Abstract
The protective effects of adenovirus-mediated glia cell line-derived neurotrophic factor (GDNF) gene transaction was investigated on cultured motoneurons. First, the dose- and time-response relationship of glutamate neurotoxicity was determined on spinal motoneuron cultures. Then, the effect of the gdnf recombinant adenovirus (AdCMVgdnf) was tested in this cellular model. AdCMVgdnf at 20 MOI (multiplicity of infection) was found to significantly reduce the cell loss of motoneurons, as compared to AdCMVgdnf at 20 MOI, the recombinant adenovirus containing the marker gene lacZ. Furthermore, the adenovirus was proved to mediate erogenous gene expression using X-Gal staining and a semi-quantitative RT-PCR method. These results suggested a therapeutic potential of adenovirus vector-mediated gdnf gene therapy in human motoneuron diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Animals
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Cell Survival / genetics
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Cells, Cultured / drug effects*
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Cells, Cultured / metabolism
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Cells, Cultured / pathology
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Dose-Response Relationship, Drug
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Fetus
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Gene Expression Regulation, Viral / physiology
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Genes, Reporter / physiology
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Genetic Vectors / therapeutic use*
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Glial Cell Line-Derived Neurotrophic Factor
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Glutamic Acid / metabolism
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Glutamic Acid / pharmacology*
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Motor Neuron Disease / drug therapy
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Motor Neuron Disease / metabolism
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Motor Neuron Disease / physiopathology
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Motor Neurons / drug effects*
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Motor Neurons / metabolism
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Motor Neurons / pathology
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Nerve Growth Factors*
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Nerve Tissue Proteins / genetics*
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Neuroprotective Agents / metabolism*
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Neurotoxins / antagonists & inhibitors*
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RNA, Messenger / metabolism
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Rats
Substances
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Gdnf protein, rat
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Glial Cell Line-Derived Neurotrophic Factor
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Nerve Growth Factors
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Nerve Tissue Proteins
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Neuroprotective Agents
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Neurotoxins
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RNA, Messenger
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Glutamic Acid