Abstract
Growth/differentiation factor 5 (GDF5) is a neurotrophic factor that promotes the survival of midbrain dopaminergic neurons in vitro and in vivo and as such is potentially useful in the treatment of Parkinson's disease (PD). This study shows that a continuous supply of GDF5, produced by transplanted GDF5-overexpressing CHO cells in vivo, has neuroprotective and neurorestorative effects on midbrain dopaminergic neurons following 6-hydroxydopamine (6-OHDA)-induced lesions of the adult rat nigrostriatal pathway. It also increases the survival and improves the function of transplanted embryonic dopaminergic neurons in the 6-OHDA-lesioned rat model of PD. This study provides the first proof-of-principle that sustained delivery of GDF5 in vivo may be useful in the treatment of PD.
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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CHO Cells
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Cell Culture Techniques
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Cell Differentiation
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Cell Survival
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Cricetinae
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Disease Models, Animal
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Dopaminergic Neurons / cytology
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Dopaminergic Neurons / transplantation
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Female
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Gene Expression Regulation
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Gene Transfer Techniques
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Growth Differentiation Factor 5 / genetics*
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Growth Differentiation Factor 5 / metabolism
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Humans
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Immunohistochemistry
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Immunosuppression Therapy
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Mesencephalon / cytology
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Mesencephalon / embryology
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Mesencephalon / transplantation*
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Multivariate Analysis
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Nerve Growth Factors / genetics
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Nerve Growth Factors / metabolism
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Neuroprotective Agents / metabolism*
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Oxidopamine / metabolism
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Parkinson Disease / genetics
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Parkinson Disease / pathology*
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Parkinson Disease / therapy*
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Rats
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Rats, Sprague-Dawley
Substances
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GDF5 protein, human
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Growth Differentiation Factor 5
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Nerve Growth Factors
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Neuroprotective Agents
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Oxidopamine