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Asialoerythropoetin is not effective in the R6/2 line of Huntington's disease mice

Gil, Joana LU ; Leist, M; Popovic, Natalija LU ; Brundin, Patrik LU and Petersén, Åsa LU (2004) In BMC Neuroscience 5.
Abstract
Background: Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expanded CAG repeat in the HD gene. Both excitotoxicity and oxidative stress have been proposed to play important roles in the pathogenesis of HD. Since no effective treatment is available, this study was designed to explore the therapeutic potential of erythropoietin (EPO), a cytokine that has been found to prevent excitotoxicity, and to promote neurogenesis. To avoid the side effects of a raised hematocrit, we used asialoerythropoietin (asialoEPO), a neuroprotective variant of EPO that lacks erythropoietic effects in mice. R6/2 transgenic HD mice were treated with this cytokine from five to twelve weeks of age. Results: We provide new evidence... (More)
Background: Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expanded CAG repeat in the HD gene. Both excitotoxicity and oxidative stress have been proposed to play important roles in the pathogenesis of HD. Since no effective treatment is available, this study was designed to explore the therapeutic potential of erythropoietin (EPO), a cytokine that has been found to prevent excitotoxicity, and to promote neurogenesis. To avoid the side effects of a raised hematocrit, we used asialoerythropoietin (asialoEPO), a neuroprotective variant of EPO that lacks erythropoietic effects in mice. R6/2 transgenic HD mice were treated with this cytokine from five to twelve weeks of age. Results: We provide new evidence that cell proliferation in the dentate gyrus of the R6/2 hippocampus is reduced by 50% compared to wild-type littermate controls. However, we found that the asialoEPO treatment did not affect the progression of motor symptoms, weight loss or the neuropathological changes. Furthermore, cell proliferation was not enhanced. Conclusions: We conclude that the chosen protocol of asialoEPO treatment is ineffective in the R6/2 model of HD. We suggest that reduced hippocampal cell proliferation may be an important and novel neuropathological feature in R6 HD mice that could be assessed when evaluating potential therapies. (Less)
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publication status
published
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in
BMC Neuroscience
volume
5
publisher
BioMed Central
external identifiers
  • wos:000222247800001
  • scopus:2642545019
ISSN
1471-2202
DOI
10.1186/1471-2202-5-17
language
English
LU publication?
yes
id
8ba3db0d-7f4d-4d93-863e-c7ca154c3563 (old id 905593)
date added to LUP
2008-01-15 13:41:33
date last changed
2017-12-10 04:28:30
@article{8ba3db0d-7f4d-4d93-863e-c7ca154c3563,
  abstract     = {Background: Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expanded CAG repeat in the HD gene. Both excitotoxicity and oxidative stress have been proposed to play important roles in the pathogenesis of HD. Since no effective treatment is available, this study was designed to explore the therapeutic potential of erythropoietin (EPO), a cytokine that has been found to prevent excitotoxicity, and to promote neurogenesis. To avoid the side effects of a raised hematocrit, we used asialoerythropoietin (asialoEPO), a neuroprotective variant of EPO that lacks erythropoietic effects in mice. R6/2 transgenic HD mice were treated with this cytokine from five to twelve weeks of age. Results: We provide new evidence that cell proliferation in the dentate gyrus of the R6/2 hippocampus is reduced by 50% compared to wild-type littermate controls. However, we found that the asialoEPO treatment did not affect the progression of motor symptoms, weight loss or the neuropathological changes. Furthermore, cell proliferation was not enhanced. Conclusions: We conclude that the chosen protocol of asialoEPO treatment is ineffective in the R6/2 model of HD. We suggest that reduced hippocampal cell proliferation may be an important and novel neuropathological feature in R6 HD mice that could be assessed when evaluating potential therapies.},
  author       = {Gil, Joana and Leist, M and Popovic, Natalija and Brundin, Patrik and Petersén, Åsa},
  issn         = {1471-2202},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Neuroscience},
  title        = {Asialoerythropoetin is not effective in the R6/2 line of Huntington's disease mice},
  url          = {http://dx.doi.org/10.1186/1471-2202-5-17},
  volume       = {5},
  year         = {2004},
}