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 factor beta 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.
Sullivan
A M
AM
Department of Neurodegenerative Disorders, Imperial College School of Medicine, Hammersmith Hospital, London, UK. STAN8009@ucc.ie
Pohl
J
J
Blunt
S B
SB
D000818:Animals; D001522:Behavior, Animal; D019485:Bone Morphogenetic Proteins; D016380:Brain Tissue Transplantation; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology / Q000201:enzymology; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006085:Graft Survival / Q000187:drug effects; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D014055:Tomography, Emission-Computed; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D019485:Bone Morphogenetic Proteins; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016212:Transforming Growth Factor beta; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine