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Morphology, Functions and Involvement in Neurodegenerative Diseases

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Morphology, Functions and Involvement in Neurodegenerative Diseases Med. Weter. 2019, 75 (8), 465-471 DOI: dx.doi.org/10.21521/mw.6258 465 Artykuł przeglądowy Review Oligodendrocytes: Morphology, functions and involvement in neurodegenerative diseases IZABELA KRAWCZYK-MARĆ, AGATA WAWRZYNIAK, IWONA ŁUSZCZEWSKA-SIERAKOWSKA*, MAREK BABICZ**, STANISŁAW ORKISZ Department of Morphological Sciences, Faculty of Medicine, University of Rzeszów, ul. Leszka Czarnego 4, 35-615 Rzeszów, Poland *Department of Human Anatomy, Medical University of Lublin, ul. Jaczewskiego 4, 20-090 Lublin, Poland **Department of Pig Breeding and Production Technology, Faculty of Biology, Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, ul. Akademicka 13, 20-950 Lublin, Poland Received 31.10.2018 Accepted 17.01.2019 Krawczyk-Marć I., Wawrzyniak A., Łuszczewska-Sierakowska I., Babicz M., Orkisz S. Oligodendrocytes: morphology, functions and involvement in neurodegenerative diseases Summary Oligodendrocytes (OLs) are myelinating cells of the central nervous system (CNS). They are a highly specialized type of glial cell in the CNS of vertebrates, which guarantee the transmission of action potentials over long distances by producing a myelin sheath that wraps adjacent axons. Although they are often credited merely with participation in myelination, recent research has led to a radical change in the understanding the role of these glial cells. OLs are currently understood to be plastic and adaptive cells, capable of responding quickly to changes taking place in the spatial neuronal network in the CNS. Due to their complex differentiation process and their physiology, OLs are among the most sensitive cells in the CNS. Finding answers about their interactions with other types of glial cells may result in benefits in the form of neuroprotection and axon plasticity. Damage to OLs and the myelin sheath is one of processes contributing to the development of crippling neurological diseases, although the role of these cells in neurodegeneration remains controversial. This article not only presents OLs as cells whose ultimate goal is to produce myelin sheaths, but also discusses their involvement in neurodegenerative diseases. Keywords: oligodendrocytes, central nervous system, myelin, neurodegenerative diseases The nervous system of humans and animals consists sified less than 100 years ago by Pio del Rio-Hortega, of two main cell types: neurons and neuroglia (21, who correctly assumed that microglia play a defensive 48). Research on the neuroglia has contributed to the role in a pathological CNS (39). Although that research understanding of interactions between neurons and was remarkably accurate for that time, innovative tech- glial cells. An important feature of neuroglial cells is nologies have revealed new molecular, cellular and their excitability, which enables communication with physiological aspects of glial tissue in the CNS. In the neurons and modulates their activity (5). Neurons, normal CNS, astrocytes regulate neurotransmitters and glia and blood vessels work closely together to control neurovascular dynamics. In response to damage, they conduction functions. Impairment of this symbiosis become reactive and, together with the microglia, form results in neurodegenerative diseases involving cogni- glial scars. Under the influence of infection or damage tive dysfunctions, such as Alzheimer’s disease (AD) in the CNS, microglia promote axon growth and remy- (52). The central nervous system (CNS) of an adult elination, but in the case of excessive activity, they exert mammal includes four types of glial cells: astrocytes, a cytotoxic effect. OLs and their precursors in normal oligodendrocytes (OLs), microglial cells and ependymal tissue accelerate axonal conduction and support axonal glia (9). OLs, astrocytes and ependymocytes are derived function, but they are extremely susceptible to damage. from a common line of neuronal progenitor cells in the Astrocytes, microglia and OLs interact to influence the neuroectoderm, whereas microglial cells are CNS mac- survival, differentiation and remyelination of neurons. rophages derived from monocytes (42). In the peripheral Communication between glial cells and nerve fibres nervous system, glial cells are represented by Schwann is present even in invertebrates, such as earthworms, cells and satellite glial cells (21). Glial cells were clas- shrimp and copepods, but OLs and Schwann cells that 466 Med. Weter. 2019, 75 (8), 465-471 produce myelin sheaths are present only in vertebrates origin, such as pro-inflammatory cytokines, growth fac- (29). In vertebrates, the ratio of glial cells to neurons in tors, complement system proteins, free radicals, neuro- the cortex increases with increasing brain size. Various toxins, nitric oxide, prostaglandins, ATP or stimulating authors have reported that the ratio of the number of amino acids. Activated microglia can secrete numerous neuroglia to neurons in the cerebral cortex is approxi- growth and inflammatory factors. These glia maintain mately 1.5-1.7 in humans, 0.3-0.4 in rodents, 1.1 in the homeostasis of the neuronal microenvironment, cats, 1.2 in horses, 0.5-1.0 in Rhesus monkeys, and supervise the survival of neurons within the CNS and 4.0-6.0 in elephants and whales (Balaenoptera physa- act as immunologically competent cells (23). lus). The highest number of glial cells has been found in the cerebral cortex of dwarf whales (Balaenoptera Oligodendrocytes acutorostrata), which contains about 12.8 billion neu- In the CNS, OLs are glial cells responsible for the pro- rons and about 98 billion glial cells. In this case, the duction of myelin. It is easy to forget that until the mid- ratio of the number of glia to neurons is 7.6 (56). The 1950s, many researchers believed the myelin sheath increase in the ratio of the number of neuroglia to neu- to be an axonal product, not a natural glial product. rons during the evolution of mammals is a reflection of Neuroglia were often perceived only as ‘glue’, whose the increase in energy expenditure by neurons. Human role was limited to supporting neurons. Only recently neurons need about 3.3 times as much energy as rodent have scientists begun to analyse and understand this neurons do (26). unique type of glial cell. Advances in imaging technol- ogy and model systems have provided researchers with Astrocytes access to the internal mechanisms of OLs, allowing Astrocytes are specialized CNS glial cells that per- them to investigate their role in axonal maintenance, form many functions. They are presumed to be formed survival and adaptation (14, 15, 25, 54), as well as in indirectly from radial glia, whose functions include cre- the formation of a complex spatial network of neuronal ating scaffolding for newly formed neurons. Astrocytes circuits (28). have a star-shaped cellular body with numerous Formation of oligodendrocytes. In vertebrates, the branched processes. On the basis of morphological dif- CNS myelination process begins during embryogenesis ferences, astrocytes have been divided into two main and continues after birth, with the time of its completion classes: protoplasmic astrocytes (with short processes), depending on the species of animal. In the initial stage present mainly in the grey matter of the CNS, and of the neural tube, there is only one cell layer built of fibrous astrocytes (with many long processes), located neuroblasts. This gives rise to neurons and spongio- primarily in the white matter (9, 49). Astrocytes are blasts, from which the remaining types of glial cells additionally classified according to their ability to react are formed, with the exception of microglia (12). The to CNS damage. Inactive, resting and reactive astrocytes formation of OLs begins with O-2A (oligodendrocyte- have been distinguished. The resting type is present in type 2 astrocyte) bipotential glial precursor cells, from normal, unchanged glial tissue in the CNS, while reac- which all types of glia may develop. O-2A migrate tive astrocytes locate closer to the site of injury, and very quickly and inhabit the white and grey matter of together with microglia participate in the formation of the CNS. During this migration, some of O-2A become glial scars (32). precursor cells for OLs – oligodendrocyte precursor/ progenitor cells (OPCs) (17). These cells show a high Microglia level of ganglioside recognition by the A2B5 antibody, Microglia are a population of resident mesenchymal the PDGF α receptor (PDGFαR) and the NG2 proteo- CNS macrophages located near nervous structures and glycan. Most OPCs proliferate in the CNS white matter closely involved in brain homeostasis. This type of glial in response to local mitogenic signals. Differentiation cells also plays a key role in the development and differ- of OPCs is regulated in part by transcription factors, entiation of neurons and in perinatal synapse formation. such as Olig1, Olig2, Mash, Myt1, Nkx2.2 and Sox10. In the adult brain, microglial cells account for about Before birth, stem cells stop proliferating, which slows 5-20% of all glial cells (1). They take the form of typi- down the cell cycle associated with the growth, differ- cal macrophages that multiply during inflammation or entiation and death of the cell. At the target site, OPCs local damage to nervous tissue. They have a small oval are transformed into immature OLs, characterized by cell body (about 4 µm) with numerous processes. CNS the expression of monoclonal antibody O4. Cells with disorders caused by factors such as infection, trauma this antibody are transformed into
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