scholarly journals Tapping into the glial reservoir: cells committed to remaining uncommitted

2010 ◽  
Vol 188 (3) ◽  
pp. 305-312 ◽  
Author(s):  
S.Y. Christin Chong ◽  
Jonah R. Chan
Keyword(s):  
Central Nervous System ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Precursor Cell ◽  
Oligodendrocyte Precursor Cell ◽  
Spatiotemporal Regulation ◽  
Proliferation And Differentiation ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
Widespread Interest

The development and maturation of the oligodendrocyte requires a series of highly orchestrated events that coordinate the proliferation and differentiation of the oligodendrocyte precursor cell (OPC) as well as the spatiotemporal regulation of myelination. In recent years, widespread interest has been devoted to the therapeutic potential of adult OPCs scattered throughout the central nervous system (CNS). In this review, we highlight molecular mechanisms controlling OPC differentiation during development and the implication of these mechanisms on adult OPCs for remyelination. Cell-autonomous regulators of differentiation and the heterogeneous microenvironment of the developing and the adult CNS may provide coordinated inhibitory cues that ultimately maintain a reservoir of uncommitted glia.

Understanding the Molecular Basis of Cell Migration; Implications for Clinical Therapy in Multiple Sclerosis

1997 ◽  
Vol 92 (2) ◽  
pp. 113-122 ◽  
Author(s):  
Richard Milner
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Cell Migration ◽  
Molecular Mechanisms ◽  
Autoimmune Response ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
Oligodendrocyte Precursors

1. Multiple sclerosis is characterized by areas of demyelination spread throughout the central nervous system, in which the myelin sheaths surrounding axons are destroyed. While therapies aimed at suppressing the autoimmune response, such as β-interferon, may prevent further damage, they cannot repair or replace the lost myelin. To this end, an additional therapy has been proposed, which involves transplanting cells of the oligodendrocyte lineage into the central nervous system. 2. The cell of interest for transplantation is the oligodendrocyte precursor because, unlike the differentiated cell, it is an intrinsically migratory and proliferative cell. In order to optimize the transplant strategy we have investigated the molecular mechanisms that control migration in vitro, so that these mechanisms might be upregulated to maximize cell migration in vivo. We have focused on the integrin family of cell adhesion molecules, known to play a fundamental role in the regulation of migration in other cell types. 3. These studies show that oligodendrocytes express a limited repertoire of integrins consisting of α6β1 and three different αv integrins. α6β1 is expressed throughout development but αv integrins show developmental regulation; differentiation is accompanied by loss of αvβ1 and upregulation of αvβ5. 4. Function-blocking studies show that oligodendrocyte precursor migration in vitro is mediated primarily by the developmentally regulated αvβ1 integrin, but not α6β1 or αvβ3. Taken together with previous evidence that cell migration can be regulated by altering integrin expression, this work suggests that modifying expression levels of αvβ1 on oligodendrocyte precursors may increase the migratory capacity of these cells. If so, this would support a future therapeutic strategy aimed at transplanting genetically modified oligodendrocyte precursors to repair widespread demyelinated lesions.

scholarly journals Premyelinating Oligodendrocytes: Mechanisms Underlying Cell Survival and Integration

2021 ◽  
Vol 9 ◽  
Author(s):  
Ethan G. Hughes ◽  
Michael E. Stockton
Keyword(s):  
Brain Function ◽  
Demyelinating Disease ◽  
Precursor Cell ◽  
Oligodendrocyte Precursor Cell ◽  
Mature Oligodendrocyte ◽  
Myelin Sheaths ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
Apoptotic Pathways ◽  
New Treatments

In the central nervous system, oligodendrocytes produce myelin sheaths that enwrap neuronal axons to provide trophic support and increase conduction velocity. New oligodendrocytes are produced throughout life through a process referred to as oligodendrogenesis. Oligodendrogenesis consists of three canonical stages: the oligodendrocyte precursor cell (OPC), the premyelinating oligodendrocyte (preOL), and the mature oligodendrocyte (OL). However, the generation of oligodendrocytes is inherently an inefficient process. Following precursor differentiation, a majority of premyelinating oligodendrocytes are lost, likely due to apoptosis. If premyelinating oligodendrocytes progress through this survival checkpoint, they generate new myelinating oligodendrocytes in a process we have termed integration. In this review, we will explore the intrinsic and extrinsic signaling pathways that influence preOL survival and integration by examining the intrinsic apoptotic pathways, metabolic demands, and the interactions between neurons, astrocytes, microglia, and premyelinating oligodendrocytes. Additionally, we will discuss similarities between the maturation of newly generated neurons and premyelinating oligodendrocytes. Finally, we will consider how increasing survival and integration of preOLs has the potential to increase remyelination in multiple sclerosis. Deepening our understanding of premyelinating oligodendrocyte biology may open the door for new treatments for demyelinating disease and will help paint a clearer picture of how new oligodendrocytes are produced throughout life to facilitate brain function.

RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neuropsychiatric Disorders ◽  
Extensive Literature ◽  
Ang Ii ◽  
Mas Receptor ◽  
The Central Nervous System ◽  
The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

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