Growth factors improve immediate survival of embryonic dopamine neurons after transplantation into rats.
Embryonic dopamine neurons survive poorly after transplant into models of Parkinson's disease, possibly due to programmed cell death (apoptosis). Apoptosis in cultured dopamine neurons can be reduced by growth factors such as glial cell line-derived neurotrophic factor (GDNF) or a combination of insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF). To improve the survival of dopamine neurons in grafts, strands of E15 rat ventral mesencephalon were pretreated with a combination of GDNF, IGF-I, and bFGF and then transplanted into 6-hydroxydopamine-lesioned rats. In control animals, only 32% of dopamine neuron profiles survived the first 24 h after transplant. Growth factor pretreatment increased survival to 49% on day 1. Growth factors reduced the apoptotic rate of transplanted cells, just as they had in the previous in vitro experiments. Apoptotic nuclear morphology was observed in the transplanted dopamine neurons. We conclude that the majority of transplanted dopamine neurons die in grafts within the first 24 h after transplant, most likely by an apoptotic mechanism. Prevention of apoptosis with anti-apoptotic agents may improve the viability of dopamine neurons grafted for Parkinson's disease.
Zawada
W M
WM
Department of Medicine, University of Colorado School of Medicine, 4200 East Ninth Avenue, Denver, CO 80262, USA. mike.zawada@uchsc.edu
Zastrow
D J
DJ
Clarkson
E D
ED
Adams
F S
FS
Bell
K P
KP
Freed
C R
CR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D016332:Fetal Tissue Transplantation; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006133:Growth Substances / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000637:transplantation; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D051381:Rats / Q000196:embryology; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006133:Growth Substances; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D007334:Insulin-Like Growth Factor I; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine