Oligodendrocytes are found exclusively in the CNS, which comprises thebrain andspinal cord. They are the most widespread cell lineage, includingoligodendrocyte progenitor cells, pre-myelinating cells, and mature myelinating oligodendrocytes in the CNSwhite matter.[3] Non-myelinating oligodendrocytes are found in thegrey matter surrounding and lying next to neuronal cell bodies. They are known as neuronal satellite cells, and their presence is not understood.[2]
It was once thought that oligodendrocytes were produced in the ventralneural tube, theembryonic precursor to the CNS. Studies have suggested that they originate from the ventralventricular zone of the embryonicspinal cord, with some potential concentrations in theforebrain.[4] Oligodendrocytes are the last type of cell to be generated in the CNS.[5] Oligodendrocytes were discovered byPío del Río Hortega.[6][7]
Most oligodendrocytes develop duringembryogenesis and early postnatal life from restricted periventricular germinal regions.[14] Oligodendrocyte formation in the adult brain is associated with glial-restrictedprogenitor cells, known asoligodendrocyte progenitor cells (OPCs).[15]Subventricular zone OPCs are activated and then migrate away fromgerminal[15] zones to populate both developingwhite andgray matter, where they differentiate and mature into myelin-forming oligodendrocytes.[11][16] However, it is not clear whether all oligodendrocyte progenitors undergo this sequence of events.[17]
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).[18] It has been suggested that some undergoapoptosis[19] and others fail to differentiate into mature oligodendrocytes but persist as adult OPCs.[20] Remarkably, oligodendrocyte population originated in the subventricular zone can be dramatically expanded by administeringepidermal growth factor (EGF).[21][22]
Mammaliannervous systems depend crucially on myelin sheaths, which reduce ion leakage and decrease the capacitance of thecell membrane, for rapid signal conduction.[23] Myelin also increases impulse speed, assaltatory conduction ofaction potentials occurs at thenodes of Ranvier in oligodendrocytes. The impulse speed of a myelinated axon 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 of axon diameter divided by the total fiber diameter (which includes the myelin) is 0.6.[24]
Oligodendrocytes in rat cerebellum stained with antibody tomyelin basic protein in red and for DNA in blue. Two oligodendrocyte cell bodies are clearly visible as well as several myelinated axons. These are hollow tubes and so appear as "tramlines" in this confocal image. Most of the DNA is in the nuclei ofcerebellum granule cells, which are smallinterneurons. Image and antibody stain fromEnCor Biotechnology Inc.
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.[24] Myelination is an important component of intelligence, and white matter quantity may be positively correlated with IQ test results in children.[24] Rats that were raised in an enriched environment, which is known to increasecognitive flexibility, had more myelination in theircorpus callosum.[25]
Oligodendrocytes, best known for their role in myelinating axons in the central nervous system, also have important functions in immune regulation.[26] These cells can influence the immune environment by secreting cytokines and chemokines, which modulate the activity of various immune cells. Oligodendrocytes express receptors that allow them to respond to inflammatory signals, thereby participating in the brain's defense mechanisms. Additionally, they play a role in maintaining the blood-brain barrier and can contribute to the resolution of inflammation, highlighting their multifaceted role in both neural maintenance and immune responses.[26][27] While most research has focused on the immune functions ofOPCs,[27][26] it is believed that oligodendrocytes themselves still possess significant immune functions.[26]
It is hypothesized thatsatellite oligodendrocytes (orperineuronal 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 theextracellular fluid.[32] 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.[33]
Diseases that result in injury to oligodendrocytes include demyelinating diseases such asmultiple sclerosis and variousleukodystrophies. Trauma to the body, e.g. spinal cord injury, can also cause demyelination. The immature oligodendrocytes, which increase in number during mid-gestation, are more vulnerable tohypoxic injury and are involved inperiventricular leukomalacia.[34] This largely congenital condition of damage to the newly forming brain can therefore lead tocerebral palsy. In cerebral palsy, spinal cord injury, stroke and possibly multiple sclerosis, oligodendrocytes are thought to be damaged by excessive release of theneurotransmitter,glutamate.[35] Damage has also been shown to be mediated byN-methyl-D-aspartate receptors.[35] Oligodendrocyte dysfunction may also be implicated in thepathophysiology ofschizophrenia andbipolar disorder.[36]
Oligodendrocytes are also susceptible to infection by theJC virus, which causesprogressive multifocal leukoencephalopathy (PML), a condition that specifically affects white matter, typically inimmunocompromised patients. The chemotherapy agentFluorouracil (5-FU) causes damage to the oligodendrocytes in mice, leading to both acutecentral nervous system (CNS) damage and progressively worsening delayed degeneration of the CNS.[37][38]DNA methylation may also have a role in the degeneration of oligodendrocytes.[39]
Damage to myelin has been shown to exacerbateamyloid plaque accumulation, potentially placing age-related myelin decline as an upstream risk factor inAlzheimer's disease.[40] Oligodendrocytes also abundantly express components of the amyloidogenic pathway,[41][42][43] produce amyloid beta (Aβ), and contribute to plaque burden,[42][43] which is relevant when considering therapeutic interventions for Alzheimer's disease.
The neuronal satellite cells in the grey matter of the lobes of the brain, can produce slow-growingtumours. The tumours known asoligodendrogliomas are of clusters of tumour cells beneath thepia mater.[2]
^abCarlson N (2010).Physiology of Behavior. Boston, MA: Allyn & Bacon. pp. 38–39.ISBN978-0-205-66627-0.
^abcdHaines DE, Mihailoff GA (2018).Fundamental neuroscience for basic and clinical applications (5th ed.). Philadelphia: Elsevier. pp. 28–31.ISBN978-0-323-39632-5.
^Curtis R, Cohen J, Fok-Seang J, Hanley MR, Gregson NA, Reynolds R, et al. (February 1988). "Development of macroglial cells in rat cerebellum. I. Use of antibodies to follow early in vivo development and migration of oligodendrocytes".Journal of Neurocytology.17 (1):43–54.doi:10.1007/BF01735376.PMID3047324.
^LeVine SM, Goldman JE (November 1988). "Ultrastructural characteristics of GD3 ganglioside-positive immature glia in rat forebrain white matter".The Journal of Comparative Neurology.277 (3):456–464.doi:10.1002/cne.902770310.PMID3198802.
^abHardy R, Reynolds R (April 1991). "Proliferation and differentiation potential of rat forebrain oligodendroglial progenitors both in vitro and in vivo".Development.111 (4):1061–1080.doi:10.1242/dev.111.4.1061.PMID1879350.
^Pringle NP, Mudhar HS, Collarini EJ, Richardson WD (June 1992). "PDGF receptors in the rat CNS: during late neurogenesis, PDGF alpha-receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage".Development.115 (2):535–551.doi:10.1242/dev.115.2.535.PMID1425339.
^Levison SW, Goldman JE (February 1993). "Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain".Neuron.10 (2):201–12.doi:10.1016/0896-6273(93)90311-e.PMID8439409.
^Franklin RJ, Ffrench-Constant C (November 2008). "Remyelination in the CNS: from biology to therapy".Nature Reviews. Neuroscience.9 (11):839–855.doi:10.1038/nrn2480.PMID18931697.
^Barres BA, Hart IK, Coles HS, Burne JF, Voyvodic JT, Richardson WD, et al. (November 1992). "Cell death in the oligodendrocyte lineage".Journal of Neurobiology.23 (9):1221–1230.doi:10.1002/neu.480230912.PMID1469385.
^Bradl M, Lassmann H (January 2010)."Oligodendrocytes: biology and pathology".Acta Neuropathologica.119 (1):37–53.doi:10.1007/s00401-009-0601-5.PMC2799635.PMID19847447....oligodendrocytes can provide trophic support for neurons by the production of glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), or insulin-like growth factor-1 (IGF-1).
^Baumann N, Pham-Dinh D (April 2001). "Biology of oligodendrocyte and myelin in the mammalian central nervous system".Physiological Reviews.81 (2):871–927.doi:10.1152/physrev.2001.81.2.871.PMID11274346.
^Kinney HC, Back SA (September 1998). "Human oligodendroglial development: relationship to periventricular leukomalacia".Seminars in Pediatric Neurology.5 (3):180–189.doi:10.1016/s1071-9091(98)80033-8.PMID9777676.
^Tkachev D, Mimmack ML, Ryan MM, Wayland M, Freeman T, Jones PB, et al. (September 2003). "Oligodendrocyte dysfunction in schizophrenia and bipolar disorder".Lancet.362 (9386):798–805.doi:10.1016/S0140-6736(03)14289-4.PMID13678875.S2CID7511585.
Raine CS (1991). "Oligodendrocytes and central nervous system myelin.". In Davis RL, Robertson DM (eds.).Textbook of Neuropathology (second ed.). Baltimore, Maryland: Williams and Wilkins. pp. 115–141.
