Peer-Reviewed Journal Details
Mandatory Fields
Sullivan A.;Pohl J.;Blunt S.
The European Journal of Neuroscience
Growth/differentiation factor 5 and glial cell line-derived neurotrpphic factor enhance survival and function of dopaminergic grafts in a rat model of Parkinson's disease
Scopus: 69 ()
Optional Fields
6-hydroxydopamine Neural transplantation Neuroprotection Position emission tomography
Growth/differentiation factor 5 is a member of the transforming growth factor superfamily, which has neurotrophic and neuroprotective effects on dopaminergic neurons both in vitro and in vivo. Here we investigate the effects of growth/differentiation factor 5 on foetal mesencephalic grafts transplanted into a rat model of Parkinson's disease, and compare them with those of glial cell line-derived neurotrophic factor. Mesencephalic tissue was suspended in solutions containing either growth/differentiation factor 5 or glial cell line-derived neurotrophic factor prior to transplantation into the left striatum of rats with 6-hydroxydopamine lesions of the left medial forebrain bundle. Both proteins enhanced graft-induced compensation of amphetamine-stimulated rotations. Positron emission tomography studies showed that both neurotrophins increased graft-induced recovery of striatal binding of [11C]RTI-121, a marker for dopaminergic nerve terminals. Post mortem analysis at 8 weeks after transplantation showed that both neurotrophins significantly increased the survival of grafted dopaminergic neurons. This study 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 candidate for use in the treatment of Parkinson's disease. European Neuroscience Association.
Grant Details