Present address: Department of Anatomy, University College Cork, Cork, Ireland.
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
Version of Record online: 25 DEC 2001
European Journal of Neuroscience
Volume 10, Issue 12, pages 3681–3688, December 1998
How to Cite
Sullivan, A. M., Pohl, J. and Blunt, S. B. (1998), 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. European Journal of Neuroscience, 10: 3681–3688. doi: 10.1046/j.1460-9568.1998.00378.x
- Issue online: 25 DEC 2001
- Version of Record online: 25 DEC 2001
- Received 15 April 1998, revised 3 July 1998, accepted 10 July 1998
- neural transplantation;
- positron emission tomography
Growth/differentiation factor 5 is a member of the transforming growth factor β 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.