MESENCEPHALIC DOPAMINERGIC-NEURONS PROTECTED BY GDNF FROM AXOTOMY-INDUCED DEGENERATION IN THE ADULT BRAIN

GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF) promotes survival o f embryonic dopaminergic neurons in culture(1), and its expression pat tern suggests a role as a transient target-derived trophic factor for dopaminergic neurons of the substantia nigra(2-4). These neurons parti cipate in the control of motor activity, emotional status and cognitio n(5), and they degenerate in Parkinson's disease for unknown reasons. To test whether GDNF has a trophic effect on dopaminergic neurons in t he adult brain, we used a rat model in which these neurons are induced to degenerate by transecting their axons within the medial forebrain bundle(6). We report here that axotomy resulted in loss of half the ty rosine hydroxylase-expressing neurons in the substantia nigra. This lo ss was largely prevented by repeated injections of GDNF adjacent to th e substantia nigra. Our findings suggest that GDNF or related molecule s may be useful for the treatment of Parkinson's disease.