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.
authors: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors: Judith
authors: J
authors: Thomas Tayra
authors: Masahiro
authors: M
authors: Kameda
authors: Takao
authors: T
authors: Yasuhara
authors: Takashi
authors: T
authors: Agari
authors: Tomohito
authors: T
authors: Kadota
authors: Feifei
authors: F
authors: Wang
authors: Yoichiro
authors: Y
authors: Kikuchi
authors: Hanbai
authors: H
authors: Liang
authors: Aiko
authors: A
authors: Shinko
authors: Takaaki
authors: T
authors: Wakamori
authors: Brigitta
authors: B
authors: Vcelar
authors: Robert
authors: R
authors: Weik
authors: Isao
authors: I
authors: Date
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000661:Amphetamine; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D045442:Rotarod Performance Test; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D006454:Hemoglobins; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; C488171:carbamylated erythropoietin; D004921:Erythropoietin; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase