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

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

Author information

1
Clinical Neurobiology Laboratory, German Primate Center, Göttingen, Germany.
2
Department of Neuroanatomy Institute of Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
3
Center for Molecular Physiology of the Brain (CMPB), University of Göttingen, Göttingen, Germany.
4
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
5
Encepharm, Göttingen, Germany.
6
Department of Nuclear Medicine, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
7
Department of Molecular Embryology, Institute for Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
8
Department of Cognitive Neurology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.

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.

PMID:
26901822
PMCID:
PMC4763937
DOI:
10.1371/journal.pone.0149776
[Indexed for MEDLINE]
Free PMC Article

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