Serotonin impairment in CSF of PD patients, without an apparent clinical counterpart.
Serotonin impairment in CSF of PD patients, without an apparent clinical counterpart.
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DOI：
10.1371/journal.pone.0101763
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Stefani A
中科院分区：
文献类型：
--
作者：
Olivola E;Pierantozzi M;Imbriani P;Liguori C;Stampanoni Bassi M;Conti M;D'Angelo V;Mercuri NB;Stefani A
在帕金森氏病(PD)中，几项研究发现了5-羟色胺(5-HT)途径受损，可能同时影响运动和非运动领域。然而，5-羟色胺损伤的确切影响还远未确定。在这里，我们使用高效液相色谱方法，在无波动、无运动障碍的帕金森病患者的同质队列(n = 35)中，评估腰椎穿刺术(LP)获得的外周脑脊液中5-羟色胺及其代谢物5-羟色胺的浓度。在停药三天后进行LP，以消除长期释放的多巴胺激动剂(DA)的影响，并且在没有任何5-羟色胺能药物的情况下进行。与年龄匹配的对照组(n = 18人)或阿尔茨海默病患者(n = 20人)相比，PD患者组的脑脊液5-羟色胺和5-羟IAA水平均显著降低。而5-HT/5-HIAA水平与UPDRS-Ⅲ(r = −0.12)、病程(r = −0.1)、年龄(r = −0.27)和MMSE(r = 0.11)无相关性。有趣的是，低的脑脊液5-羟色胺水平没有性别或运动表型的差异(就非震颤显性亚型和震颤显性亚型而言)。此外，低水平的脑脊液5-羟色胺水平与抑郁、冷漠或睡眠障碍的存在无关。我们的发现支持5-羟色胺损伤是稳定性帕金森病的主要特征的观点，可能代表弥漫性路易体在脑干沉积的特征。然而，临床相关性仍然不确定。鉴于这些发现，在PD患者中使用5-羟色胺能药物的附加治疗似乎是有问题的，或者应该个体化治疗，除非存在严重的抑郁症。
In Parkinson's disease (PD), several studies have detected an impaired serotonin (5-HT) pathway, likely affecting both motor and non-motor domains. However, the precise impact of 5-HT impairment is far from established. Here, we have used a HPLC chromatographic method, in a homogenous cohort (n = 35) of non fluctuating, non dyskinetic PD patients, to assess the concentration of 5-HT and its metabolite 5-HIAA in peripheral cerebrospinal fluid (CSF) obtained from lumbar puncture (LP). LP was performed following three days of therapy withdrawal, in order to vanish the effects of prolonged released dopamine agonists (DA), and in absence of any serotonergic agent. The PD patient group showed a significantly reduced CSF level of both 5-HT and 5-HIAA compared to either age-matched control subjects (n = 18), or Alzheimer's disease patients (n = 20). However, no correlation emerged between 5-HT/5-HIAA concentrations and UPDRS-III (r = −0.12), disease duration (r = −0.1), age (r = −0.27) and MMSE (r = 0.11). Intriguingly, low CSF 5-HT levels did not differ for gender or for motor phenotype (in terms of non-tremor dominant subtype and tremor dominant subtype). Further, low CSF 5-HT levels did not correlate with the presence of depression, apathy or sleep disturbance. Our findings support the contention that 5-HT impairment is a cardinal feature of stable PD, probably representing a hallmark of diffuse Lewy bodies deposition in the brainstem. However, clinical relevance remains uncertain. Given these findings, an add-on therapy with serotonergic agents seems questionable in PD patients, or should be individually tailored, unless severe depression is present.
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影响因子：
48
作者：
Barone, Paolo;Poewe, Werner;Weintraub, Daniel
通讯作者：
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影响因子：
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作者：
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作者：
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作者：
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通讯作者：
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