Adult Neural Stem/Progenitor Cells in the Forebrain - Drugs of Abuse: Neurological Reviews and Protocols - page 33

birth according to their characteristic morphology of granule neurons and
co-expression with the neuronal markers, such as neuron specifi c enolase
(NSE), microtubule-associated protein-2 (MAP-2), or neuronal nuclear antigen
(NeuN). A small fraction of newborn cells (~15%) adopt a glial fate as detected
by their association with the astrocytic (glial fi brillary acidic protein [(GFAP])
or S100 ) or oligodendrocytic markers. Newborn neurons in the adult dentate

gyrus can migrate to the functional site, where they execute the programmed
missions and connect appropriately into the circuitry of the hippocampus by
developing synapses and axonal projections to receive and deliver signals,
respectively (12) .
Besides the SVZ and the dentate gyrus, active adult neurogenesis and/or
gliogenesis exist in other brain regions. The drug-affected area, striatum, is
among those regions where cell proliferation and differentiation recently have
been noticed (13) . After BrdU injection, cell division is consistently observed
in the dorsal and ventral striatum. Divided cells are scattered throughout the
area. Newborn striatal cells survive beyond 60 d, with a graduate increase
in their body size and processes (13 , 14) . Although a small fraction of cells
exhibit the morphological characteristics of radial glia 3 wk after birth, the vast
majority of newborn cells show no obvious morphology of either projection
neurons or glia. Parallel with the morphological observations, approx 10-20%
of BrdU-labeled cells are immunoreactive to S100

and no BrdU cells are
double labeled with NeuN even 6 wk after birth. Thus, it appears that gliogen-
esis, but not neurogenesis, naturally occurs in the intact striatum at a small scale,
and the vast majority of newborn cells normally remain undifferentiated in this
brain area. The exact primitive stage of those dividing cells in the striatum is not
yet defi ned. However, the aforementioned study clearly demonstrates that these
cells could self-renew and give rise to at least glia in the adult striatum.

3. Regulation of Adult Neurogenesis and Gliogenesis
A great deal of effort recently has been made in animal experiments to
explore the regulation of adult neurogenesis/gliogenesis in the CNS by a
variety of experimental manipulations. Available data show that growth factors
have signifi cant effects on the behavior of neural progenitor's both in vivo and
in vitro. For example, basic fi broblast growth factor (bFGF) and epidermal
growth factor (EGF) infused into the lateral ventricle of adult rats and mice
profoundly increase proliferation of cells in the SVZ, but not in the dentate
gyrus of the hippocampus (15-18) . Moreover, the two growth factors tend
to infl uence the fate of cells, usually resulting in more glial cells and fewer
neurons (15-18) . Increased systemic levels of bFGF by subcutaneous injection
also increase cell proliferation in both the SVZ and hippocampus of neonatal