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Volume 17, Number 15,
Issue of August 1, 1997
pp. 5820-5829
Copyright ©1997 Society for Neuroscience
Epidermal Growth Factor and Fibroblast Growth Factor-2 Have
Different Effects on Neural Progenitors in the Adult Rat Brain
Received Dec. 11, 1996; revised March 27, 1997; accepted May 9, 1997.
H. Georg Kuhn1,
Jürgen Winkler2, 3,
Gerd Kempermann1,
Leon J. Thal2, 3, and
Fred H. Gage1
1 Laboratory of Genetics, The Salk Institute, La Jolla,
California 92186, 2 Department of Neurosciences, University
of California San Diego, La Jolla, California 92093, and
3 Neurology Service (127), Veterans Affairs Medical Center,
La Jolla, California 92161
Neurons and glia are generated throughout adulthood from
proliferating cells in two regions of the rat brain, the subventricular zone (SVZ) and the hippocampus. This study shows that exogenous basic
fibroblast growth factor (FGF-2) and epidermal growth factor (EGF) have
differential and site-specific effects on progenitor cells in
vivo. Both growth factors expanded the SVZ progenitor population after 2 weeks of intracerebroventricular administration, but
only FGF-2 induced an increase in the number of newborn cells, most
prominently neurons, in the olfactory bulb, the normal destination for
neuronal progenitors migrating from the SVZ. EGF, on the other hand,
reduced the total number of newborn neurons reaching the olfactory bulb
and substantially enhanced the generation of astrocytes in the
olfactory bulb. Moreover, EGF increased the number of newborn cells in
the striatum either by migration of SVZ cells or by stimulation of
local progenitor cells. No evidence of neuronal differentiation of
newborn striatal cells was found by three-dimensional confocal analysis, although many of these newborn cells were associated closely
with striatal neurons. The proliferation of hippocampal progenitors was
not affected by either growth factor. However, EGF increased the number
of newborn glia and reduced the number of newborn neurons, similar to
the effects seen in the olfactory bulb. These findings may be useful
for elucidating the in vivo role of growth factors in
neurogenesis in the adult CNS and may aid development of neuronal
replacement strategies after brain damage.
Key words:
subventricular zone;
hippocampus;
epidermal growth
factor;
basic fibroblast growth factor;
intracerebroventricular
administration;
progenitor cells;
stem cells;
proliferation;
neurogenesis;
gliogenesis
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