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Review Article

Neuroinflammatory modulators of

oligodendrogenesis

1,2
Ana Armada-Moreira 1,2* , Filipa F. Ribeiro 1,2* , Ana M. Sebastião , Sara Xapelli 1,2
1 Instituto de Farmacologia e Neurociências, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
2 Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.

ABSTRA CT

Oligodendrocytes are key neural cells that are responsible for producing myelin sheaths that wrap around neuronal axons in the central
nervous system. Myelin is essential to insulate neurons and maintain a fast and saltatory propagation of action potentials along the axon.
However, oligodendrocytes are very susceptible to damage, and thus demyelination may arise from a brain lesion or a neurodegenerative
disorder. Consequently, demyelination produces a loss of axonal insulation leading to sensory or motor neuron failure. During adulthood,
there are two main sources of oligodendrocytes: parenchymal oligodendrocyte precursor cells (OPCs) and subventricular zone derived
OPCs. In this review, we will discuss oligodendrogenesis derived from these two sources, and also highlight their main extrinsic and
intrinsic modulators. In addition, the neuroinflammatory mediators of oligodendrogenesis will also be assessed.

Key words: Demyelination, inflammation, neural stem cells, oligodendrocyte, remyelination

INTRODUCTION
formation. This process is called remyelination, one
of the few spontaneous processes of regeneration that
Oligodendrocytes are the myelin‑forming cells of the take place in the adult CNS. New oligodendrocyte
[3]
central nervous system (CNS). They are the last brain production is therefore enhanced in response to a
cells to be generated during development, making pathological insult such as demyelination. During the
myelination a late event in brain maturation. Their progression of a demyelinating disease, such as multiple
[1]
cholesterol‑rich membrane loops around neuronal sclerosis (MS), several inflammatory modulators
axons creating a myelin sheath, which is a multilamellar are released by a variety of brain cells impacting
spiral structure that protects neurons, ensures their the determination, proliferation, differentiation,
survival and provides electrical insulation that migration, and maturation of oligodendrocyte precursor
[1]
enables faster transmission of action potentials along cells (OPCs), ultimately resulting in remyelination.
axons. Oligodendrocytes are essential for proper New myelinating oligodendrocytes are derived from
[2]
brain functioning and are easily affected by oxidative two main cell sources: early postnatal‑derived OPCs
stress, so that demyelination is often a secondary that are present all over the brain parenchyma; and
[4]
event to brain lesions or pathologies. However, new new OPCs that are continuously originated from a
[1]
oligodendrocytes are continuously generated during distinct group of transit‑amplifying progenitors in the
adulthood, which restore insulation of demyelinated subventricular zone (SVZ) of the lateral walls of the
axons and/or remodel existing myelin, an important lateral ventricles. [4,5] In response to demyelination, both
role for functional plasticity, learning, and memory
parenchymal OPCs and SVZ‑derived OPCs produce
new oligodendrocytes to recover from myelin loss. [5]
*Authors contributed equally
Corresponding Author: Dr. Sara Xapelli, Oligodendrogenesis is a process that is regulated by
Instituto de Medicina Molecular, Faculdade de Medicina da
Universidade de Lisboa, Av. Professor Egas Moniz, extrinsic and intrinsic factors. The main external stimuli
1649‑028 Lisboa, Portugal. are morphogens, growth factors, and extracellular
E‑mail: sxapelli@medicina.ulisboa.pt
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Cite this article as: Armada-Moreira A, Ribeiro FF, Sebastião AM, Xapelli S.
DOI: Neuroinflammatory modulators of oligodendrogenesis. Neuroimmunol
10.4103/2347-8659.167311 Neuroinflammation 2015;2:263-73.
Received: 14-02-2015; Accepted: 15-06-2015

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