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.

• Authors: 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
• Journal: Brain research (Brain Res) Vol. 1502 Pg. 55-70 (Mar 28 2013) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 23380533 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Adrenergic Agents
• Hemoglobins
• Neuroprotective Agents
• Recombinant Proteins
• carbamylated erythropoietin
• Erythropoietin
• Oxidopamine
• Amphetamine
• Tyrosine 3-Monooxygenase

Topics

• Adrenergic Agents (toxicity)
• Amphetamine
• Analysis of Variance
• Animals
• Corpus Striatum (drug effects, metabolism)
• Disease Models, Animal
• Drug Administration Schedule
• Erythropoietin (administration & dosage, analogs & derivatives)
• Female
• Hematocrit
• Hemoglobins (metabolism)
• Neuroprotective Agents (administration & dosage)
• Oxidopamine (toxicity)
• Parkinson Disease (blood, drug therapy, etiology, prevention & control)
• Psychomotor Performance (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (administration & dosage)
• Rotarod Performance Test
• Stereotyped Behavior (drug effects, physiology)
• Substantia Nigra (drug effects, metabolism)
• Time Factors
• Tyrosine 3-Monooxygenase (metabolism)