Neuroprotective effects of delayed administration of growth/differentiation factor-5 in the partial lesion model of Parkinson's disease

Neurotrophic factors have the potential for therapeutic use in Parkinson's disease (PD) to support the remaining dopaminergic neurons and protect them against the ongoing disease process. We have examined the effects of the neurotrophin growth and differentiation factor-5 (GDF-5) in a rat model of Parkinson's disease, the intrastriatal 6-hydroxydopamine (6-OHDA) lesion. GDF-5 (25 mug) was injected into either the striatum or substantia nigra (SN) of adult rats at I or 2 weeks after 6-hydroxydopamine administration. The behavioral effects of GDF-5 treatment were examined in vivo by amphetamine-induced rotational testing. Injection of GDF-5 into the nigra at either I or 2 weeks, or into the striatum at 1 week, after the lesion induced significant decreases in rotations. Post-mortem immunocytochemistry after 6 weeks showed that GDF-5 administration into either site protected dopaminergic cell bodies of the nigra when injected at I but not 2 weeks after 6-hydroxydopamine. However, no significant protection of striatal dopaminergic fiber density was observed after GDF-5 treatment. This study shows that the delayed administration of a single dose of GDF-5 has significant protective effects on the damaged adult rat nigrostriatal pathway, reinforcing its therapeutic potential for Parkinson's disease. (C) 2003 Elsevier Inc. All rights reserved.