GDNF reduces apoptosis in dopaminergic neurons in vitro.
To explore the mechanism by which glial cell line-derived neurotrophic factor (GDNF) improves cell survival, we measured the apoptotic rate of dopamine neurons incubated with GDNF. Cultures were prepared from embryonic day 15 rat mesencephalon in medium with 5% human placental serum. GDNF reduced the rate of apoptosis in dopamine neurons from 5% to 2%. By contrast, GDNF had no effect on apoptoisis in astrocytes from embryonic mesencephalon or from neonatal cortex. Co-cultures with embryonic striatum as well as with combinations of growth factors were also tested for effects on dopamine neuron survival. Neuronal survival was maximal during co-culture with striatal cells with or without added growth factors. We conclude that GDNF inhibits apoptotic cell death in dopamine neurons.
Clarkson
E D
ED
Department of Medicine, University of Colorado School of Medicine, Denver 80262, USA.
Zawada
W M
WM
Freed
C R
CR
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D004298:Dopamine