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ID 51443
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Author
Tayra, Judith Thomas
Kadota, Tomohito
Wang, Feifei
Kikuchi, Yoichiro
Liang, Hanbai
Shinko, Aiko
Wakamori, Takaaki
Vcelar, Brigitta
Weik, Robert
Abstract
Parkinson's disease is characterized by progressive degeneration of dopaminergic neurons. Thus the development of therapeutic neuroprotection and neurorescue strategies to mitigate disease progression is important. In this study we evaluated the neuroprotective/rescue effects of erythropoietin Fc fusion protein (EPO-Fc) and carbamylated erythropoietin Fe fusion protein (CEPO-Fc) in a rat model of Parkinson's disease. Adult female Sprague-Dawley rats received intraperitoneal injection of EPO-Fc, CEPO-Fc or PBS. Behavioral evaluations consisted of rota-rod, cylinder and amphetamine-induced rotation tests. In the neuroprotection experiment, the CEPO-Fc group demonstrated significant improvement compared with the EPO-Fc group on the amphetamine-induced rotation test throughout the four-week follow-up period. Histologically, significantly more tyrosine hydroxylase (TH)-positive neurons were recognized in the substantia nigra (SN) pars compacta in the CEPO-Fc group than in the PBS and EPO-Fc groups. In the neurorescue experiment, rats receiving CEPO-Fc showed significantly better behavioural scores than those receiving PBS. The histological data concerning striatum also showed that the CEPO-Fc group had significantly better preservation of TH-positive fibers compared to the PBS and EPO-Fc groups. Importantly, there were no increases in hematocrit or hemoglobin levels in the CEPO-Fc group in either the neuroprotection or the neurorescue experiments. In conclusion, the newly developed CEPO-Fc might confer neuroprotective and neurorescue benefits in a rat model of Parkinson's disease without the side effects associated with polycythemia. CEPO-Fc might be a therapeutic tool for patients with Parkinson's disease.
Keywords
Carbamylated erythropoietin
Dopamine
Neuroprotection
Neurorescue
Parkinson's disease
Published Date
2013-03-28
Publication Title
Brain Research
Volume
volume1502
Publisher
Elsevier Science Bv
Start Page
55
End Page
70
ISSN
0006-8993
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1016/j.brainres.2013.01.042
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/51453
language
英語
Copyright Holders
(C) 2013 Elsevier B.V. All rights reserved.
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author
Refereed
True
DOI
Web of Sience KeyUT