scholarly journals An Extract of Chinpi, the Dried Peel of the Citrus Fruit Unshiu, Enhances Axonal Remyelination via Promoting the Proliferation of Oligodendrocyte Progenitor Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Hideaki Tokunaga ◽  
Chika Seiwa ◽  
Nozomu Yoshioka ◽  
Kazushige Mizoguchi ◽  
Masahiro Yamamoto ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Progenitor Cells ◽  
Ventricular Zone ◽  
Therapeutic Option ◽  
Herbal Medicines ◽  
Protein Isoforms ◽  
Oligodendrocyte Progenitor Cells ◽  
Rna Helicases ◽  
Oligodendrocyte Progenitor

The aging-induced decrease in axonal myelination/remyelination is due to impaired recruitment and differentiation of oligodendrocyte progenitor cells (OPCs). Our previous studies have shown that a monoclonal antibody to DEAD (Asp-Glu-Ala-Asp) box polypeptide 54 (Ddx54), a member of the DEAD box family of RNA helicases, (1) specifically labels oligodendrocyte lineages, (2) binds to mRNA and protein isoforms of myelin basic proteins (MBP), and (3) regulates migration of OPCs from ventricular zone to corpus callosum in mice. It has also been demonstrated that specific loss of a 21.5 kDa MBP isoform (MBP21.5) reflects demyelination status, and oral administration of an extract of Chinpi, citrus unshiu peel, reversed the aging-induced demyelination. Here, we report that Chinpi treatment induced a specific increase in the MBP21.5, led to the reappearance of Ddx54-expressing cells in ventricular-subventricular zone and corpus callosum of aged mice, and promoted remyelination. Treatment ofin vitroOPC cultures with Chinpi constituents, hesperidin plus narirutin, led to an increase in 5-bromo-2′-deoxyuridine incorporation in Ddx54-expressing OPCs, but not in NG2- or Olig2-expressing cell populations. The present study suggests that Ddx54 plays crucial role in remyelination. Furthermore, Chinpi and Chinpi-containing herbal medicines may be a therapeutic option for the aging-induced demyelination diseases.

scholarly journals Loss of Protein-tyrosine Phosphatase α (PTPα) Increases Proliferation and Delays Maturation of Oligodendrocyte Progenitor Cells

2012 ◽  
Vol 287 (15) ◽  
pp. 12529-12540 ◽  
Author(s):  
Pei-Shan Wang ◽  
Jing Wang ◽  
Yi Zheng ◽  
Catherine J. Pallen
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Oligodendrocyte Progenitor Cells ◽  
Cell Cycle Exit ◽  
Oligodendrocyte Progenitor ◽  
Protein Tyrosine ◽  
Neural Stem Progenitor Cells

Tightly controlled termination of proliferation determines when oligodendrocyte progenitor cells (OPCs) can initiate differentiation and mature into myelin-forming cells. Protein-tyrosine phosphatase α (PTPα) promotes OPC differentiation, but its role in proliferation is unknown. Here we report that loss of PTPα enhanced in vitro proliferation and survival and decreased cell cycle exit and growth factor dependence of OPCs but not neural stem/progenitor cells. PTPα−/− mice have more oligodendrocyte lineage cells in embryonic forebrain and delayed OPC maturation. On the molecular level, PTPα-deficient mouse OPCs and rat CG4 cells have decreased Fyn and increased Ras, Cdc42, Rac1, and Rho activities, and reduced expression of the Cdk inhibitor p27Kip1. Moreover, Fyn was required to suppress Ras and Rho and for p27Kip1 accumulation, and Rho inhibition in PTPα-deficient cells restored expression of p27Kip1. We propose that PTPα-Fyn signaling negatively regulates OPC proliferation by down-regulating Ras and Rho, leading to p27Kip1 accumulation and cell cycle exit. Thus, PTPα acts in OPCs to limit self-renewal and facilitate differentiation.

scholarly journals Identifying the functions of two biomarkers in human oligodendrocyte progenitor cell development

2020 ◽  
Author(s):  
Haipeng Zhou ◽  
Ying He ◽  
Yinxiang Yang ◽  
Zhaoyan Wang ◽  
Qian Wang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Progenitor Cells ◽  
Cell Transplantation ◽  
Cell Population ◽  
Developmental Stages ◽  
Demyelinating Diseases ◽  
Oligodendrocyte Progenitor Cells ◽  
Migration Ability ◽  
Oligodendrocyte Progenitor

AbstractNG2 and A2B5 are important biological markers of human oligodendrocyte progenitor cells. To study their functional differences during the development of human oligodendrocyte progenitor cells to oligodendrocytes, we used cell sorting technology and obtained a large number of sterile, high-purity NG2+/- and A2B5+/- cells with high viability. Further research was then conducted via in vitro cell proliferation and migration assays, single-cell sequencing, mRNA sequencing, and cell transplantation into shiverer mice. The results showed that the migration ability of the cells was inversely proportional to the myelination ability. NG2 may be a marker of early oligodendrocyte progenitor cells and is conducive to cell migration and proliferation, while A2B5 may be a marker of slightly mature oligodendrocyte progenitor cells and is conducive to cell differentiation. Further, cell migration, proliferation, and myelination capacity of the negative cell population were stronger than those of the positive cell population. In summary, these results suggest that oligodendrocyte progenitor cells in the mid-stage may be more suitable for clinical cell transplantation to treat demyelinating diseases.Summary statementThis research found that oligodendrocyte progenitor cells in the middle developmental stages may be more suitable for cell transplantation to treat demyelinating diseases.

Microglial Activation Induces Generation of Oligodendrocyte Progenitor Cells from the Subventricular Zone after Focal Demyelination in the Corpus Callosum

2018 ◽  
Vol 40 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Masae Naruse ◽  
Koji Shibasaki ◽  
Hiroya Shimauchi-Ohtaki ◽  
Yasuki Ishizaki
Keyword(s):  
Corpus Callosum ◽  
Progenitor Cells ◽  
Subventricular Zone ◽  
Microglial Activation ◽  
Neural Progenitor Cells ◽  
Internal Capsule ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Demyelinating Lesions ◽  
Focal Demyelination

Neuroblasts derived from neural stem cells (NSCs) in the subventricular zone (SVZ) migrate along the rostral migratory stream into the olfactory bulb to generate interneurons under normal physiological conditions. When demyelination occurs, NSCs or neural progenitor cells (NPCs) in the SVZ provide newly formed oligodendrocytes to demyelinated lesions. The plasticity of NSC/NPC lineages may tend to oligodendrogenesis under the influence of demyelinated lesions. The mechanisms, however, still remain unknown. This study revealed that focal demyelination in the corpus callosum caused activation of the microglia, not only at the site of demyelination but also in the SVZ, and dramatically increased the generation of oligodendrocyte progenitor cells (OPCs) in the SVZ. Furthermore, the inhibition of microglial activation by minocycline treatment decreased OPC generation in the SVZ, suggesting that microglial activation in the SVZ, induced by the focal demyelination in the corpus callosum, regulates NSC/NPC lineage plasticity in situ. In contrast to the findings regarding demyelination in the corpus callosum, inducing focal demyelination in the internal capsule did not induce either microglial activation or OPC generation in the SVZ. These results suggest that the mechanism of OPC generation in the SVZ after inducing demyelinating lesions could be different across the demyelinated regions.

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.

The regulation of proliferation and differentiation in oligodendrocyte progenitor cells by alphaV integrins

Development ◽  
2000 ◽  
Vol 127 (9) ◽  
pp. 1961-1969 ◽  
Author(s):  
K.L. Blaschuk ◽  
E.E. Frost ◽  
C. ffrench-Constant
Keyword(s):  
Progenitor Cells ◽  
Time Lapse ◽  
Genetically Engineered ◽  
Oligodendrocyte Progenitor Cells ◽  
Integrin Subunit ◽  
Wild Type ◽  
Oligodendrocyte Progenitor ◽  
In The Wild ◽  
Beta3 Integrin

We have previously shown that oligodendrocyte progenitor cells exhibit developmental switching between alphav-associated beta integrin subunits to sequentially express alphavbeta1, alphavbeta3 and alphavbeta5 integrins during differentiation in vitro. To understand the role that alphavveta3 integrin may play in regulating oligodendrocyte progenitor cell behaviour, cells of the rat cell line, CG-4, were genetically engineered to constitutively express alphavbeta3 integrin by transfection with full-length human beta3 integrin subunit cDNA. Time-lapse videomicroscopy showed no effect of beta3 expression on cell migration but revealed enhanced proliferation on vitronectin substrata. Comparison of mitotic indices, as measured by 5-bromo-2′-deoxyuridine incorporation, confirmed that human beta3 integrin-expressing cells exhibited enhanced proliferation, as compared to both vector-only transfected, and wild-type CG-4 cells when switched to differentiation medium from growth medium, but only in cultures grown on vitronectin and not on poly-D-lysine. The effects on proliferation were inhibited by a function-blocking antibody specifically directed against the human beta3 integrin subunit. Human beta3 integrin-expressing cells also exhibited reduced differentiation. This differentiation could be reduced still further by a function-blocking monoclonal antibody against alphavbeta5 integrin, as could differentiation in the wild-type CG-4 cells. Taken together, these results suggest that alphavbeta3 integrin may regulate oligodendroglial cell proliferation and that both downregulation of alphavbeta3 integrin expression and signalling through alphavbeta5 integrin may be critical to continued differentiation in vitro.

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