Adenovirus-mediated over-expression of TGFbeta1 in the striatum decreases dopaminergic cell survival in embryonic nigral grafts.
Neurotrophic factors may be valuable for improving the survival and the functional efficacy of fetal nigral grafts to treat Parkinson's disease (PD). However, further characterization of their effects is required. New methods of protein delivery also need to be explored to supply sustained and regulated levels of these molecules. Gene transfer via adenoviral vectors is a promising strategy for this purpose. We show herein the effect of adenovirus-mediated transforming growth factor beta1 (TGFbeta1) gene transfer on fetal nigral grafts in a rat model of PD. Direct injection of AdTGFbeta1 into the dopamine-depleted striatum decreased the survival of the transplanted tyrosine hydroxylase-positive (TH+) neurons and impaired the functional efficacy of grafts. Viral toxicity to the graft was avoided by separating the site of viral infection from the transplant by a distance that allowed TGFbeta1 effect on the graft. This infection protocol may be useful for delivering secreted molecules with neurotrophic effects to dopaminergic grafts.
Sánchez-Capelo
A
A
Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR C9923, Hôpital de la Pitié Salpêtrière, Paris, France.
Corti
O
O
Mallet
J
J
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002470:Cell Survival / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology; D005260:Female; D016332:Fetal Tissue Transplantation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000196:embryology / Q000637:transplantation; D016212:Transforming Growth Factor beta / Q000235:genetics*
D016212:Transforming Growth Factor beta; D004298:Dopamine