Exogenous erythropoietin provides neuroprotection of grafted dopamine neurons in a rodent model of Parkinson's disease
| Autor: | Deanna M. Marchionini, Nicholas M. Kanaan, Timothy J. Collier, Matthew F. Fleming, Caryl E. Sortwell, Susan O. McGuire |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Tyrosine 3-Monooxygenase Cell Survival Cell Transplantation Dopamine Striatum Pharmacology Neuroprotection chemistry.chemical_compound hemic and lymphatic diseases medicine Animals Parkinson Disease Secondary Oxidopamine Erythropoietin Molecular Biology Cells Cultured Neurons biology business.industry General Neuroscience Sympathectomy Chemical Immunohistochemistry Rats Inbred F344 Recombinant Proteins Rats Perfusion Transplantation Neuroprotective Agents Phenotype medicine.anatomical_structure nervous system chemistry Sympatholytics biology.protein Neurology (clinical) Neuron business Neuroscience Developmental Biology Neurotrophin medicine.drug |
| Zdroj: | Brain Research. 1068:221-229 |
| ISSN: | 0006-8993 |
| Popis: | Parkinson's disease (PD) is a neurodegenerative disease marked by severe loss of dopamine (DA) neurons in the nigrostriatal system, which results in depletion of striatal DA. Transplantation of embryonic ventral mesencephalic (VM) DA neurons into the striatum is a currently explored experimental treatment aimed at replacing lost DA in the nigrostriatal system, but is plagued with poor survival (5-20%) of implanted neurons. Here, we tested the ability of erythropoietin (Epo) to provide neuroprotection for embryonic day 14 (E14) VM DA neurons. Epo was tested in vitro for the ability to augment tyrosine hydroxylase-immunoreactive (TH-ir) neuron survival under normal cell culture conditions. In vitro, Epo did not increase the number of TH-ir neurons when administered at the time of plating the E14 VM cells in culture. We also tested the efficacy of Epo to enhance E14 VM transplants in vivo. Rats unilaterally lesioned with 6-hydroxydopamine received transplants that were incubated in Epo. Treatment with Epo produced significant increases in TH-ir neuron number, soma size, and staining intensity. Animals receiving Epo-treated grafts exhibited significantly accelerated functional improvements and significantly greater overall improvements from rotational asymmetry compared to control grafted rats. These data indicate that the survival of embryonic mesencephalic TH-ir neurons is increased when Epo is administered with grafted cells in a rodent model of PD. As direct neurotrophic effects of Epo were not observed in vitro, the mechanism of Epo neuroprotection remains to be elucidated. |
| Databáze: | OpenAIRE |
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