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.