Garea-Rodríguez Enrique, Eesmaa Ave, Lindholm Päivi, Schlumbohm Christina, König Jessica, Meller Birgit, Krieglstein Kerstin, Helms Gunther, Saarma Mart, Fuchs Eberhard
Clinical Neurobiology Laboratory, German Primate Center, Göttingen, Germany.
Department of Neuroanatomy Institute of Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
PLoS One. 2016 Feb 22;11(2):e0149776. doi: 10.1371/journal.pone.0149776. eCollection 2016.
Cerebral dopamine neurotrophic factor (CDNF) belongs to a newly discovered family of evolutionarily conserved neurotrophic factors. We demonstrate for the first time a therapeutic effect of CDNF in a unilateral 6-hydroxydopamine (6-OHDA) lesion model of Parkinson's disease in marmoset monkeys. Furthermore, we tested the impact of high chronic doses of human recombinant CDNF on unlesioned monkeys and analyzed the amino acid sequence of marmoset CDNF. The severity of 6-OHDA lesions and treatment effects were monitored in vivo using 123I-FP-CIT (DaTSCAN) SPECT. Quantitative analysis of 123I-FP-CIT SPECT showed a significant increase of dopamine transporter binding activity in lesioned animals treated with CDNF. Glial cell line-derived neurotrophic factor (GDNF), a well-characterized and potent neurotrophic factor for dopamine neurons, served as a control in a parallel comparison with CDNF. By contrast with CDNF, only single animals responded to the treatment with GDNF, but no statistical difference was observed in the GDNF group. However, increased numbers of tyrosine hydroxylase immunoreactive neurons, observed within the lesioned caudate nucleus of GDNF-treated animals, indicate a strong bioactive potential of GDNF.
脑源性多巴胺神经营养因子（CDNF）属于新发现的一个进化上保守的神经营养因子家族。我们首次在狨猴帕金森病单侧6-羟基多巴胺（6-OHDA）损伤模型中证实了CDNF的治疗效果。此外，我们测试了高剂量慢性给予人重组CDNF对未损伤狨猴的影响，并分析了狨猴CDNF的氨基酸序列。使用123I-FP-CIT（DaTSCAN）SPECT在体内监测6-OHDA损伤的严重程度和治疗效果。123I-FP-CIT SPECT的定量分析显示，接受CDNF治疗的损伤动物中多巴胺转运体结合活性显著增加。胶质细胞源性神经营养因子（GDNF）是一种已得到充分研究且对多巴胺神经元有效的神经营养因子，在与CDNF的平行比较中用作对照。与CDNF不同，只有单只动物对GDNF治疗有反应，但GDNF组未观察到统计学差异。然而，在接受GDNF治疗的动物损伤尾状核内观察到酪氨酸羟化酶免疫反应性神经元数量增加，这表明GDNF具有强大的生物活性潜力。
