Galli Emilia, Planken Anu, Kadastik-Eerme Liis, Saarma Mart, Taba Pille, Lindholm Päivi
Institute of Biotechnology, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
North Estonia Medical Centre Foundation, Tallinn, Estonia.
Front Neurosci. 2019 Sep 4;13:929. doi: 10.3389/fnins.2019.00929. eCollection 2019.
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.
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). and 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.
Circulating MANF concentrations were significantly higher in PD patients compared to controls ( < 0.001) and were positively correlated with Beck Depression Inventory (BDI) depression rating. MANF protein was present in blood cells, however, mRNA levels in the blood did not differ between PD patients and controls ( = 0.44). The mean concentration of serum CDNF was 33 pg/ml in the controls. CDNF levels were not altered in PD patients ( = 0.25).
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.
中脑星形胶质细胞源性神经营养因子（MANF）和脑源性多巴胺神经营养因子（CDNF）在帕金森病（PD）动物模型中可促进中脑多巴胺能神经元的存活。然而，对于人类PD患者体内MANF和CDNF的内源性浓度及其与PD发病机制的关系知之甚少。我们的主要目的是研究PD患者与对照组之间MANF和CDNF的循环浓度是否存在差异，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。
使用经过验证的实验室自行设计的酶联免疫吸附测定（ELISA）法，检测34例PD患者和35例对照者血清样本中MANF和CDNF的水平。通过定量实时聚合酶链反应（qRT-PCR）检测60例PD患者和30例对照者全血样本中的 和 mRNA水平。采用ELISA法检测不同血细胞类型中的MANF浓度。
与对照组相比，PD患者的循环MANF浓度显著升高（ < 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，然而，PD患者与对照组血液中的 mRNA水平无差异（ = 0.44）。对照组血清CDNF的平均浓度为33 pg/ml。PD患者的CDNF水平未发生改变（ = 0.25）。
PD患者血液中MANF水平升高，而CDNF水平未升高。未来研究检测早期PD患者血液中MANF水平，以检验MANF是否可作为PD的临床标志物，将是很有意义的。
