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Oligodendrocytes (), or oligodendroglia, are a type of
neuroglia Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...
whose main functions are to provide support and insulation to
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
s in the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
of jawed vertebrates, equivalent to the function performed by
Schwann cell Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensh ...
s in the
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...
. Oligodendrocytes do this by creating the
myelin sheath Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be l ...
. A single oligodendrocyte can extend its processes to 50 axons, wrapping approximately 1 μm of myelin sheath around each axon; Schwann cells, on the other hand, can wrap around only one axon. Each oligodendrocyte forms one segment of myelin for several adjacent axons. Oligodendrocytes are found only in the central nervous system, which comprises the
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
and
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
. These cells were originally thought to have been produced in the ventral neural tube; however, research now shows oligodendrocytes originate from the ventral ventricular zone of the embryonic spinal cord and possibly have some concentrations in the forebrain. They are the last cell type to be generated in the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
(CNS). Oligodendrocytes were discovered by
Pío del Río Hortega Pío del Río Hortega (1882 – 1945) was a Spanish neuroscientist who discovered microglia. Biography Río Hortega was born in Portillo, Valladolid on 5 May 1882. He studied locally and qualified to practice medicine in 1905. He obtained his do ...
.


Classification

Oligodendrocytes are a type of
glial cell Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...
. They arise during development from
oligodendrocyte precursor cell Oligodendrocyte progenitor cells (OPCs), also known as oligodendrocyte precursor cells, NG2-glia, O2A cells, or polydendrocytes, are a subtype of glia in the central nervous system named for their essential role as precursors to oligodendrocytes. ...
s (OPCs), which can be identified by their expression of a number of
antigens In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
, including the
ganglioside A ganglioside is a molecule composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (e.g. ''N''-acetylneuraminic acid, NANA) linked on the sugar chain. NeuNAc, an acetylated derivative of the carbohydrate si ...
GD3, the NG2 chondroitin sulfate proteoglycan, and the platelet-derived growth factor-alpha receptor subunit (PDGF-alphaR). Mature oligodendrocytes are broadly classified into either myelinating or non-myelinating satellite oligodendrocytes. Precursors and both mature types are typically identified by their expression of the transcription factor
OLIG2 Oligodendrocyte transcription factor (OLIG2) is a basic helix-loop-helix ( bHLH) transcription factor encoded by the ''Olig2'' gene. The protein is of 329 amino acids in length, 32 kDa in size and contains one basic helix-loop-helix DNA-binding do ...
.


Development

Most oligodendrocytes develop during
embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
and early postnatal life from restricted periventricular germinal regions. Oligodendrocyte formation in the adult brain is associated with glial-restricted
progenitor cell A progenitor cell is a Cell (biology), biological cell that can Cellular differentiation, differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor ...
s, known as
oligodendrocyte progenitor cell Oligodendrocyte progenitor cells (OPCs), also known as oligodendrocyte precursor cells, NG2-glia, O2A cells, or polydendrocytes, are a subtype of glia in the central nervous system named for their essential role as precursors to oligodendrocytes. ...
s (OPCs). SVZ cells migrate away from germinal zones to populate both developing white and gray matter, where they differentiate and mature into
myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...
-forming oligodendrocytes. However, it is not clear whether all oligodendrocyte progenitors undergo this sequence of events. Between midgestation and term birth in human cerebral white matter, three successive stages of the classic human oligodendrocyte lineage are found: OPCs, immature oligodendrocytes (non-myelinating), and mature oligodendrocytes (myelinating). It has been suggested that some undergo
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
and others fail to differentiate into mature oligodendrocytes but persist as adult OPCs. Remarkably, oligodendrocyte population originated in the
subventricular zone The subventricular zone (SVZ) is a region situated on the outside wall of each lateral ventricle of the vertebrate brain. It is present in both the embryonic and adult brain. In embryonic life, the SVZ refers to a secondary proliferative zone ...
can be dramatically expanded by administering
epidermal growth factor Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-k Da and has 53 amino acid residues and three intramolecular disulfide bonds. EGF was originally descr ...
(EGF).


Function


Myelination

Mammalian
nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
s depend crucially on myelin sheaths, which reduce ion leakage and decrease the capacitance of the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
, for rapid signal conduction. Myelin also increases impulse speed, as saltatory propagation of
action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
s occurs at the
nodes of Ranvier In neuroscience and anatomy, nodes of Ranvier ( ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, al ...
in between
Schwann cells Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensh ...
(of the PNS) and oligodendrocytes (of the CNS). Furthermore, impulse speed of myelinated axons increases linearly with the axon diameter, whereas the impulse speed of unmyelinated cells increases only with the square root of the diameter. The insulation must be proportional to the diameter of the fibre inside. The optimal
ratio In mathematics, a ratio shows how many times one number contains another. For example, if there are eight oranges and six lemons in a bowl of fruit, then the ratio of oranges to lemons is eight to six (that is, 8:6, which is equivalent to the ...
of axon diameter divided by the total fiber diameter (which includes the myelin) is 0.6. Myelination is only prevalent in a few brain regions at birth and continues into adulthood. The entire process is not complete until about 25–30 years of age. Myelination is an important component of intelligence, and white matter quantity may be positively correlated with IQ test results in children. Rats that were raised in an enriched environment, which is known to increase cognitive flexibility, had more myelination in their corpus callosi.


Metabolic support

Oligodendrocytes interact closely with nerve cells and provide trophic support by the production of glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), or insulin-like growth factor-1 (IGF-1). They may also directly provide metabolites to neurons, as described by the lactate shuttle hypothesis. It is hypothesized that satellite oligodendrocytes (or perineuronal oligodendrocytes) are functionally distinct from other oligodendrocytes. They are not attached to neurons via myelin sheaths and, therefore, do not contribute to insulation. They remain opposed to neurons and regulate the extracellular fluid. Satellite oligodendrocytes are considered to be a part of the grey matter whereas myelinating oligodendrocytes are a part of the white matter. They may support neuronal metabolism. Satellite oligodendrocytes may be recruited to produce new myelin after a demyelinating injury.


Clinical significance

Diseases that result in injury to oligodendrocytes include demyelinating diseases such as
multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
and various
leukodystrophies Leukodystrophies are a group of usually inherited disorders characterized by degeneration of the white matter in the brain. The word ''leukodystrophy'' comes from the Greek roots ''leuko'', "white", ''dys'', "abnormal" and ''troph'', "growth". Th ...
. Trauma to the body, e.g. spinal cord injury, can also cause demyelination. The immature oligodendrocytes, which increase in number during mid-
gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregna ...
, are more vulnerable to hypoxic injury and are involved in
periventricular leukomalacia Periventricular leukomalacia (PVL) is a form of white-matter brain injury, characterized by the necrosis (more often coagulation) of white matter near the lateral ventricles. It can affect newborns and (less commonly) fetuses; premature infan ...
. This largely congenital condition of damage to the newly forming brain can therefore lead to
cerebral palsy Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, stiff muscles, weak muscles, and tremors. There may be problems with sensa ...
. In cerebral palsy, spinal cord injury, stroke and possibly multiple sclerosis, oligodendrocytes are thought to be damaged by excessive release of the
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...
,
glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
.Káradóttir et al., 2007 Damage has also been shown to be mediated by
N-methyl-D-aspartate receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and ...
s. Oligodendrocyte dysfunction may also be implicated in the
pathophysiology Pathophysiology ( physiopathology) – a convergence of pathology with physiology – is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is the ...
of
schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
and
bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
. Oligodendrocytes are also susceptible to infection by the
JC virus ''Human polyomavirus 2'', commonly referred to as the JC virus or John Cunningham virus, is a type of human polyomavirus (formerly known as papovavirus). It was identified by electron microscopy in 1965 by ZuRhein and Chou, and by Silverman and ...
, which causes progressive multifocal leukoencephalopathy (PML), a condition that specifically affects white matter, typically in
immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
patients.
Tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s of oligodendrocytes are called
oligodendroglioma Oligodendrogliomas are a type of glioma that are believed to originate from the oligodendrocytes of the brain or from a glial precursor cell. They occur primarily in adults (9.4% of all primary brain and central nervous system tumors) but are also ...
s. The chemotherapy agent Fluorouracil (5-FU) causes damage to the oligodendrocytes in mice, leading to both acute
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
(CNS) damage and progressively worsening delayed degeneration of the CNS.


See also

*
White matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribution ...
*
Schwann cells Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensh ...
* 2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNPase) *
List of human cell types derived from the germ layers This is a list of cells in humans derived from the three embryonic germ layers – ectoderm, mesoderm, and endoderm. Cells derived from ectoderm Surface ectoderm Skin * Trichocyte * Keratinocyte Anterior pituitary * Gonadotrope * Corticotro ...


References

;Bibliography *Raine, C.S. (1991). Oligodendrocytes and central nervous system myelin. In Textbook of Neuropathology, second edition, R.L. Davis and D.M. Robertson, eds. (Baltimore, Maryland: Williams and Wilkins), pp. 115–141. * * * * *


External links

* The Department of Neuroscience at
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{{Authority control Glial cells Biology of bipolar disorder