Review articleOligodendrogliopathy in neurodegenerative diseases with abnormal protein aggregates: The forgotten partner
Section snippets
Oligodendrocytes: general aspects
In addition to neurons and astrocytes, other cells, smaller in size, are present in the nervous system. These cells, called the “third element” turned out to be two different cell types after pioneering studies by Del Rio-Hortega (1921); one of these was microglia, the other oligodendroglia. The two cell types have different origins, morphology and functions; processes in some subtypes of oligodendroglial cells run in parallel to myelin thus suggesting a relationship between oligodendroglia and
Development of oligodendroglia and myelin
Oligodendrocyte precursor cells (OPCs) proliferate in the neuroepithelium of the subventricular zone and migrate to the future white matter through extending and retracting cell processes until their definitive placements (Baumann and Pham-Dinh, 2001; Kirby et al., 2006; Miller and Mi, 2007; Hughes et al., 2013). This process is modulated by self-repulsive movements which allow a certain separation between neighboring cells (Jarjour et al., 2003; Hughes et al., 2013). Oligodendrocytes during
Diversity of OPCs/NG2-glia
OPCs are also called NG2-glia because of their expression of proteoglycan GSPG4 (NG2). These cells are not only found during the development of the nervous system; OPCs are present in the adult brain and show particular features distinct from those seen in embryonic OPCs (Káradóttir et al., 2008; Tripathi et al., 2011; Clarke et al., 2012; Vigano et al., 2013; Crawford et al., 2016). OPCs/NG2-glia is considered the fourth element in the adult central nervous system constituting about 5–10% of
Expression of neurotransmitter, hormone receptors and ion channels in oligodendrocyte lineage
A plethora of neurotransmitter and other receptors are expressed in OPCs and at different stages of oligodendroglial differentiation and maturation; these modulate, after specific ligand binding, various stages of oligodendrocyte development (Marinelli et al., 2016). GABAB receptors are expressed at early stages and their activation induces proliferation and migration of OPCs (Luyt et al., 2007). NMDA, AMPA and kainate receptors are expressed in immature and myelinating oligodendrocytes
Diversity of oligodendrocytes
Transcriptomic profiles of neurons, astrocytes and oligodendroglia have been identified using high-throughput methods (Cahoy et al., 2008; Zhang et al., 2014; Moyon et al., 2015; van Bruggen et al., 2017). Single-cell RNA sequencing revealed different subpopulations of oligodendrocytes from several brain regions of juvenile and adult mouse brain (Zeisel et al., 2015; Marques et al., 2016). A single cluster of OPCs was found in the first studies (Marques et al., 2016; Hochgerner et al., 2017).
Signals involved in OPC generation, oligodendroglia differentiation and myelination
Major knowledge of OPC generation comes from the study of the mouse spinal cord and forebrain. In the spinal cord, the first wave of generation occurs at embryonic day 12, originates from the ventral neural tube and depends upon sonic hedgehog (SHH) and Nkx6.1 and Nkx6.2 regulation of Olig 1 and Olig2 transcription (Orentas et al., 1999; Lu et al., 2000; Vallstedt et al., 2005). A second wave originates at embryonic day 15 from the dorsal spinal cord; it is not dependent on SHH but it is
Oligodendroglia and axon integrity
In addition to studies showing the role of axons in the development of oligodendroglia, several in vitro and in vivo experimental models have demonstrated that oligodendroglia are involved in support of axonal transport and axon integrity (Nave and Trapp, 2008; Lee et al., 2012; Saab et al., 2013; Beirowski, 2013; Morrison et al., 2013; White and Krämer-Albers, 2014; Simons et al., 2016). Axon outgrowth is also sustained in part by growth factors such as GDNF and BDNF produced by
Oligodendrocytes in brain aging
Human myelination is uniquely expanded and vulnerable to aging (Tse and Herrup, 2017). White matter lucencies with age were discovered by neuroimaging studies (Hachinski et al., 1987; Meyer et al., 1992). Progressive white matter decline in human brain, as revealed by magnetic resonance imaging (MRI), starts at about 45 years of age (Bartzokis et al., 2001, 2003; Sperling et al., 2014) and it is enhanced in Alzheimer’s disease (Bartzokis et al., 2003). This is accompanied by white matter
Oligodendrogliopathy
The term astrogliopathy refers to alterations of astrocytes occurring in diseases of the nervous system, includes reactive astrogliosis (mainly manifested as an increase in the amount of GFAP and in the number of astrocytes containing GFAP), and stresses the cardinal role of astrocytic dysfunction in the pathogenesis of neurological diseases (Seifert et al., 2006; Pekny and Pekna, 2014; Pekny et al., 2016; Osborn et al., 2016; Verkhratsky et al., 2017a, b). Astrocytopathy refers to decrease in
Final comments
There is extensive information about the structure and function of oligodendrocytes, oligodendroglial precursors, diversity of precursors and adult oligodendroglial cells, signaling pathways modulating maturation and development of myelinating cells, interactions of oligodendrocytes and neurons and astrocytes, and participation of oligodendrocytes in energy metabolism, as well as maintenance of axon integrity and the normal functioning of the central nervous system. Oligodendrocytes can be
Conflict of interests
No relevant data.
Acknowledgements
Part of this work was supported by the Ministry of Economy and Competitiveness, Institute of Health Carlos III (co-funded by European Regional Development Fund, ERDF, a way to build Europe) FIS PI17/00809, and co-finanzed by ERDF under the program Interreg Poctefa: RedPrion 148/16. I wish to thank Margarita Carmona, Benjamín Torrejón-Escribano and Daniela Diaz-Lucena for technical assistance, and T. Yohannan for editorial help.
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