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Journal of Neuroscience, Vol 10, 558-570, Copyright © 1990 by Society for Neuroscience
Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors I and II
B Knusel, PP Michel, JS Schwaber and F Hefti
Department of Biological Sciences, University of Southern California, Los Angeles 90089.
To study the selectivity of neurotrophic actions in the brain, we analyzed
the actions of several known growth factors on septal cholinergic, pontine
cholinergic, and mesencephalic dopaminergic neurons in culture. Similar to
nerve growth factor (NGF), basic fibroblast growth factor (bFGF) stimulated
choline acetyltransferase activity in septal cultures. In contrast to NGF,
bFGF also enhanced dopamine uptake in mesencephalic cultures and stimulated
cell proliferation in all 3 culture types. Insulin and the insulin-like
growth factors I and II stimulated transmitter-specific differentiation and
cell proliferation in all culture types. Epidermal growth factor (EGF)
produced a small increase in dopamine uptake by mesencephalic cells and
stimulated cell proliferation in all culture types. In septal cultures,
bFGF was most effective when given at early culture times, NGF at later
times. The stimulatory actions of bFGF and insulin did not require the
presence of glial cells and were not mediated by NGF. In mesencephalic
cultures, the stimulation of dopamine uptake by bFGF and EGF was dependent
on glial proliferation. The results suggest different degrees of
selectivity of the neurotrophic molecules. NGF and, very similarly, bFGF
seem to influence septal cholinergic neurons directly and rather
selectively, whereas the neurotrophic actions of insulin and the
insulin-like growth factors appear to be more general.
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