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Comparative analysis of the effects of neurotrophic factors CDNF and GDNF in a nonhuman primate model of Parkinson’s disease

Garea-Rodríguez, Enrique; Eesmaa, Ave; Lindholm, Päivi K; Schlumbohm, Christina; König, Jessica; Meller, Birgit; Krieglstein, Kerstin; Helms, Gunther LU ; Saarma, Mart and Fuchs, Eberhard (2016) In PLoS ONE 11(2). p.1-21
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... (More)
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. (Less)
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author
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Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
11
issue
2
pages
1 - 21
publisher
Public Library of Science
external identifiers
  • scopus:84960977115
ISSN
1932-6203
DOI
10.1371/journal.pone.0149776
language
English
LU publication?
yes
id
3f6edcf1-3ea2-4e17-8f34-538c5b2e2cac (old id 8772474)
date added to LUP
2016-02-27 01:15:43
date last changed
2017-11-05 04:12:12
@article{3f6edcf1-3ea2-4e17-8f34-538c5b2e2cac,
  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<br/><br>
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<br/><br>
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.},
  author       = {Garea-Rodríguez, Enrique and Eesmaa, Ave and Lindholm, Päivi K and Schlumbohm, Christina and König, Jessica and Meller, Birgit and Krieglstein, Kerstin and Helms, Gunther and Saarma, Mart and Fuchs, Eberhard},
  issn         = {1932-6203},
  language     = {eng},
  number       = {2},
  pages        = {1--21},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Comparative analysis of the effects of neurotrophic factors CDNF and GDNF in a nonhuman primate model of Parkinson’s disease},
  url          = {http://dx.doi.org/10.1371/journal.pone.0149776},
  volume       = {11},
  year         = {2016},
}