scholarly journals The contribution of oligodendrocytes and oligodendrocyte progenitor cells to central nervous system repair in multiple sclerosis: perspectives for remyelination therapeutic strategies

2017 ◽  
Vol 12 (12) ◽  
pp. 1939 ◽  
Author(s):  
AdrianaOctaviana Dulamea
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Therapeutic Strategies ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Central Nervous System Repair

scholarly journals mTORC2 loss in oligodendrocyte progenitor cells results in regional hypomyelination in the central nervous system

2022 ◽  
Author(s):  
Kristin D Dahl ◽  
Hannah A Hathaway ◽  
Adam R Almeida ◽  
Jennifer Bourne ◽  
Tanya L Brown ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Corpus Callosum ◽  
Signaling Pathways ◽  
Progenitor Cells ◽  
Myelin Proteins ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
The Central Nervous System

In the central nervous system (CNS), oligodendrocyte progenitor cells (OPCs) differentiate into mature oligodendrocytes to generate myelin, which is essential for normal nervous system function. OPC differentiation is driven by signaling pathways such as mTOR (Mechanistic Target of Rapamycin), which functions in two distinct complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), containing Raptor or Rictor respectively. In the current studies, mTORC2 signaling was selectively deleted from OPCs in PDGFRα-Cre X Rictorfl/fl mice. This study examined developmental myelination in male and female mice, comparing the impact of mTORC2 deletion in the corpus callosum and spinal cord. In both corpus callosum and spinal cord, Rictor loss in OPCs resulted in early reduction in myelin RNAs and some myelin proteins. However, these deficits rapidly recovered in spinal cord, where normal myelin abundance and thickness was noted at post-natal day 21 and 1.5 months. By contrast, the losses in corpus callosum resulted in severe hypomyelination, and increased unmyelinated axons. The current studies focus on uniquely altered signaling pathways following mTORC2 loss in developing oligodendrocytes. A major mTORC2 substrate is phospho-Akt-S473, which was significantly reduced throughout development in both corpus callosum and spinal cord at all ages measured, yet this had little impact in spinal cord. Loss of mTORC2 signaling resulted in decreased expression of actin regulators such as gelsolin in corpus callosum, but only minimal loss in spinal cord. The current study establishes a regionally-specific role for mTORC2 signaling in OPCs, particularly in the corpus callosum.

scholarly journals Glial Patchwork: Oligodendrocyte Progenitor Cells and Astrocytes Blanket the Central Nervous System

2022 ◽  
Vol 15 ◽  
Author(s):  
Heather M. Barber ◽  
Maria F. Ali ◽  
Sarah Kucenas
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Developmental Process ◽  
Emergent Behavior ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Cellular Behaviors ◽  
The Central Nervous System ◽  
Impact Injury

Tiling is a developmental process where cell populations become evenly distributed throughout a tissue. In this review, we discuss the developmental cellular tiling behaviors of the two major glial populations in the central nervous system (CNS)—oligodendrocyte progenitor cells (OPCs) and astrocytes. First, we discuss OPC tiling in the spinal cord, which is comprised of the three cellular behaviors of migration, proliferation, and contact-mediated repulsion (CMR). These cellular behaviors occur simultaneously during OPC development and converge to produce the emergent behavior of tiling which results in OPCs being evenly dispersed and occupying non-overlapping domains throughout the CNS. We next discuss astrocyte tiling in the cortex and hippocampus, where astrocytes migrate, proliferate, then ultimately determine their exclusive domains by gradual removal of overlap rather than sustained CMR. This results in domains that slightly overlap, allowing for both exclusive control of “synaptic islands” and astrocyte-astrocyte communication. We finally discuss the similarities and differences in the tiling behaviors of these glial populations and what remains unknown regarding glial tiling and how perturbations to this process may impact injury and disease.

scholarly journals Sera from Patients with NMOSD Reduce the Differentiation Capacity of Precursor Cells in the Central Nervous System

2021 ◽  
Vol 22 (10) ◽  
pp. 5192
Author(s):  
Ulises Gómez-Pinedo ◽  
Yolanda García-Ávila ◽  
Lucía Gallego-Villarejo ◽  
Jordi A. Matías-Guiu ◽  
María Soledad Benito-Martín ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Neuromyelitis Optica ◽  
Subventricular Zone ◽  
Precursor Cells ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Differentiation Capacity ◽  
The Central Nervous System

Introduction: AQP4 (aquaporin-4)–immunoglobulin G (IgG)-mediated neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that affects the central nervous system, particularly the spinal cord and optic nerve; remyelination capacity in neuromyelitis optica is yet to be determined, as is the role of AQP4–IgG in cell differentiation. Material and Methods: We included three groups—a group of patients with AQP4–IgG-positive neuromyelitis optica, a healthy group, and a sham group. We analyzed differentiation capacity in cultures of neurospheres from the subventricular zone of mice by adding serum at two different times: early and advanced stages of differentiation. We also analyzed differentiation into different cell lines. Results and Conclusions: The effect of sera from patients with NMOSD on precursor cells differs according to the degree of differentiation, and probably affects oligodendrocyte progenitor cells from NG2 cells to a lesser extent than cells from the subventricular zone; however, the resulting oligodendrocytes may be compromised in terms of maturation and possibly limited in their ability to generate myelin. Furthermore, these cells decrease in number with age. It is very unlikely that the use of drugs favoring the migration and differentiation of oligodendrocyte progenitor cells in multiple sclerosis would be effective in the context of neuromyelitis optica, but cell therapy with oligodendrocyte progenitor cells seems to be a potential alternative.

Demyelination-remyelination in the Central Nervous System: Ligand-dependent Participation of the Notch Signaling Pathway

2019 ◽  
Vol 171 (1) ◽  
pp. 172-192 ◽  
Author(s):  
Patricia A Mathieu ◽  
María F Almeira Gubiani ◽  
Débora Rodríguez ◽  
Laura I Gómez Pinto ◽  
María de Luján Calcagno ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Central Nervous System Disease ◽  
Notch Signaling Pathway ◽  
Signaling Activation

Abstract Multiple sclerosis (MS) is an immune-mediated central nervous system disease mostly affecting young people. Multiple sclerosis and other neurodegenerative and white matter disorders involve oligodendrocyte (OL) damage and demyelination. Therefore, elucidating the signaling pathways involved in the remyelination process through the maturation of OL progenitor cells (OPCs) may contribute to the development of new therapeutic approaches. In this context, this paper further characterizes toxic cuprizone (CPZ)-induced demyelination and spontaneous remyelination in rats and investigates the role of ligand-dependent Notch signaling activation along demyelination/remyelination both in vivo and in vitro. Toxic treatment generated an inflammatory response characterized by both microgliosis and astrogliosis. Interestingly, early demyelination revealed an increase in the proportion of Jagged1+/GFAP+ cells, which correlated with an increase in Jagged1 transcript and concomitant Jagged1-driven Notch signaling activation, particularly in NG2+ OPCs, in both the corpus callosum (CC) and subventricular zone (SVZ). The onset of remyelination then exhibited an increase in the proportion of F3/contactin+/NG2+ cells, which correlated with an increase in F3/contactin transcript during ongoing remyelination in the CC. Moreover, neurosphere cultures revealed that neural progenitor cells present in the brain SVZ of CPZ-treated rats recapitulate in vitro the mechanisms underlying the response to toxic injury observed in vivo, compensating for mature OL loss. Altogether, the present results offer strong evidence of cell-type and ligand-specific Notch signaling activation and its time- and area-dependent participation in toxic demyelination and spontaneous remyelination.

Monofocal origin of telencephalic oligodendrocytes in the anterior entopeduncular area of the chick embryo

Development ◽  
2001 ◽  
Vol 128 (10) ◽  
pp. 1757-1769 ◽  
Author(s):  
C. Olivier ◽  
I. Cobos ◽  
E.M. Perez Villegas ◽  
N. Spassky ◽  
B. Zalc ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chick Embryo ◽  
Embryonic Development ◽  
Progenitor Cells ◽  
Oligodendrocyte Progenitor Cells ◽  
Chick Brain ◽  
The Central Nervous System ◽  
The Brain

Oligodendrocytes are the myelin-forming cells in the central nervous system. In the brain, oligodendrocyte precursors arise in multiple restricted foci, distributed along the caudorostral axis of the ventricular neuroepithelium. In chick embryonic hind-, mid- and caudal forebrain, oligodendrocytes have a basoventral origin, while in the rostral fore-brain oligodendrocytes emerge from alar territories (Perez Villegas, E. M., Olivier, C., Spassky, N., Poncet, C., Cochard, P., Zalc, B., Thomas, J. L. and Martinez, S. (1999) Dev. Biol. 216, 98–113). To investigate the respective territories colonized by oligodendrocyte progenitor cells that originate from either the basoventral or alar foci, we have created a series of quail-chick chimeras. Homotopic chimeras demonstrate clearly that, during embryonic development, oligodendrocyte progenitors that emerge from the alar anterior entopeduncular area migrate tangentially to invade the entire telencephalon, whereas those from the basal rhombomeric foci show a restricted rostrocaudal distribution and colonize only their rhombomere of origin. Heterotopic chimeras indicate that differences in the migratory properties of oligodendroglial cells do not depend on their basoventral or alar ventricular origin. Irrespective of their origin (basal or alar), oligodendrocytes migrate only short distances in the hindbrain and long distances in the prosencephalon. Furthermore, we provide evidence that, in the developing chick brain, all telencephalic oligodendrocytes originate from the anterior entopeduncular area and that the prominent role of anterior entopeduncular area in telencephalic oligodendrogenesis is conserved between birds and mammals.

scholarly journals Overcoming the inhibitory microenvironment surrounding oligodendrocyte progenitor cells following experimental demyelination

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Darpan Saraswat ◽  
Hani J. Shayya ◽  
Jessie J. Polanco ◽  
Ajai Tripathi ◽  
R. Ross Welliver ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progenitor Cells ◽  
Demyelinating Disease ◽  
Heparan Sulfate Proteoglycans ◽  
Oligodendrocyte Progenitor Cells ◽  
Subsequent Generation ◽  
Oligodendrocyte Progenitor ◽  
Demyelinating Lesions ◽  
Experimental Demyelination

AbstractChronic demyelination in the human CNS is characterized by an inhibitory microenvironment that impairs recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) leading to failed remyelination and axonal atrophy. By network-based transcriptomics, we identified sulfatase 2 (Sulf2) mRNA in activated human primary OPCs. Sulf2, an extracellular endosulfatase, modulates the signaling microenvironment by editing the pattern of sulfation on heparan sulfate proteoglycans. We found that Sulf2 was increased in demyelinating lesions in multiple sclerosis and was actively secreted by human OPCs. In experimental demyelination, elevated OPC Sulf1/2 expression directly impaired progenitor recruitment and subsequent generation of oligodendrocytes thereby limiting remyelination. Sulf1/2 potentiates the inhibitory microenvironment by promoting BMP and WNT signaling in OPCs. Importantly, pharmacological sulfatase inhibition using PI-88 accelerated oligodendrocyte recruitment and remyelination by blocking OPC-expressed sulfatases. Our findings define an important inhibitory role of Sulf1/2 and highlight the potential for modulation of the heparanome in the treatment of chronic demyelinating disease.

scholarly journals Overcoming the inhibitory microenvironment surrounding oligodendrocyte progenitor cells following demyelination

2020 ◽  
Author(s):  
Darpan Saraswat ◽  
Hani J. Shayya ◽  
Jessie J. Polanco ◽  
Ajai Tripathi ◽  
R. Ross Welliver ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progenitor Cells ◽  
Demyelinating Disease ◽  
Heparan Sulfate Proteoglycans ◽  
Oligodendrocyte Progenitor Cells ◽  
Subsequent Generation ◽  
Oligodendrocyte Progenitor ◽  
Demyelinating Lesions ◽  
Experimental Demyelination

Chronic demyelination in the human CNS is characterized by an inhibitory microenvironment that impairs recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) leading to failed remyelination and axonal atrophy. By network-based transcriptomics, we identified sulfatase 2 (Sulf2) mRNA in activated human primary OPCs. Sulf2, an extracellular endosulfatase, modulates the signaling microenvironment by editing the pattern of sulfation on heparan sulfate proteoglycans. We found that Sulf2 was increased in demyelinating lesions in multiple sclerosis and was actively secreted by human OPCs. In experimental demyelination, elevated OPC Sulf1/2 expression directly impaired progenitor recruitment and subsequent generation of oligodendrocytes thereby limiting remyelination. Sulf1/2 potentiates the inhibitory microenvironment by promoting BMP and WNT signaling in OPCs. Importantly, pharmacological sulfatase inhibition using PI-88 accelerated oligodendrocyte recruitment and remyelination by blocking OPC-expressed sulfatases. Our findings define an important inhibitory role of Sulf1/2 and highlight the potential for modulation of the heparanome in the treatment of chronic demyelinating disease.

scholarly journals New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination

2020 ◽  
Author(s):  
Sarah A Neely ◽  
Jill M Williamson ◽  
Anna Klingseisen ◽  
Lida Zoupi ◽  
Jason J Early ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Cell ◽  
Live Imaging ◽  
Therapeutic Strategies ◽  
Demyelinating Diseases ◽  
Neuronal Cell Bodies ◽  
The Central Nervous System

Regeneration of myelin (remyelination) in the central nervous system (CNS) has long been thought to be principally mediated by newly generated oligodendrocytes, a premise underpinning therapeutic strategies for demyelinating diseases, including multiple sclerosis (MS). Recent studies have indicated that oligodendrocytes that survive demyelination can also contribute to remyelination, including in MS, but it is unclear how remyelination by surviving oligodendrocytes compares to that of newly generated oligodendrocytes. Here we studied oligodendrocytes in MS, and also imaged remyelination in vivo by surviving and new oligodendrocytes using zebrafish. We define a previously unappreciated pathology in MS, myelination of neuronal cell bodies, which is recapitulated during remyelination by surviving oligodendrocytes in zebrafish. Live imaging also revealed that surviving oligodendrocytes make very few new sheaths, but can support sheath growth along axons. In comparison, newly made oligodendrocytes make abundant new sheaths, properly targeted to axons, and exhibit a much greater capacity for regeneration.

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