GDNF improves survival and reduces apoptosis in human embryonic dopaminergic neurons in vitro.
Dopamine cell death is the primary problem limiting the value of neurotransplantation in human patients with Parkinson's disease. To address this problem, we added glial cell line-derived neurotrophic factor (GDNF) to cultures of embryonic dopaminergic neurons obtained from human and from Bonnet monkey (Macaca radiata) in an effort to reduce apoptotic cell death and improve overall cell survival. Tissue from three human embryos, 7-8 weeks post-conception, and one 9-week post-conception monkey embryo were dissociated and cultured in F-12 media with 5% human placental serum. GDNF (10 ng/ml) in human cultures nearly doubled dopamine neuron survival and reduced the rate of apoptosis from 6% to 3%. In monkey cultures, GDNF also enhanced dopamine neuron survival and reduced the apoptotic rate. We conclude that GDNF improves the survival of primate embryonic dopamine neurons in culture by reducing apoptosis.
Clarkson
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ED
Department of Medicine, Division of Clinical Pharmacology, C-237, University of Colorado School of Medicine, 4200 East Ninth Avenue, Denver, CO 80262, USA.
Zawada
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WM
Freed
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CR
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D008255:Macaca radiata; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine