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

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Garea-Rodriguez , E , Eesmaa , A , Lindholm , P K , Schlumbohm , C , König , J , Meller , B , Krieglstein , K , Helms , G , Saarma , M & Fuchs , E 2016 , ' Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson's Disease ' , PLoS One , vol. 11 , no. 2 , 0149776 . https://doi.org/10.1371/journal.pone.0149776

Title: Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson's Disease
Author: Garea-Rodriguez, Enrique; Eesmaa, Ave; Lindholm, Päivi Katariina; Schlumbohm, Christina; König, Jessica; Meller, Birgit; Krieglstein, Kerstin; Helms, Gunther; Saarma, Mart; Fuchs, Eberhard
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
Date: 2016-02-22
Language: eng
Number of pages: 21
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/166063
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 unlesionedmonkeys and analyzed the amino acid sequence ofmarmoset CDNF. The severity of 6-OHDA lesions and treatment effects weremonitored 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.
Subject: CONVECTION-ENHANCED DELIVERY
COMMON MARMOSET MONKEY
MIDBRAIN DOPAMINE NEURONS
HUMAN ALPHA-SYNUCLEIN
IN-VIVO
RAT MODEL
FUNCTIONAL RECOVERY
SUBSTANTIA-NIGRA
RHESUS-MONKEYS
KDEL RECEPTORS
1182 Biochemistry, cell and molecular biology
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