title: Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson's Disease.
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.
authors.affiliation: Clinical Neurobiology Laboratory, German Primate Center, Göttingen, Germany.|Department of Neuroanatomy Institute of Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany.|Center for Molecular Physiology of the Brain (CMPB), University of Göttingen, Göttingen, Germany.
authors.forename: Enrique
authors.initials: E
authors.lastname: Garea-Rodríguez
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Ave
authors.initials: A
authors.lastname: Eesmaa
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Lindholm
authors.affiliation: Clinical Neurobiology Laboratory, German Primate Center, Göttingen, Germany.|Encepharm, Göttingen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Schlumbohm
authors.affiliation: Clinical Neurobiology Laboratory, German Primate Center, Göttingen, Germany.|Encepharm, Göttingen, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: König
authors.affiliation: Department of Nuclear Medicine, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Meller
authors.affiliation: Department of Molecular Embryology, Institute for Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Krieglstein
authors.affiliation: Department of Cognitive Neurology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Gunther
authors.initials: G
authors.lastname: Helms
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Mart
authors.initials: M
authors.lastname: Saarma
authors.affiliation: Clinical Neurobiology Laboratory, German Primate Center, Göttingen, Germany.|Center for Molecular Physiology of the Brain (CMPB), University of Göttingen, Göttingen, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D002144:Callithrix; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009414:Nerve Growth Factors / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D016627:Oxidopamine