The neurotrophic effects of fibroblast growth factors on dopaminergic neurons in vitro are mediated by mesencephalic glia.
Neurotrophic support is generally believed to result from a direct action of growth factors on developing neurons. However, there is increasing evidence that growth factors can indirectly affect neuronal development by glial-mediated processes. To investigate a possible role of glia in mediating neurotrophic effects on dopaminergic neurons, four purified growth factors were screened for dual effects on the survival and differentiation of dopaminergic neurons and on the proliferation of mesencephalic glial cells in vitro. Dissociated embryonic day 14.5 rat mesencephalon was grown at low cell density without serum, conditions under which both glial growth and neuronal survival are not optimal. Treatment of these cultures with acidic fibroblast growth factor (aFGF) or basic fibroblast growth factor (bFGF) increased the number of surviving tyrosine hydroxylase-immunoreactive (TH-IR) neurons by 90-110% [corrected] at 8 d in vitro in a dose-dependent manner. The effects of these factors were not additive. High-affinity dopamine uptake was increased by bFGF, but not by aFGF. Length of TH-IR neurites was not affected by either aFGF or bFGF. Both growth factors induced proliferation of mesencephalic astrocytes as demonstrated by autoradiographic labeling with 3H-thymidine combined with immunocytochemistry for glial fibrillary acidic protein (GFAP). In contrast, platelet-derived growth factor (PDGF) and interleukin-1 had no effect on the survival or differentiation of dopaminergic neurons or the proliferation of mesencephalic astrocytes. Inhibition of glial proliferation abolished the neurotrophic effects exerted by aFGF or bFGF on dopaminergic neurons. Moreover, conditioned medium derived from mesencephalic glial cultures replated in the virtual absence of neurons also contained neurotrophic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neurobiology and Anatomy, University of Rochester Medical Center, New York 14642.
J
J
Engele
M C
MC
Bohn
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004298:Dopamine / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology / Q000502:physiology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009433:Neural Inhibition; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology
D003470:Culture Media; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D005346:Fibroblast Growth Factors; D004298:Dopamine