Abstract
Glial cell line-derived neurotrophic factor (GDNF) is a potent and specific neurotrophic factor for dopaminergic neurons. GDNF has been previously shown to protect dopaminergic neurons from lesion-induced degeneration in vivo. In this study we investigated the effect of GDNF on 6-hydroxydopamine (6-OHDA)-treated dopaminergic neurons in vitro. In dissociated cultures of embryonic rat mesencephalon, 6-OHDA exhibited a dose-dependent cytotoxicity on tyrosine hydroxylase (TH)-immunoreactive neurons. After pre-treatment with GDNF, however, 6-OHDA-induced loss of dopaminergic neurons was effectively reduced. It has been shown recently that GDNF signals through the receptor tyrosine kinase Ret and the GDNF receptor-alpha (GFR-alpha). By RT-PCR, we found both Ret- and GFR-alpha-genes to be expressed in the cultured mesencephalic cells. We propose that the neuroprotective effect of GDNF on 6-OHDA-treated dopaminergic neurons in vitro is most likely mediated by functional Ret receptor signaling pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Survival / drug effects*
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Cells, Cultured
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Dopamine / physiology*
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Drosophila Proteins*
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Embryo, Mammalian
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Gene Expression Regulation / drug effects
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Glial Cell Line-Derived Neurotrophic Factor
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Glial Cell Line-Derived Neurotrophic Factor Receptors
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Mesencephalon / cytology*
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Nerve Growth Factors*
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Nerve Tissue Proteins / pharmacology*
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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Neuroprotective Agents / pharmacology*
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Oxidopamine / antagonists & inhibitors
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Oxidopamine / toxicity*
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-ret
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Rats
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Receptor Protein-Tyrosine Kinases / genetics*
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Receptor Protein-Tyrosine Kinases / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Tyrosine 3-Monooxygenase / metabolism
Substances
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Drosophila Proteins
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Gdnf protein, rat
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Glial Cell Line-Derived Neurotrophic Factor
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Glial Cell Line-Derived Neurotrophic Factor Receptors
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Nerve Growth Factors
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Nerve Tissue Proteins
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Neuroprotective Agents
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Proto-Oncogene Proteins
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Oxidopamine
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Tyrosine 3-Monooxygenase
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases
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Ret protein, Drosophila
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Ret protein, rat
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Dopamine