Page 273 - Read Online

After CNS development, a small fraction of OPCs matter OPCs. What is the role of OPCs in gray matter
remains undifferentiated, in an immature slowly remains a question to be explored.
proliferative or quiescent state. [17] These adult OPCs
are morphologically equivalent and express the same In response to a demyelinating insult, the remyelitation
markers as the OPCs present during development. [18] process is activated. New myelinating oligodendrocytes
However, they differ from the developing OPCs in are mainly generated from early postnatal‑derived OPCs
[4]
growth factor responsiveness, migration capacity, and that are present in the brain parenchyma. In a first
cell cycle length. [19‑21] Their cell density, although phase, quiescent or slow‑dividing OPCs are recruited
stable throughout adult life, is higher in white matter to the damaged areas OPCs start to proliferate, migrate,
than in gray matter. [22,23] Indeed, it has been shown and populate the demyelinated area. In a second phase,
that adult OPCs present a higher rate of proliferation the recruited OPCs start to differentiate into mature
in white matter, which is a possible explanation oligodendrocytes as they form myelin sheaths around
for the difference in cell density. [22] It is possible to demyelinated axons. [29] Oligodendrocytes derived
further divide white matter OPCs and gray matter from parenchymal OPCs are only able to migrate
OPCs by their characteristics. While white matter short distances, just populating damaged areas in the
OPCs are proliferative and eventually lead to adult proximity of their progenitor cells. [5]
oligodendrogenesis, gray matter OPCs remain quiescent
and immature. [22] OLIGODENDROGENESIS DERIVED FROM
ADULT SUBVENTRICULAR ZONE NEURAL STEM
Given these findings, could adult OPCs be a CELLS
heterogeneous population, possibly with several
distinct functions? Some studies show that the different After birth, OPCs can be produced by adult neural stem
characteristics observed in adult OPCs can be the cells (NSC), which are self‑renewing, multipotent cells
result of environmental signals. Specifically, gray that generate most of the cells of the nervous system, such
matter environment is described as an inhibitor of OPC as neurons, astrocytes, and oligodendrocytes. These
[30]
proliferation and differentiation while white matter NSCs can divide in three different ways: symmetrically,
environment seems to favor OPC maturation. [17,22,23] originating in two new NSCs (expansion, symmetrical
These differences may be linked to intrinsic cell self‑renewal); asymmetrically, originating one NSC and
mechanisms or to environmental cues. While there one differentiated cell (maintenance, asymmetrical
seem to be differences in the local microenvironment self‑renewal); or symmetrically, originating two
surrounding OPCs in white and gray matter, the differentiated cells (extinction, symmetrical commitment).
different characteristics of white matter and gray Depending on the activation of specific signaling
matter OPCs can also be explained by intrinsic pathways and the presence of differentiation‑inducing
mechanisms, such as receptor desensitization. For molecules, NSCs are capable of differentiating into cells of
instance, it is known that, in the developing spinal neuronal (neurogenesis) and glial (gliogenesis) lineages,
cord, PDGF‑A mRNA has higher expression in the particularly oligodendrocytes (oligodendrogenesis). [31]
gray matter, [24] which can lead to desensitization of
the receptor (PDGFRα) and prolonged impairment of Neural stem cells exist in discrete regions of the
gray matter OPCs maturation. [25] However, there are adult mammalian brain where neurogenesis and
indeed molecular differences between white matter oligodendrogenesis are highly regulated. [32] The brain
OPCs and gray matter OPCs, namely in the resting regions where these processes take place, that is
membrane potential and ion channels expression. [26,27] where the NSC pools can be encountered, are called
Concerning the ion channels, two subpopulations neurogenic niches. In adulthood, there are two main
of adult OPCs have been described: one completely neurogenic niches in the brain: the SVZ of the lateral
devoid of voltage‑gated Na channels, and another with ventricles, and the subgranular zone of the dentate
+
functional channels, able to react to action potentials. gyrus (DG) of the hippocampus. [33]
Consequently, this second subtype can sense neuronal
activity through axonal input and is more sensitive to In the SVZ, the NSC pool comprises type B cells, which
ischemia. [26] Another study corroborating the existence are quiescent NSCs that originate type C cells, which are
[34]
of functionally different subtypes shows that white fast dividing transient amplifying cells. Most of these
matter OPCs can generate myelinating oligodendrocytes C cells will then differentiate into neuroblasts (type A
[35]
even if they are transplanted into other brain regions. cells), migrate along the rostral migratory stream to
Gray matter OPCs, in contrast, remain less efficient the olfactory bulb, and terminally differentiate into
even if transplanted into white matter. [28] Therefore, interneurons. [36,37] SVZ‑derived oligodendrogenesis
it seems that white matter OPCs are more prepared to originates from a minority of C cells that do not follow
generate new myelinating oligodendrocytes than gray the previously explained cellular fate. Instead, they

264 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015 265