Oligodendrocyte-type 2 astrocyte-derived trophic factors increase survival of developing dopamine neurons through the inhibition of apoptotic cell death.
Survival of embryonic dopamine (DA) neurons is extremely low (5-20%) following transplantation. Strategies to increase this survival are critical to the future of transplantation for Parkinson's disease. We demonstrate here that a factor(s) released from striatal oligodendrocyte-type 2 astrocytes (SO2A) greatly improves the survival and phenotype expression of mesencephalic DA neurons in culture while simultaneously decreasing the presence of apoptotic nuclear profiles, as detected by the TUNEL method and bisbenzamide/tyrosine hydroxylase double labeling. This SO2A-derived trophic factor(s) has minimal effects on glia and no effect on nondopaminergic mesencephalic neurons. The developmental period during which this SO2A trophic effect occurs (E14-18) coincides with the period when mesencephalic grafts are undergoing the highest rates of apoptosis, i.e., immediately following implantation. Therefore, SO2A-derived trophic factor(s) offers great potential for the augmentation of grafted DA neuron survival.
Sortwell
C E
CE
Department of Neurological Sciences and Research Center for Brain Repair, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA. csortwel@rush.edu
Daley
B F
BF
Pitzer
M R
MR
McGuire
S O
SO
Sladek
J R
JR
Collier
T J
TJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D016380:Brain Tissue Transplantation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D009336:Necrosis; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010300:Parkinson Disease / Q000628:therapy; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors; D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine