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Volume 16, Number 22, Issue of November 15, 1996 pp. 7206-7215
Copyright ©1996 Society for Neuroscience

Short-Term GDNF Treatment Provides Long-Term Rescue of Lesioned Nigral Dopaminergic Neurons in a Rat Model of Parkinson's Disease

Received May 22, 1996; revised Aug. 19, 1996; accepted Aug. 22, 1996.

Christian Winkler^{1, 2}, Hansjörg Sauer^{1, 3}, Chong S. Lee^{1, 4}, and Anders Björklund¹

¹ Lund University, Wallenberg Neuroscience Center, S-22362 Lund, Sweden, ² Neurosurgical Clinic, Nordstadt Hospital, D-30167 Hannover, Germany, ³ Genentech Inc., South San Francisco, California 94080, ⁴ Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, British Columbia, Canada V6T 2B5

Glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neuroprotective effects on dopamine (DA) neurons in vivo. Here we report long-term rescue of nigral DA neurons after delayed short-term GDNF administration in a rat lesion model that reproduces the slowly progressing degenerative process seen in Parkinson's disease. GDNF injected close to the substantia nigra provided near-complete protection and persistent survival of the lesioned nigral neurons for at least 4 months after discontinuation of GDNF treatment. Long-term rescue of the nigral cells, however, was not accompanied by any significant reinnervation of the lesioned striatal target or any signs of functional recovery in either drug-induced or spontaneous motor behaviors. We conclude that not only preservation of the nigral DA neurons but also restoration of striatal DA function is necessary for functional recovery in the rat Parkinson model.

Key words: GDNF; substantia nigra; striatum; neurodegeneration; behavior; Parkinson's disease

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