Growth/differentiation factor 5 and glial cell line-derived neurotrophic factor enhance survival and function of dopaminergic grafts in a rat model of Parkinson's disease

Growth/differentiation factor 5 is a member of the transforming growth fact or beta superfamily, which has neurotrophic and neuroprotective effects on dopaminergic neurons both in vitro and in vivo. Here we investigate the eff ects of growth/differentiation factor 5 on foetal mesencephalic grafts tran splanted into a rat model of Parkinson's disease, and compare them with tho se of glial cell line-derived neurotrophic factor. Mesencephalic tissue was suspended in solutions containing either growth/differentiation factor 5 o r glial cell line-derived neurotrophic factor prior to transplantation into the left striatum of rats with 6-hydroxydopamine lesions of the left media l forebrain bundle. Both proteins enhanced graft-induced compensation of am phetamine-stimulated rotations. Positron emission tomography studies showed that both neurotrophins increased graft-induced recovery of striatal bindi ng of [C-11]RTI-121, a marker for dopaminergic nerve terminals. Post mortem analysis at 8 weeks after transplantation showed that both neurotrophins s ignificantly increased the survival of grafted dopaminergic neurons. This s tudy shows that growth/differentiation factor 5 is at least as effective as glial cell line-derived neurotrophic factor in enhancing the survival and functional activity of mesencephalic grafts, and thus is an important candi date for use in the treatment of Parkinson's disease.