GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR REVERSES TOXIN-INDUCED INJURY TO MIDBRAIN DOPAMINERGIC-NEURONS IN-VIVO

Fischer 344 rats were unilaterally injected into the medial forebrain bundle with tr-hydroxydopamine (6-OHDA). Apomorphine-induced rotationa l behavior was used to select animals whose rotation exceeded 300 turn s/h, corresponding to greater than 95% dopamine (DA) depletion in the ipsilateral striatum. Four weeks later, glial cell line-derived neurot rophic factor (GDNF) or vehicle was injected intranigrally ipsilateral to the lesion (0.1-100 mu g). The highest dose of GDNF tested produce d a marked decrease in rotational behavior. This dose also produced le vels of DA in the ipsilateral substantia nigra (SN) which were not sta tistically different from the contralateral side. Vehicle-treated anim als showed a marked DA depletion in the ipsilateral SN. These results demonstrate neurochemical and behavioral improvements in unilaterally DA-lesioned rats following intranigral administration of GDNF, suggest ing that GDNF may develop into a useful therapy for Parkinson's diseas e.