Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson's Disease

PLoS One. 2016 Feb 22;11(2):e0149776. doi: 10.1371/journal.pone.0149776. eCollection 2016.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Callithrix
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Magnetic Resonance Imaging
  • Nerve Growth Factors / metabolism*
  • Oxidopamine / pharmacology
  • Parkinson Disease / metabolism*
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Oxidopamine

Grant support

EGR was funded by EU ERA-Net NEURON (PARKCDNF) (http://www.neuron-eranet.eu/). The study was partially supported by the DFG Research Center Molecular Physiology of the Brain (CMPB) (http://www.cmpb.uni-goettingen.de/) and by a S. Jusélius Foundation (http://www.sigridjuselius.fi/foundation) grant to MS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.