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Journal of Neuroscience, Vol 11, 3070-3078, Copyright © 1991 by Society for Neuroscience
The neurotrophic effects of fibroblast growth factors on dopaminergic neurons in vitro are mediated by mesencephalic glia [published erratum appears in J Neurosci 1992 Mar;12(3):685]
J Engele and MC Bohn
Department of Neurobiology and Anatomy, University of Rochester Medical Center, New York 14642.
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)
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