Electrical signalling properties of oligodendrocyte precursor cells

Oligodendrocyte precursor cells (OPCs) have become the focus of intense research, not only because they generate myelin-forming oligodendrocytes in the normal CNS, but because they may be suitable for transplantation to treat disorders in which myelin does not form or is damaged, and because they have stem-cell-like properties in that they can generate astrocytes and neurons as well as oligodendrocytes. In this article we review the electrical signalling properties of OPCs, including the synaptic inputs they receive and their use of voltage-gated channels to generate action potentials, and we describe experiments attempting to detect output signalling from OPCs. We discuss controversy over the existence of different classes of OPC with different electrical signalling properties, and speculate on the lineage relationship and myelination potential of these different classes of OPC. Finally, we point out that, since OPCs are the main proliferating cell type in the mature brain, the discovery that they can develop into neurons raises the question of whether more neurons are generated in the mature brain from the classical sites of neurogenesis in the subventricular zone of the lateral ventricle and the hippocampal dentate gyrus or from the far more widely distributed OPCs.

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Lack of astrocytes hinders parenchymal oligodendrocyte precursor cells from reaching a myelinating state in osmolyte-induced demyelination

Acta Neuropathologica Communications ◽

10.1186/s40478-020-01105-2 ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Melanie Lohrberg ◽

Anne Winkler ◽

Jonas Franz ◽

Franziska van der Meer ◽

Torben Ruhwedel ◽

...

Keyword(s):

Subventricular Zone ◽

Central Pontine Myelinolysis ◽

Precursor Cells ◽

Oligodendrocyte Precursor Cells ◽

Pontine Myelinolysis ◽

Oligodendrocyte Precursor ◽

Demyelinating Disorders ◽

Rapid Activation ◽

The Impact ◽

Central Pontine

AbstractDemyelinated lesions in human pons observed after osmotic shifts in serum have been referred to as central pontine myelinolysis (CPM). Astrocytic damage, which is prominent in neuroinflammatory diseases like neuromyelitis optica (NMO) and multiple sclerosis (MS), is considered the primary event during formation of CPM lesions. Although more data on the effects of astrocyte-derived factors on oligodendrocyte precursor cells (OPCs) and remyelination are emerging, still little is known about remyelination of lesions with primary astrocytic loss. In autopsy tissue from patients with CPM as well as in an experimental model, we were able to characterize OPC activation and differentiation. Injections of the thymidine-analogue BrdU traced the maturation of OPCs activated in early astrocyte-depleted lesions. We observed rapid activation of the parenchymal NG2+ OPC reservoir in experimental astrocyte-depleted demyelinated lesions, leading to extensive OPC proliferation. One week after lesion initiation, most parenchyma-derived OPCs expressed breast carcinoma amplified sequence-1 (BCAS1), indicating the transition into a pre-myelinating state. Cells derived from this early parenchymal response often presented a dysfunctional morphology with condensed cytoplasm and few extending processes, and were only sparsely detected among myelin-producing or mature oligodendrocytes. Correspondingly, early stages of human CPM lesions also showed reduced astrocyte numbers and non-myelinating BCAS1+ oligodendrocytes with dysfunctional morphology. In the rat model, neural stem cells (NSCs) located in the subventricular zone (SVZ) were activated while the lesion was already partially repopulated with OPCs, giving rise to nestin+ progenitors that generated oligodendroglial lineage cells in the lesion, which was successively repopulated with astrocytes and remyelinated. These nestin+ stem cell-derived progenitors were absent in human CPM cases, which may have contributed to the inefficient lesion repair. The present study points to the importance of astrocyte-oligodendrocyte interactions for remyelination, highlighting the necessity to further determine the impact of astrocyte dysfunction on remyelination inefficiency in demyelinating disorders including MS.

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

10.1101/185801 ◽

2017 ◽

Cited By ~ 1

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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Faculty Opinions recommendation of Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737829927.793575795 ◽

2020 ◽

Author(s):

Jacqueline Trotter

Keyword(s):

Major Depressive Disorder ◽

Prefrontal Cortex ◽

Depressive Disorder ◽

Precursor Cells ◽

Oligodendrocyte Precursor Cells ◽

Major Depressive ◽

Excitatory Neurons ◽

Single Nucleus ◽

Oligodendrocyte Precursor

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Culture, identification and characterization of rat oligodendrocyte precursor cells in vitro

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2012.00130 ◽

2012 ◽

Vol 32 (2) ◽

pp. 130-135

Author(s):

Mei-lan CHEN ◽

Zhong-jun TANG ◽

Jian MING ◽

Hao WANG ◽

Chun HU ◽

...

Keyword(s):

Precursor Cells ◽

Oligodendrocyte Precursor Cells ◽

Oligodendrocyte Precursor ◽

Culture Identification ◽

Identification And Characterization

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Neuroinflammation in Demyelinating Diseases: Oxidative Stress as a Modulator of Glial Cross-Talk

Current Pharmaceutical Design ◽

10.2174/1381612825666191216125725 ◽

2020 ◽

Vol 25 (45) ◽

pp. 4755-4762 ◽

Cited By ~ 3

Author(s):

Rodrigo Varas ◽

Fernando C. Ortiz

Keyword(s):

Oxidative Stress ◽

Action Potentials ◽

Cell Interaction ◽

Demyelinating Diseases ◽

Signal Molecules ◽

Oligodendrocyte Precursor Cells ◽

Cytokines And Chemokines ◽

Regulatory Aspect ◽

Saltatory Conduction ◽

Oligodendrocyte Precursor

: Myelin is a specialized membrane allowing for saltatory conduction of action potentials in neurons, an essential process to achieve the normal communication across the nervous system. Accordingly, in diseases characterized by the loss of myelin and myelin forming cells -oligodendrocytes in the CNS-, patients show severe neurological disabilities. After a demyelinated insult, microglia, astrocytes and oligodendrocyte precursor cells invade the lesioned area initiating a spontaneous process of myelin repair (i.e. remyelination). A preserved hallmark of this neuroinflammatory scenario is a local increase of oxidative stress, where several cytokines and chemokines are released by glial and other cells. This generates an environment that determines cell interaction resulting in oligodendrocyte maturity and the ability to synthesize new myelin. Herein we review the main features of the regulatory aspect of these molecules based on recent findings and propose new putative signal molecules involved in the remyelination process, focused in the etiology of Multiple Sclerosis, one of the main demyelinating diseases causing disabilities in the population.

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