scholarly journals A Role of Microtubules in Oligodendrocyte Differentiation

2020 ◽  
Vol 21 (3) ◽  
pp. 1062
Author(s):  
Bo Yoon Lee ◽  
Eun-Mi Hur
Keyword(s):  
Neurological Disorders ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Differentiation ◽  
Epothilone B ◽  
Myelin Sheaths ◽  
Simple Protocol ◽  
The Central Nervous System ◽  
Central Nervous System Defects ◽  
Late Stages

Oligodendrocytes are specialized cells that myelinate axons in the central nervous system. Defects in oligodendrocyte function and failure to form or maintain myelin sheaths can cause a number of neurological disorders. Oligodendrocytes are differentiated from oligodendrocyte progenitor cells (OPCs), which extend several processes that contact, elaborate, and eventually wrap axonal segments to form multilayered myelin sheaths. These processes require extensive changes in the cytoarchitecture and must be regulated by reorganization of the cytoskeleton. Here, we established a simple protocol to isolate and differentiate mouse OPCs, and by using this method, we investigated a role of microtubules (MTs) in oligodendrocyte differentiation. Oligodendrocytes developed a complex network of MTs during differentiation, and treatment of differentiating oligodendrocytes with nanomolar concentrations of MT-targeting agents (MTAs) markedly affected oligodendrocyte survival and differentiation. We found that acute exposure to vincristine and nocodazole at early stages of oligodendrocyte differentiation markedly increased MT arborization and enhanced differentiation, whereas taxol and epothilone B treatment produced opposing outcomes. Furthermore, treatment of myelinating co-cultures of oligodendrocytes and neurons with nanomolar concentrations of MTAs at late stages of oligodendrocyte differentiation induced dysmyelination. Together, these results suggest that MTs play an important role in the survival, differentiation, and myelination of oligodendrocytes.

scholarly journals Role of PARP1 in oligodendrocyte differentiation during developmental myelination and remyelination after myelin damage

2021 ◽  
Author(s):  
Yan Wang ◽  
Sheng Zhang ◽  
Bokyung Kim ◽  
Vanessa L. Hull ◽  
Jie Xu ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Rna Binding ◽  
Molecular Level ◽  
Rna Binding Protein ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Differentiation ◽  
Potential Therapeutic Target ◽  
The Central Nervous System ◽  
Cns Myelination

AbstractThe function of poly(ADP-ribosyl) polymerase 1 (PARP1) in myelination and remyelination of the central nervous system (CNS) remain enigmatic. Here we report that PARP1 is an intrinsic driver for oligodendroglial development and myelination. Genetic PARP1 depletion impairs the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and impedes CNS myelination. Mechanistically, PARP1-mediated PARylation activity is not only necessary but also sufficient for OPC differentiation. At the molecular level, we identify the RNA-binding protein Myef2 as a novel PARylated target which we show controls OPC differentiation through PARylation-modulated de-repression of myelin protein expression. Furthermore, PARP1’s enzymatic activity is necessary for oligodendrocyte and myelin regeneration after demyelination. Together, our findings suggest that PARP1-mediated PARylation activity may be a potential therapeutic target for promoting OPC differentiation and remyelination in neurological disorders characterized by arrested OPC differentiation and remyelination failure such as multiple sclerosis.

scholarly journals Intestinal Microbiota as an Alternative Therapeutic Target for Epilepsy

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Jiaying Wu ◽  
Yuyu Zhang ◽  
Hongyu Yang ◽  
Yuefeng Rao ◽  
Jing Miao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Microbiota ◽  
Neurological Disorders ◽  
Digestive System ◽  
Hygiene Hypothesis ◽  
Host Susceptibility ◽  
Immune Disorders ◽  
The Central Nervous System ◽  
Symbiotic Microbiota

Epilepsy is one of the most widespread serious neurological disorders, and an aetiological explanation has not been fully identified. In recent decades, a growing body of evidence has highlighted the influential role of autoimmune mechanisms in the progression of epilepsy. The hygiene hypothesis draws people’s attention to the association between gut microbes and the onset of multiple immune disorders. It is also believed that, in addition to influencing digestive system function, symbiotic microbiota can bidirectionally and reversibly impact the programming of extraintestinal pathogenic immune responses during autoimmunity. Herein, we investigate the concept that the diversity of parasitifer sensitivity to commensal microbes and the specific constitution of the intestinal microbiota might impact host susceptibility to epilepsy through promotion of Th17 cell populations in the central nervous system (CNS).

scholarly journals Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Colony Stimulating Factor ◽  
Loss Of Function ◽  
Axonal Spheroids ◽  
The Central Nervous System ◽  
Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

scholarly journals Features of nervous system damage in antiphospholipid syndrome

2021 ◽  
Vol 15 (4) ◽  
pp. 404-414
Author(s):  
O. N. Voskresenskaya ◽  
V. O. Bitsadze ◽  
J. Kh. Khizroeva ◽  
T. A. Sukontseva ◽  
M. V. Tretyakova ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Antiphospholipid Syndrome ◽  
Neurological Disorders ◽  
Molecular Mimicry ◽  
Transverse Myelitis ◽  
Autoimmune Process ◽  
The Central Nervous System ◽  
Interdisciplinary Interaction

Antiphospholipid syndrome (APS) is an autoimmune process that increases the risk of arterial and venous thrombosis. The mechanism of damage to the central nervous system (CNS) can be not only due to thrombosis, but also antiphospholipid antibodies (APA) circulating in the peripheral blood. The latter can damage the cerebral vascular endothelium, alter the resistance of the blood-brain barrier and penetrate into the central nervous system, exerting a damaging effect on astroglia and neurons, as evidenced by the release of neurospecific proteins into the peripheral bloodstream. The role of APS in developing cerebral ischemia, migraine, epilepsy, chorea, transverse myelitis, multiple sclerosis, cognitive impairment and mental disorders, as well as the peripheral nervous system is described. It should also be noted about a role of APS for emerging neurological disorders in COVID-19, enabled apart from thrombogenesis due to APA via 2 potential mechanisms - molecular mimicry and neoepitope formation. Further study of the APS pathogenesis and interdisciplinary interaction are necessary to develop effective methods for patient management.

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 Notch1 control of oligodendrocyte differentiation in the spinal cord

2002 ◽  
Vol 158 (4) ◽  
pp. 709-718 ◽  
Author(s):  
Stéphane Genoud ◽  
Corinna Lappe-Siefke ◽  
Sandra Goebbels ◽  
Freddy Radtke ◽  
Michel Aguet ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Transgenic Mice ◽  
Oligodendrocyte Differentiation ◽  
Temporal Regulation ◽  
Development And Differentiation ◽  
The Central Nervous System

We have selectively inhibited Notch1 signaling in oligodendrocyte precursors (OPCs) using the Cre/loxP system in transgenic mice to investigate the role of Notch1 in oligodendrocyte (OL) development and differentiation. Early development of OPCs appeared normal in the spinal cord. However, at embryonic day 17.5, premature OL differentiation was observed and ectopic immature OLs were present in the gray matter. At birth, OL apoptosis was strongly increased in Notch1 mutant animals. Premature OL differentiation was also observed in the cerebrum, indicating that Notch1 is required for the correct spatial and temporal regulation of OL differentiation in various regions of the central nervous system. These findings establish a widespread function of Notch1 in the late steps of mammalian OPC development in vivo.

scholarly journals Modeling Neurodevelopmental and Neuropsychiatric Diseases with Astrocytes Derived from Human-Induced Pluripotent Stem Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1692
Author(s):  
Baiyan Ren ◽  
Anna Dunaevsky
Keyword(s):  
Stem Cell ◽  
Neurological Disorders ◽  
Stem Cell Differentiation ◽  
Patient Specific ◽  
Human Astrocytes ◽  
Structural And Functional Properties ◽  
Neuropsychiatric Diseases ◽  
The Central Nervous System ◽  
Induced Pluripotent

Accumulating studies demonstrate the morphological and functional diversity of astrocytes, a subtype of glial cells in the central nervous system. Animal models are instrumental in advancing our understanding of the role of astrocytes in brain development and their contribution to neurological disease; however, substantial interspecies differences exist between rodent and human astrocytes, underscoring the importance of studying human astrocytes. Human pluripotent stem cell differentiation approaches allow the study of patient-specific astrocytes in the etiology of neurological disorders. In this review, we summarize the structural and functional properties of astrocytes, including the unique features of human astrocytes; demonstrate the necessity of the stem cell platform; and discuss how this platform has been applied to the research of neurodevelopmental and neuropsychiatric diseases.

scholarly journals Pericytes for Therapeutic Approaches to Ischemic Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Lu Cao ◽  
Yanbo Zhou ◽  
Mengguang Chen ◽  
Li Li ◽  
Wei Zhang
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ischemic Stroke ◽  
Therapeutic Target ◽  
Neurological Disorders ◽  
Neurovascular Unit ◽  
Therapeutic Approaches ◽  
Multipotent Cells ◽  
The Central Nervous System

Pericytes are perivascular multipotent cells located on capillaries. Although pericytes are discovered in the nineteenth century, recent studies have found that pericytes play an important role in maintaining the blood—brain barrier (BBB) and regulating the neurovascular system. In the neurovascular unit, pericytes perform their functions by coordinating the crosstalk between endothelial, glial, and neuronal cells. Dysfunction of pericytes can lead to a variety of diseases, including stroke and other neurological disorders. Recent studies have suggested that pericytes can serve as a therapeutic target in ischemic stroke. In this review, we first summarize the biology and functions of pericytes in the central nervous system. Then, we focus on the role of dysfunctional pericytes in the pathogenesis of ischemic stroke. Finally, we discuss new therapies for ischemic stroke based on targeting pericytes.

scholarly journals Schwann cell remyelination of the central nervous system: why does it happen and what are the benefits?

Open Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 200352
Author(s):  
Civia Z. Chen ◽  
Björn Neumann ◽  
Sarah Förster ◽  
Robin J. M. Franklin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Current Knowledge ◽  
Oligodendrocyte Progenitor Cells ◽  
Neuronal Function ◽  
Lesion Area ◽  
Myelin Sheaths ◽  
The Central Nervous System ◽  
Review Current ◽  
Surprising Finding

Myelin sheaths, by supporting axonal integrity and allowing rapid saltatory impulse conduction, are of fundamental importance for neuronal function. In response to demyelinating injuries in the central nervous system (CNS), oligodendrocyte progenitor cells (OPCs) migrate to the lesion area, proliferate and differentiate into new oligodendrocytes that make new myelin sheaths. This process is termed remyelination. Under specific conditions, demyelinated axons in the CNS can also be remyelinated by Schwann cells (SCs), the myelinating cell of the peripheral nervous system. OPCs can be a major source of these CNS-resident SCs—a surprising finding given the distinct embryonic origins, and physiological compartmentalization of the peripheral and central nervous system. Although the mechanisms and cues governing OPC-to-SC differentiation remain largely undiscovered, it might nevertheless be an attractive target for promoting endogenous remyelination. This article will (i) review current knowledge on the origins of SCs in the CNS, with a particular focus on OPC to SC differentiation, (ii) discuss the necessary criteria for SC myelination in the CNS and (iii) highlight the potential of using SCs for myelin regeneration in the CNS.

scholarly journals Targeting S100B Protein as a Surrogate Biomarker and its Role in Various Neurological Disorders

2020 ◽  
Vol 19 (2) ◽  
pp. 265-277 ◽  
Author(s):  
Urvashi Langeh ◽  
Shamsher Singh
Keyword(s):  
Neurological Disorders ◽  
Calcium Binding ◽  
Mapk Pathway ◽  
Neuronal Loss ◽  
S100b Protein ◽  
Helix Loop Helix ◽  
Glycation End Products ◽  
The Central Nervous System ◽  
Therapeutic Measures

: Neurological disorders (ND) are the central nervous system (CNS) related complications originated by enhanced oxidative stress, mitochondrial failure and overexpression of proteins like S100B. S100B is a helix-loop-helix protein with the calcium-binding domain associated with various neurological disorders through activation of the MAPK pathway, increased NF-kB expression resulting in cell survival, proliferation and gene up-regulation. S100B protein plays a crucial role in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, Schizophrenia and epilepsy because the high expression of this protein directly targets astrocytes and promotes neuroinflammation. Under stressful conditions, S100B produces toxic effects mediated through receptor for advanced glycation end products (AGE) binding. S100B also mediates neuroprotection, minimizes microgliosis and reduces the expression of tumor necrosis factor (TNF-alpha) but that are concentration- dependent mechanisms. Increased level of S100B is useful for assessing the release of inflammatory markers, nitric oxide and excitotoxicity dependent neuronal loss. The present review summarizes the role of S100B in various neurological disorders and potential therapeutic measures to reduce the prevalence of neurological disorders.

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