Glial cell line-derived neurotrophic factor protects dopaminergic neurons from 6-hydroxydopamine toxicity in vitro.
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.
Eggert
K
K
Department of Neurology, Philipps-University of Marburg, Germany. eggert@mailer.uni-marburg.de
Schlegel
J
J
Oertel
W
W
Würz
C
C
Krieg
J C
JC
Vedder
H
H
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004298:Dopamine / Q000502:physiology*; D029721:Drosophila Proteins; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008636:Mesencephalon / Q000166:cytology*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D029721:Drosophila Proteins; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C495001:Ret protein, rat; D004298:Dopamine