Increased Serum Levels of Mesencephalic Astrocyte-Derived Neurotrophic Factor in Subjects With Parkinson's Disease
Increased Serum Levels of Mesencephalic Astrocyte-Derived Neurotrophic Factor in Subjects With Parkinson's Disease
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DOI：
10.3389/fnins.2019.00929
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发表时间：
2019-09-04
影响因子：
4.3
通讯作者：
Lindholm, Paivi
中科院分区：
文献类型：
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作者：
Galli, Emilia;Planken, Anu;Lindholm, Paivi
背景：中脑星形细胞源性神经营养因子（MANF）和脑多巴胺神经营养因子（CDNF）可促进帕金森病（PD）动物模型中脑多巴胺神经元的存活。然而，关于人PD患者体内的内源性MANF和CDNF浓度及其与PD发病机制的关系，我们知之甚少。我们的主要目的是研究PD患者和对照组之间循环中MANF和CDNF浓度是否存在差异，以及它们是否与临床参数相关。首次对循环CDNF水平进行了研究。方法：采用实验室设计的酶联免疫吸附法（elisa）检测34例PD患者和35例对照者血清样本中的MANF和CDNF水平。采用定量实时聚合酶链反应（qRT-PCR）技术检测60例PD患者和30例对照者全血中MANF和CDNF mRNA水平。采用酶联免疫吸附法测定不同类型血细胞中MANF的浓度。结果：PD患者循环MANF浓度显著高于对照组（P < 0.001），且与贝克抑郁量表（BDI）抑郁评分呈正相关。血细胞中存在MANF蛋白，但PD患者和对照组血液中MANF mRNA水平无差异（P = 0.44）。对照组血清CDNF平均浓度为33 pg/ml。PD患者的CDNF水平未发生改变（P = 0.25）。结论：PD患者血液中MANF水平升高，CDNF水平不升高。在未来的研究中，检测早期PD患者血液中MANF的水平，以检验MANF是否可以作为PD的临床标志物，是值得关注的。
Background: Mesencephalic astrocyte-derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) promote the survival of midbrain dopamine neurons in animal models of Parkinson's disease (PD). However, little is known about endogenous concentrations of MANF and CDNF in human PD patients, and their relation to PD pathogenesis. Our main objective was to study whether circulating concentrations of MANF and CDNF differ between PD patients and controls, and if they correlate with clinical parameters. Levels of circulating CDNF were studied for the first time.Methods: MANF and CDNF levels were measured from serum samples of 34 PD patients and 35 controls using validated in-lab-designed enzyme-linked immunosorbent assay (ELISAs). MANF and CDNF mRNA levels in whole blood samples of 60 PD patients and 30 controls were measured by quantitative real time polymerase chain reaction (qRT-PCR). MANF concentrations in different blood cell types were measured by ELISA.Results: Circulating MANF concentrations were significantly higher in PD patients compared to controls (P < 0.001) and were positively correlated with Beck Depression Inventory (BDI) depression rating. MANF protein was present in blood cells, however, MANF mRNA levels in the blood did not differ between PD patients and controls (P = 0.44). The mean concentration of serum CDNF was 33 pg/ml in the controls. CDNF levels were not altered in PD patients (P = 0.25).Conclusion: MANF but not CDNF level was increased in the blood of PD patients. It would be interesting to examine the blood level of MANF from early stage PD patients in future studies to test whether MANF can be used as a clinical marker of PD.