
2009
期刊：
影响因子：
4.8
通讯作者：
J. Poceta;L. Parsons;Scott Engelland;D. Kripke
中科院分区：
文献类型：
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作者：
J. Poceta;L. Parsons;Scott Engelland;D. Kripke
不宁腿综合征(RLS)的症状具有昼夜节律模式，中枢神经系统多巴胺参与了这种疾病的发病机制。我们试图描述人脑脊液中多巴胺和相关化合物的昼夜节律变化。从植入的腰椎硬膜内导管连续抽出脑脊液22h，采集3例RLS患者、3例帕金森病(PD)患者和3例健康志愿者的脑脊液。患者的疾病严重程度中等，不服用药物。采用反相高效液相色谱-电化学检测法，每隔30min测定脑脊液中的多巴胺(DA)、高香草酸(HVA)、二羟基苯乙酸(DOPAC)和5-羟基吲哚乙酸(5-HIAA)。用放射免疫法测定脑脊液中每小时一次的下丘脑肌素-1水平。这一过程是可以容忍的。一名患者因腰椎神经根疼痛而提前结束研究，未被纳入分析。从第一个样本到最后一个样本，脑脊液细胞计数或蛋白质水平没有变化。不同组之间的任何化合物都没有差异，所以我们用24小时余弦来检验整个组是否具有显著的相一致性。多巴胺的峰值出现在上午10点。(P<；0.025)和下午2点的HVA(P<；0.01)，但没有证据表明DOPAC、5-HIAA、HVA/5-HIAA比值或下丘脑-1存在显著的24小时节律。这些结果表明，人类脑脊液中的多巴胺和HVA浓度存在昼夜节律，白天的浓度高于夜间。这种昼夜节律变化可能是帕金森病患者RLS症状和睡眠相关运动功能变化的基础。
The symptoms of restless legs syndrome (RLS) have a circadian pattern and central nervous system dopamine has been implicated in the pathogenesis of the condition. We sought to characterize circadian variation in dopamine and related compounds in human cerebro-spinal fluid (CSF). CSF was continuously withdrawn for 22h from an implanted lumbar intradural catheter and sampled from three patients with RLS, three patients with Parkinson’s disease (PD) and three healthy volunteers. Patients had moderate disease severity and took no medications. We assayed CSF dopamine (DA), homovanillic acid (HVA), dihydroxy-phenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) from samples every 30min by reversed-phase HPLC coupled with electrochemical detection. We also measured CSF levels of hypocretin-1 every hour by RIA. The procedure was well-tolerated. One patient ended the study early due to lumbar radicular pain and was not included in the analysis. There were no changes in CSF cell counts or protein levels from the first to the last samples. There was no difference in any of the compounds between groups, so we fit 24-h cosines to examine if the entire group had significant phase consistency. There was a peak for dopamine at 10 a.m. (p<0.025) and for HVA at 2 p.m. (p<0.01), but no evidence of a significant 24-h rhythm for DOPAC, 5-HIAA, the HVA/5-HIAA ratio, or hypocretin-1. These results demonstrate a circadian rhythm for CSF dopamine and HVA concentrations in humans, with higher levels in the daytime than at nighttime. This circadian variation could underlie the symptoms of RLS and sleep-related variation in motor function in PD.