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  • Title: Glial cell line-derived neurotrophic factor protects dopaminergic neurons from 6-hydroxydopamine toxicity in vitro.
    Author: Eggert K, Schlegel J, Oertel W, Würz C, Krieg JC, Vedder H.
    Journal: Neurosci Lett; 1999 Jul 16; 269(3):178-82. PubMed ID: 10454161.
    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.
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