Peripheral Dopamine in Restless Legs Syndrome.

Peripheral Dopamine in Restless Legs Syndrome.
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DOI:
10.3389/fneur.2018.00155
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发表时间:
2018
影响因子:
3.4
通讯作者:
Steffensen SC
Steffensen SC
中科院分区:
医学3区
文献类型:
--
作者:
Mitchell UH;Obray JD;Hunsaker E;Garcia BT;Clarke TJ;Hope S;Steffensen SC

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不宁腿综合症(RLS)是一种以强烈的运动冲动为特征的多巴胺依赖型疾病。本研究的目的是评估RLS患者血中多巴胺和其他儿茶酚胺水平以及血中D2亚型多巴胺受体(D2Rs)水平。用高效液相色谱法检测年龄匹配的非用药RLS患者、用药RLS患者和对照组血液中的多巴胺水平,并用荧光激活细胞分选和免疫细胞化学法检测D2R白细胞(WBC)多巴胺D2R表达水平。服用药物的RLS受试者与未服药的RLS受试者和对照组相比,血浆多巴胺水平显著升高,但去甲肾上腺素或肾上腺素水平未见显著升高。对照组、RLS干预组和RLS非干预组的淋巴细胞和单核细胞表达D2Rs的百分率不同。在对照组、RLS用药组和RLS非用药组之间,淋巴细胞中总D2R的表达不同,但单核细胞中D2R的表达不同。对照组淋巴细胞中的D2Rs仅对多巴胺敏感,而单核细胞中的D2Rs则不敏感。WBC D2Rs的下调发生在RLS中。这种下调并不能被药物逆转,尽管常用的RLS药物会提高血浆多巴胺水平。单核细胞对多巴胺水平的不敏感,但它们在RLS中的下调,可能反映了它们作为RLS的生物标志物的效用,或许还反映了脑多巴胺的动态平衡。
Restless Legs Syndrome (RLS) is a dopamine-dependent disorder characterized by a strong urge to move. The objective of this study was to evalulate blood levels of dopamine and other catecholamines and blood D2-subtype dopamine receptors (D2Rs) in RLS. Dopamine levels in blood samples from age-matched unmedicated RLS subjects, medicated RLS subjects and Controls were evaluated with high performance liquid chromatography and dopamine D2R white blood cell (WBC) expression levels were determined with fluorescence-activated cell sorting and immunocytochemistry. Blood plasma dopamine levels, but not norepinepherine or epinephrine levels, were significantly increased in medicated RLS subjects vs unmedicated RLS subjects and Controls. The percentage of lymphocytes and monocytes expressing D2Rs differed between Control, RLS medicated and RLS unmedicated subjects. Total D2R expression in lymphocytes, but not monocytes, differed between Control, RLS medicated and RLS unmedicated subjects. D2Rs in lymphocytes, but not monocytes, were sensitive to dopamine in Controls only. Downregulation of WBCs D2Rs occurs in RLS. This downregulation is not reversed by medication, although commonly used RLS medications increase plasma dopamine levels. The insensitivity of monocytes to dopamine levels, but their downregulation in RLS, may reflect their utility as a biomarker for RLS and perhaps brain dopamine homeostasis.
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