Regulation of L-type Ca++ currents and process morphology in white matter oligodendrocyte precursor cells by golli-myelin proteins

Glia ◽  
2010 ◽  
Vol 58 (11) ◽  
pp. 1292-1303 ◽  
Author(s):  
Daniel Fulton ◽  
Pablo M. Paez ◽  
Robin Fisher ◽  
Vance Handley ◽  
Christopher S. Colwell ◽  
...  
Keyword(s):  
White Matter ◽  
Precursor Cells ◽  
Myelin Proteins ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor ◽  
Ca Currents

Oligodendrocyte precursor cell transplantation promotes angiogenesis and remyelination via Wnt/β-catenin pathway in a mouse model of middle cerebral artery occlusion

2021 ◽  
pp. 0271678X2110653
Author(s):  
Li-Ping Wang ◽  
Jiaji Pan ◽  
Yongfang Li ◽  
Jieli Geng ◽  
Chang Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Cell Transplantation ◽  
Artery Occlusion ◽  
Precursor Cells ◽  
Precursor Cell ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor Cell ◽  
Oligodendrocyte Precursor ◽  
Cerebral Artery Occlusion

White matter injury is a critical pathological characteristic during ischemic stroke. Oligodendrocyte precursor cells participate in white matter repairing and remodeling during ischemic brain injury. Since oligodendrocyte precursor cells could promote Wnt-dependent angiogenesis and migrate along vasculature for the myelination during the development in the central nervous system, we explore whether exogenous oligodendrocyte precursor cell transplantation promotes angiogenesis and remyelination after middle cerebral artery occlusion in mice. Here, oligodendrocyte precursor cell transplantation improved motor and cognitive function, and alleviated brain atrophy. Furthermore, oligodendrocyte precursor cell transplantation promoted functional angiogenesis, and increased myelin basic protein expression after ischemic stroke. The further study suggested that white matter repairing after oligodendrocyte precursor cell transplantation depended on angiogenesis induced by Wnt/β-catenin signal pathway. Our results demonstrated a novel pathway that Wnt7a from oligodendrocyte precursor cells acting on endothelial β-catenin promoted angiogenesis and improved neurobehavioral outcomes, which facilitated white matter repair and remodeling during ischemic stroke.

Inhibition of oligodendrocyte precursor motility by oligodendrocyte processes: implications for transplantation-based approaches to multiple sclerosis

1997 ◽  
Vol 3 (2) ◽  
pp. 162-167 ◽  
Author(s):  
Samantha Jefferson ◽  
Thomas Jacques ◽  
BW Kiernan ◽  
Suzanna Scott-Drew ◽  
Richard Milner ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Time Lapse ◽  
Precursor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor ◽  
Normal White Matter ◽  
Successful Repair

Transplantation of oligodendrocyte precursor cells represents a promising approach to the treatment of the chronic demyelinated lesions of multiple sclerosis. In view of the multi-focal nature of the disease it will be necessary for the transplanted oligodendrocyte precursor cells to migrate through normal white matter between lesions. Work in other systems has shown that differentiated oligodendrocytes within white matter express molecules inhibitory for axon outgrowth. In light of this we have examined the effect of oligodendrocytes on the migration of oligodendrocyte precursors in vitro using time lapse video microscopy. We find that oligodendrocytes induce collapse and loss of motility in oligodendrocyte precursor processes, with this effect being lost as oligodendrocytes undergo programmed cell death. We conclude that the inhibitory factors present on differentiated oligodendrocytes may prevent effective migration between lesion in vivo, and that strategies to overcome this inhibition may be required for successful repair.

scholarly journals Can oligodendrocyte precursor cells be a therapeutic target for mitigating cognitive decline in cerebrovascular disease?

2020 ◽  
Vol 40 (8) ◽  
pp. 1735-1736 ◽  
Author(s):  
Ken Arai
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Memory Deficits ◽  
Vascular Cognitive Impairment ◽  
Precursor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Age Related ◽  
White Matter Development ◽  
Oligodendrocyte Precursor ◽  
Novel Therapeutic

Oligodendrocyte precursor cells (OPCs) give rise to mature myelin-forming oligodendrocytes during white matter development. In adult brains, some populations of OPCs remain to renew oligodendrocyte pools and myelin. Two recent studies highlight the importance of OPCs in white matter homeostasis. Genetic tracing studies suggest that age-related decline in OPCs may contribute to diminished myelin renewal and memory deficits in mouse models. Single cell transcriptomics and imaging may now define specific subsets of OPCs involved in process elaboration, motility and myelination. These advances raise the possibility of pursuing OPCs as novel therapeutic targets for vascular cognitive impairment.

scholarly journals CD200 restrains macrophage attack on oligodendrocyte precursors via toll-like receptor 4 downregulation

2015 ◽  
Vol 36 (4) ◽  
pp. 781-793 ◽  
Author(s):  
Kazuhide Hayakawa ◽  
Loc-Duyen D Pham ◽  
Ji Hae Seo ◽  
Nobukazu Miyamoto ◽  
Takakuni Maki ◽  
...  
Keyword(s):  
White Matter ◽  
Precursor Cells ◽  
Mammalian Brain ◽  
In Vivo Model ◽  
Oligodendrocyte Precursor Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Macrophage Phagocytosis ◽  
Oligodendrocyte Precursor

There are numerous barriers to white matter repair after central nervous system injury and the underlying mechanisms remain to be fully understood. In this study, we propose the hypothesis that inflammatory macrophages in damaged white matter attack oligodendrocyte precursor cells via toll-like receptor 4 signaling thus interfering with this endogenous progenitor recovery mechanism. Primary cell culture experiments demonstrate that peritoneal macrophages can attack and digest oligodendrocyte precursor cells via toll-like receptor 4 signaling, and this phagocytosis of oligodendrocyte precursor cells can be inhibited by using CD200-Fc to downregulate toll-like receptor 4. In an in vivo model of white matter ischemia induced by endothelin-1, treatment with CD200-Fc suppressed toll-like receptor 4 expression in peripherally circulating macrophages, thus restraining macrophage phagocytosis of oligodendrocyte precursor cells and leading to improved myelination. Taken together, these findings suggest that deleterious macrophage effects may occur after white matter ischemia, whereby macrophages attack oligodendrocyte precursor cells and interfere with endogenous recovery responses. Targeting this pathway with CD200 may offer a novel therapeutic approach to amplify endogenous oligodendrocyte precursor cell-mediated repair of white matter damage in mammalian brain.

Inhibition of oligodendrocyte precursor cell differentiation by myelin-associated proteins

2008 ◽  
Vol 24 (3-4) ◽  
pp. E5 ◽  
Author(s):  
Yasir A. Syed ◽  
Alexandra S. Baer ◽  
Gert Lubec ◽  
Harald Hoeger ◽  
Georg Widhalm ◽  
...  
Keyword(s):  
Nervous System ◽  
White Matter ◽  
Neurological Diseases ◽  
Treatment Strategies ◽  
Precursor Cells ◽  
Myelin Proteins ◽  
Regulation Of Expression ◽  
Myelin Membrane ◽  
Associated Proteins ◽  
Oligodendrocyte Precursor

Object Promoting repair of central nervous system (CNS) white matter represents an important approach to easing the course of a number of tragic neurological diseases. For this purpose, strategies are currently being evaluated for transplanting cells capable of generating new oligodendrocytes into areas of demyelination and/or enhancing the potential of endogenous stem/precursor cells to give rise to new oligodendrocytes. Emerging evidence, however, indicates that increasing the presence of cells capable of forming new myelin sheaths is not sufficient to promote repair because of unknown inhibitors that accumulate in lesions as a consequence of myelin degeneration and impair the generation of new oligodendrocytes. The aim of the present study was to characterize the nature of the inhibitory molecules present in myelin. Methods Differentiation of primary rat oligodendrocyte precursor cells (OPCs) in the presence of CNS and peripheral nervous system myelin was assessed by immunocytochemical methods. The authors further characterized the nature of the inhibitors by submitting myelin membrane preparations to biochemical precipitation and digestion. Finally, OPCs were grown on purified Nogo-A, oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein, the most prominent inhibitors of axon regeneration. Results Myelin membrane preparations induced a differentiation block in OPCs that was associated with down-regulation of expression of the transcription factor Nkx2.2. The inhibitory activity in myelin was restricted to the CNS and was predominantly associated with white matter. Furthermore, the results demonstrate that myelin proteins that are distinct from the most prominent inhibitors of axon outgrowth are specific inhibitors of OPC differentiation. Conclusions The inhibitory effect of unknown myelin-associated proteins should be considered in future treatment strategies aimed at enhancing CNS repair.

scholarly journals Sparse interaction between oligodendrocyte precursor cells (NG2+ cells) and nodes of Ranvier in the central nervous system

2017 ◽  
Author(s):  
Lindsay M. De Biase ◽  
Michele L. Pucak ◽  
Shin H. Kang ◽  
Stephanie N. Rodriguez ◽  
Dwight E. Bergles
Keyword(s):  
White Matter ◽  
Action Potentials ◽  
Structural Integrity ◽  
Precursor Cells ◽  
Spatial Proximity ◽  
Oligodendrocyte Precursor Cells ◽  
Nodes Of Ranvier ◽  
Cell Processes ◽  
Oligodendrocyte Precursor ◽  
Nodal Density

ABSTRACTRegeneration of propagating action potentials at nodes of Ranvier allows nerve impulses to be conducted over long distances. Proper nodal function is believed to rely on intimate associations among axons, myelinating oligodendrocytes, and perinodal astrocytes. Studies in the optic nerve, corpus callosum, and spinal cord suggest that NG2+ cells are also key constituents of CNS nodes and that these glia may influence conduction efficacy and formation of axon collaterals. However, the prevalence of NG2+ cell processes at CNS nodes of Ranvier has not been rigorously quantified. Here we used a transgenic mouse expressing membrane-targeted EGFP to visualize the fine processes of NG2+ cells and to quantify the spatial relationship between NG2+ cells and nodes of Ranvier in four distinct CNS white matter tracts. NG2+ cell processes came within close spatial proximity to a small percentage of nodes of Ranvier and approximately half of these spatial interactions were estimated to occur by chance. The majority of NG2+ cell process tips were not found in close proximity to nodes and gray matter NG2+ cells in regions of low nodal density were as morphologically complex as their white matter counterparts, indicating that attraction to nodes does not critically influence the elaboration of NG2+ cell processes. Finally, there was no difference in nodal density between small regions devoid of NG2+ cell processes and those containing numerous NG2+ cells processes, demonstrating that the function of CNS nodes of Ranvier does not require ongoing interaction with NG2+ cells.Significance StatementEffective propagation of action potentials along neuronal axons is dependent upon periodic regeneration of depolarization at nodes of Ranvier. The position, structural integrity, and function of nodes of Ranvier is believed to be regulated, in part, by intimate physical interactions between nearby glial cells and nodes. Clarifying whether oligodendrocyte precursor cells are obligate members of this nodal support system is critical for defining whether these cells contribute to pathologies in which nodal structure is compromised.

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