Adult Neural Stem/Progenitor Cells in the Forebrain - Drugs of Abuse: Neurological Reviews and Protocols - page 32

cells usually show low levels of cell division under normal conditions and
have already made a commitment to become neural tissues. Natural prolifera-
tion and differentiation of neural progenitor cells generate either neuronal
cells (neurogenesis) or glial cells (gliogenesis). Increasing evidence shows
that proliferation and/or differentiation of progenitors can be altered substan-
tially by exogenous administration of growth factors or other experimental
manipulations.
Exposure to psychostimulants such as cocaine and amphetamine causes
long-term mental illnesses. Brain mechanisms underlying biological actions of
these stimulants are not well understood and may be related to changes in the
mesolimbic and mesostriatal dopaminergic pathways. It has been suggested
that drug exposure causes various cellular and molecular changes in the
dopaminergic system, which lead to the development of psychoplasticity related
to long-term properties of drugs of abuse. However, identifi cation of altered
neural elements responsible for psychoplasticity has not been achieved despite
multidisciplinary efforts during the past few decades. Given the existence
of active neural progenitor cells in several key structures of the forebrain,
alteration in proliferation and/or differentiation of progenitors under dopamine-
stimulated conditions might participate in the formation of psychoplasticity.
This is indeed supported by the observations from recently emerging animal
studies summarized in this chapter.
2. Adult Neural Progenitor Cells in the Forebrain
Adult neural progenitor cells in the SVZ and hippocampus represent the most
thoroughly investigated and best characterized of such cells in the forebrain.
These progenitor cells are often detected in vivo through the use of retroviruses
(4) or thymidine autoradiography (5) . Recently, the thymidine analog bromo-
deoxyuridine (BrdU) has been used as a tracer of new DNA synthesis to label
dividing cells in the CNS (6) . There are advantages and disadvantages to these
methods (1) . The highest density of progenitor cells is found in the SVZ.
Neuronal progenitors in the SVZ migrate tangentially (sagittally) along the
rostral migratory stream into the olfactory bulb, where they differentiate into
granular and periglomerular neurons (7 , 8) . In contrast, glial progenitors in
the SVZ migrate radially into neighboring brain areas such as the striatum,
corpus callosum, and neocortex (9) . Adult neural progenitors in the hippocam-
pus are distributed throughout the medial dentate gyrus at all rostrocaudal
levels (10 , 11) . They are typically observed in a thin lamina between the hilus
and the granule cell layer, that is, the subgranular zone, as well as within the
granule cell layer and hilus (10 , 11) . Approximately half of newborn cells in
the hippocampus are believed to differentiate into neurons 3-4 wk after their