Asialoerythropoetin is not effective in the R6/2 line of Huntington's disease mice
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/905593
- author
- Gil, Joana LU ; Leist, M ; Popovic, Natalija LU ; Brundin, Patrik LU and Petersén, Åsa LU
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- BMC Neuroscience
- volume
- 5
- publisher
- BioMed Central (BMC)
- 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
- 2016-04-01 15:53:33
- date last changed
- 2022-03-07 02:07:35
@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 (BMC)}},
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}},
doi = {{10.1186/1471-2202-5-17}},
volume = {{5}},
year = {{2004}},
}