GLIAL-CELL LINE-DERIVED NEUROTROPHIC GROWTH-FACTOR INHIBITS APOPTOTICDEATH OF POSTNATAL SUBSTANTIA-NIGRA DOPAMINE NEURONS IN PRIMARY CULTURE

Glial cell line-derived neurotrophic factor (GDNF) was identified on t he basis of its ability to enhance the development of embryonic mesenc ephalic dopamine neurons. It remains unknown whether GDNF is a physiol ogically relevant trophic factor for these neurons. We have shown that natural cell death among dopamine neurons of the substantia nigra occ urs largely postnatally. To investigate whether GDNF may have the abil ity to support these neurons during their period of natural cell death , we have used a postnatal primary culture model. We find that GDNF is able to support the viability of postnatal nigral dopamine neurons by inhibiting apoptotic death. This ability of GDNF shows both regional specificity for the nigra and cellular specificity for the dopamine ph enotype. Among eight other neurotrophic factors previously reported to support embryonic dopamine neurons, GDNF was unique in this ability. Thus, GDNF meets this criterion for a physiologically relevant trophic factor for dopamine neurons of the substantia nigra.