Oligodendrocyte-type-2 astrocyte (O-2A) progenitors increase the survival of rat mesencephalic, dopaminergic neurons from death induced by serum deprivation.
When a primary culture of E16 rat striatal cells was grown in a serum-free medium, treatment with basic fibroblast growth factor (bFGF, 10 ng/ml) caused the generation of the progenitor cell for oligodendrocytes and type-2 astrocytes (O-2A). Immunostaining tests confirmed that > 90% of the cells were positive for A2B5, and < 5% positive for glial fibrillary acidic protein (GFAP). When E14, mesencephalic, dopaminergic neurons were co-cultured with established O-2A progenitor cells in a serum-free growth medium, the survival of tyrosine hydroxylase-positive (TH+) neurons increased 23-fold and 668-fold at the 5th and 10th days, respectively, compared with control cultures plated on poly-D-lysine. Conditioned medium from the O-2A progenitor cultures also decreased the death of TH+ neurons. The mitotic inhibitor, cytosine arabinoside (1.0 microM), did not block the protective effect of the O-2A progenitor cells. O-2A progenitor cells produce a potent, soluble factor, that mediates the increased survival of dopaminergic neurons in vitro.
Takeshima
T
T
Neural Transplantation Unit, LMCN-NINDS-NIH, Bethesda, MD 20892.
Johnston
J M
JM
Commissiong
J W
JW
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003561:Cytarabine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D008636:Mesencephalon / Q000166:cytology*; D017072:Neostriatum / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D051381:Rats; D013234:Stem Cells / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016895:Culture Media, Serum-Free; D005904:Glial Fibrillary Acidic Protein; D003561:Cytarabine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine