The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson's disease

Judith Thomas Tayra, Masahiro Kameda, Takao Yasuhara, Takashi Agari, Tomohito Kadota, Feifei Wang, Yoichiro Kikuchi, Hanbai Liang, Aiko Shinko, Takaaki Wakamori, Brigitta Vcelar, Robert Weik, Isao Date

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 Fc 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.

Original languageEnglish
Pages (from-to)55-70
Number of pages16
JournalBrain Research
Volume1502
DOIs
Publication statusPublished - 2013

Fingerprint

Neuroprotective Agents
Parkinson Disease
Proteins
Tyrosine 3-Monooxygenase
Amphetamine
carbamylated erythropoietin
Polycythemia
Dopaminergic Neurons
Erythropoietin
Intraperitoneal Injections
Hematocrit
Sprague Dawley Rats
Disease Progression
Hemoglobins
Neurons

Keywords

  • Carbamylated erythropoietin
  • Dopamine
  • Neuroprotection
  • Neurorescue
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson's disease. / Thomas Tayra, Judith; Kameda, Masahiro; Yasuhara, Takao; Agari, Takashi; Kadota, Tomohito; Wang, Feifei; Kikuchi, Yoichiro; Liang, Hanbai; Shinko, Aiko; Wakamori, Takaaki; Vcelar, Brigitta; Weik, Robert; Date, Isao.

In: Brain Research, Vol. 1502, 2013, p. 55-70.

Research output: Contribution to journalArticle

Thomas Tayra, Judith ; Kameda, Masahiro ; Yasuhara, Takao ; Agari, Takashi ; Kadota, Tomohito ; Wang, Feifei ; Kikuchi, Yoichiro ; Liang, Hanbai ; Shinko, Aiko ; Wakamori, Takaaki ; Vcelar, Brigitta ; Weik, Robert ; Date, Isao. / The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson's disease. In: Brain Research. 2013 ; Vol. 1502. pp. 55-70.
@article{6147031c1c0b44659d3822dbd222d581,
title = "The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson's disease",
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 Fc 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",
author = "{Thomas Tayra}, Judith and Masahiro Kameda and Takao Yasuhara and Takashi Agari and Tomohito Kadota and Feifei Wang and Yoichiro Kikuchi and Hanbai Liang and Aiko Shinko and Takaaki Wakamori and Brigitta Vcelar and Robert Weik and Isao Date",
year = "2013",
doi = "10.1016/j.brainres.2013.01.042",
language = "English",
volume = "1502",
pages = "55--70",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

TY - JOUR

T1 - The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson's disease

AU - Thomas Tayra, Judith

AU - Kameda, Masahiro

AU - Yasuhara, Takao

AU - Agari, Takashi

AU - Kadota, Tomohito

AU - Wang, Feifei

AU - Kikuchi, Yoichiro

AU - Liang, Hanbai

AU - Shinko, Aiko

AU - Wakamori, Takaaki

AU - Vcelar, Brigitta

AU - Weik, Robert

AU - Date, Isao

PY - 2013

Y1 - 2013

N2 - 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 Fc 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.

AB - 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 Fc 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.

KW - Carbamylated erythropoietin

KW - Dopamine

KW - Neuroprotection

KW - Neurorescue

KW - Parkinson's disease

UR - http://www.scopus.com/inward/record.url?scp=84875453515&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875453515&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2013.01.042

DO - 10.1016/j.brainres.2013.01.042

M3 - Article

C2 - 23380533

AN - SCOPUS:84875453515

VL - 1502

SP - 55

EP - 70

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -