Growth factors rescue embryonic dopamine neurons from programmed cell death.
Poor survival of embryonic dopamine neurons is a primary problem limiting the value of neurotransplantation for Parkinson's disease. Several neurotrophic factors have been shown to promote dopamine neuron survival when used individually in culture. We have found that two peptides, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF), have additive effects on cell survival when used in combination. These growth factors reduced the number of dopamine cells undergoing apoptotic cell death. The neurotrophic factors induced proliferation of astrocytes but not dopamine neurons. When cell proliferation was blocked by cytosine arabinoside, the beneficial effects of IGF-I and bFGF were abolished, suggesting that effects of the growth factors were mediated, at least in part, by factors associated with glia. These results indicate that growth factors in combination may prove useful for enhancing dopamine neuron survival for neurotransplantation.
Zawada
W M
WM
Division of Clinical Pharmacology-C237, University of Colorado School of Medicine, Denver, Colorado 80262, USA.
Kirschman
D L
DL
Cohen
J J
JJ
Heidenreich
K A
KA
Freed
C R
CR
D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*
D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D004298:Dopamine