The Experts below are selected from a list of 6849 Experts worldwide ranked by ideXlab platform
D. Pleasure - One of the best experts on this subject based on the ideXlab platform.
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olig2 plp positive progenitor cells give rise to bergmann glia in the cerebellum
Cell Death and Disease, 2013Co-Authors: Seunghyuk Chung, D. Pleasure, Peng Jiang, Wenbin Deng, Fuzheng GuoAbstract:NG2 (nerve/glial antigen2)-expressing cells represent the largest population of postnatal progenitors in the central nervous system and have been classified as Oligodendroglial progenitor cells, but the fate and function of these cells remain incompletely characterized. Previous studies have focused on characterizing these progenitors in the postnatal and adult subventricular zone and on analyzing the cellular and physiological properties of these cells in white and gray matter regions in the forebrain. In the present study, we examine the types of neural progeny generated by NG2 progenitors in the cerebellum by employing genetic fate mapping techniques using inducible Cre–Lox systems in vivo with two different mouse lines, the Plp-Cre-ERT2/Rosa26-EYFP and Olig2-Cre-ERT2/Rosa26-EYFP double-transgenic mice. Our data indicate that Olig2/Plp-positive NG2 cells display multipotential properties, primarily give rise to Oligodendroglia but, surprisingly, also generate Bergmann glia, which are specialized glial cells in the cerebellum. The NG2+ cells also give rise to astrocytes, but not neurons. In addition, we show that glutamate signaling is involved in distinct NG2+ cell-fate/differentiation pathways and plays a role in the normal development of Bergmann glia. We also show an increase of cerebellar Oligodendroglial lineage cells in response to hypoxic–ischemic injury, but the ability of NG2+ cells to give rise to Bergmann glia and astrocytes remains unchanged. Overall, our study reveals a novel Bergmann glia fate of Olig2/Plp-positive NG2 progenitors, demonstrates the differentiation of these progenitors into various functional glial cell types, and provides significant insights into the fate and function of Olig2/Plp-positive progenitor cells in health and disease.
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astrogliosis in eae spinal cord derivation from radial glia and relationships to Oligodendroglia
Glia, 2007Co-Authors: Peter Bannerman, Ashleigh Hahn, Athena M Soulika, Vittorio Gallo, D. PleasureAbstract:A prominent feature of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) is the accumulation of enlarged, multipolar glial fibrillary acidic protein (GFAP) and brain lipid binding protein (BLBP) immunoreactive astroglia within and at the margins of the inflammatory demyelinative lesions. Whether this astrogliosis is due to both astroglial hyperplasia and hypertrophy or solely to astroglial hypertrophy is controversial. We now report that coincident with the first appearance of inflammation and clinical deficits in mice with myelin oligodendrocyte glycoprotein peptide (MOG peptide)-induced EAE, the radially oriented, bipolar, GFAP, and BLBP positive cells (adult radial glia) present in normal spinal cord white matter undergo mitosis and phenotypic transformation to hypertrophic astroglia. To facilitate visualization of relationships between these hypertrophic astroglia and dying and regenerating Oligodendroglia, we used mice that express enhanced green fluorescent protein (EGFP) in cells of the Oligodendroglial lineage. During the first week after onset of illness, markedly swollen EGFP+ cells without processes were seen within lesions, whereas EGFP+ cells that expressed immunoreactive cleaved caspase-3 were uncommon. These observations support the hypothesis that necrosis contributes to Oligodendroglial loss early in the course of EAE. Later in the illness, EGFP+ cells accumulated amongst hypertrophic astroglia at the margins of the lesions, while the lesions themselves remained depleted of Oligodendroglia, suggesting that migration of Oligodendroglial lineage cells into the lesions was retarded by the intense perilesional gliosis. © 2006 Wiley-Liss, Inc.
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neurotrophin 3 nt 3 diminishes susceptibility of the Oligodendroglial lineage to ampa glutamate receptor mediated excitotoxicity
Journal of Neuroscience Research, 2000Co-Authors: Bryan Kavanaugh, Judith B. Grinspan, Jacqueline S Beesley, Takayuki Itoh, Aki Itoh, D. PleasureAbstract:Prior reports demonstrated that cells of the Oligodendroglial lineage are susceptible to excitotoxic necrosis mediated by α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors (AMPA-GluR), and also showed that these cells express the high affinity neurotrophin receptors, TrkC and TrkA. We now report that: a) Oligodendroglial progenitors (OP) and immature Oligodendroglia are more vulnerable to AMPA-GluR-mediated excitotoxicity than are mature Oligodendroglia; b) TrkC expression falls substantially during differentiation of cultured OP to mature Oligodendroglia, whereas TrkA expression increases markedly; and c) neurotrophin-3, and to a lesser extent, nerve growth factor, protect the Oligodendroglial lineage against AMPA-GluR-mediated excitotoxicity. J. Neurosci. Res. 60:725–732, 2000. © 2000 Wiley-Liss, Inc.
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Myelin gene expression in glia treated with Oligodendroglial trophic factor
Journal of Neurocytology, 1995Co-Authors: B. Q. Krelder, M. M. Burns, M. Morley, I. A. Panek, R. Shaw, Judith B. Grinspan, D. PleasureAbstract:Oligodendroglia synthesize myelin in the CNS. in vitro , Oligodendroglia may be identified by the binding of monoclonal antibodies against galactocerebroside, a myelin-specific galactolipid. Oligodendroglial trophic factor is a protein mitogen for cells of the Oligodendroglial lineage. When Oligodendroglia in cerebral white matter cultures are treated with Oligodendroglial trophic factor, galactocerebroside-positive cells undergo mitosis but fail to express the myelin structural proteins, myelin basic protein and proteolipid protein. Oligodendroglia treated with Oligodendroglial trophic factor, however, do express 2′, 3′-cyclic nucleotide 3′-phosphodiesterase and myelin-associated glycoprotein in a manner similar to Oligodendroglia treated with platelet-derived growth factor. Oligodendroglial trophic factor, therefore, generates a population of somewhat ‘immature’ Oligodendroglia, which are galactocerebroside, myelin-associated glycoprotein and 2′, 3′-cyclic nucleotide 3′ phosphodiesterase positive but myelin basic protein and proteolipid protein negative.
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Partial purification of a novel mitogen for Oligodendroglia
Journal of neuroscience research, 1995Co-Authors: Barbara Kreider, Judith B. Grinspan, M. B. Waterstone, Gregory T. Bramblett, Beau M. Ances, M. Williams, Janet Stern, Virginia M.-y. Lee, D. PleasureAbstract:A protein with a MWapp of 50–70 kDa isolated from the salt extract of crude membranes from neonatal rat brain increases the numbers of Oligodendroglia in mixed glial cultures prepared from neonatal rat cerebral white matter. After partial purification by ion exchange and gel exclusion chromatography, and elution from an SDS-polyacrylamide gel, this protein ( “Oligodendroglial trophic factor,” OTF) elicited half-maximal Oligodendroglial recruitment at a concentration of 5 ng/mL. OTF is a mitogen for Oligodendroglia, and to a lesser extent, for Oligodendroglial progenitor (O2A) cells, but does not stimulate proliferation of astroglia, Schwann cells, or endoneurial fibroblasts. OTF, unlike platelet-derived growth factor (PDGF), is not an Oligodendroglial survival factor. Antibodies against PDGF and basic fibroblast growth factor (bFGF) do not interfere with the accumulation of Oligodendroglia induced by OTF. When OTF is given simultaneously with either PDGF or bFGF, there is an additive increase in the numbers of cells of the Oligodendroglial lineage. © 1995 Wiley-Liss, Inc.
Fengyi Liang - One of the best experts on this subject based on the ideXlab platform.
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Development/Plasticity/Repair Sirtuin 2, a Mammalian Homolog of Yeast Silent Information Regulator-2 Longevity Regulator, Is an Oligodendroglial Protein That Decelerates Cell Differentiation through
2013Co-Authors: Bin Zhang, Eng-ang Ling, Junhong Tang, Qiong Cao, Jing Guo, Fengyi LiangAbstract:Silent information regulator-2 (SIR2) proteins regulate lifespan of diverse organisms, but their distribution and roles in the CNS remain unclear. Here, we show that sirtuin 2 (SIRT2), a mammalian SIR2 homolog, is an Oligodendroglial cytoplasmic protein and localized to the outer and juxtanodal loops in the myelin sheath. Among cytoplasmic proteins of OLN-93 oligodendrocytes, �-tubulin was the main substrate of SIRT2 deacetylase. In cultured primary oligodendrocyte precursors (OLPs), SIRT2 emergence accompanied elevated �-tubulin acetylation and OLP differentiation into the prematurity stage. Small interfering RNA knockdown of SIRT2 increased the �-tubulin acetylation, myelin basic protein expression, and cell arbor complexity of OLPs. SIRT2 overexpression had the opposite effects, and counteracted the cell arborization-promoting effect of overexpressed juxtanodin. SIRT2 mutation concomitantly reduced its deacetylase activity and its impeding effect on OLP arborization. These results demonstrated a counterbalancing role of SIRT2 against a facilitatory effect of tubulin acetylation on Oligodendroglial differentiation. Selective SIRT2 availability to Oligodendroglia may have important implications for myelinogenesis, myelin–axon interaction, and brain aging. Key words: sirtuin 2; tubulin acetylation/deacetylation; oligodendrocyte differentiation; myelination; RNA interference; cytoskeleto
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sirtuin 2 a mammalian homolog of yeast silent information regulator 2 longevity regulator is an Oligodendroglial protein that decelerates cell differentiation through deacetylating α tubulin
The Journal of Neuroscience, 2007Co-Authors: Wenbo Li, Chun Wu, Eng-ang Ling, Yajun Wu, Junhong Tang, Bin Zhang, Fengyi LiangAbstract:Silent information regulator-2 (SIR2) proteins regulate lifespan of diverse organisms, but their distribution and roles in the CNS remain unclear. Here, we show that sirtuin 2 (SIRT2), a mammalian SIR2 homolog, is an Oligodendroglial cytoplasmic protein and localized to the outer and juxtanodal loops in the myelin sheath. Among cytoplasmic proteins of OLN-93 oligodendrocytes, α-tubulin was the main substrate of SIRT2 deacetylase. In cultured primary oligodendrocyte precursors (OLPs), SIRT2 emergence accompanied elevated α-tubulin acetylation and OLP differentiation into the prematurity stage. Small interfering RNA knockdown of SIRT2 increased the α-tubulin acetylation, myelin basic protein expression, and cell arbor complexity of OLPs. SIRT2 overexpression had the opposite effects, and counteracted the cell arborization-promoting effect of overexpressed juxtanodin. SIRT2 mutation concomitantly reduced its deacetylase activity and its impeding effect on OLP arborization. These results demonstrated a counterbalancing role of SIRT2 against a facilitatory effect of tubulin acetylation on Oligodendroglial differentiation. Selective SIRT2 availability to Oligodendroglia may have important implications for myelinogenesis, myelin–axon interaction, and brain aging.
Wenbo Li - One of the best experts on this subject based on the ideXlab platform.
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sirtuin 2 a mammalian homolog of yeast silent information regulator 2 longevity regulator is an Oligodendroglial protein that decelerates cell differentiation through deacetylating α tubulin
The Journal of Neuroscience, 2007Co-Authors: Wenbo Li, Chun Wu, Eng-ang Ling, Yajun Wu, Junhong Tang, Bin Zhang, Fengyi LiangAbstract:Silent information regulator-2 (SIR2) proteins regulate lifespan of diverse organisms, but their distribution and roles in the CNS remain unclear. Here, we show that sirtuin 2 (SIRT2), a mammalian SIR2 homolog, is an Oligodendroglial cytoplasmic protein and localized to the outer and juxtanodal loops in the myelin sheath. Among cytoplasmic proteins of OLN-93 oligodendrocytes, α-tubulin was the main substrate of SIRT2 deacetylase. In cultured primary oligodendrocyte precursors (OLPs), SIRT2 emergence accompanied elevated α-tubulin acetylation and OLP differentiation into the prematurity stage. Small interfering RNA knockdown of SIRT2 increased the α-tubulin acetylation, myelin basic protein expression, and cell arbor complexity of OLPs. SIRT2 overexpression had the opposite effects, and counteracted the cell arborization-promoting effect of overexpressed juxtanodin. SIRT2 mutation concomitantly reduced its deacetylase activity and its impeding effect on OLP arborization. These results demonstrated a counterbalancing role of SIRT2 against a facilitatory effect of tubulin acetylation on Oligodendroglial differentiation. Selective SIRT2 availability to Oligodendroglia may have important implications for myelinogenesis, myelin–axon interaction, and brain aging.
Gregor K. Wenning - One of the best experts on this subject based on the ideXlab platform.
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Limited effects of dysfunctional macroautophagy on the accumulation of extracellularly derived α-synuclein in Oligodendroglia: implications for MSA pathogenesis.
BMC neuroscience, 2018Co-Authors: Lisa Fellner, Gregor K. Wenning, Edith Buchinger, Dominik Brueck, Regina Irschick, Nadia StefanovaAbstract:The progressive neurodegenerative disorder multiple system atrophy (MSA) is characterized by α-synuclein-positive (oligodendro-) glial cytoplasmic inclusions (GCIs). A connection between the abnormal accumulation of α-synuclein in GCIs and disease initiation and progression has been postulated. Mechanisms involved in the formation of GCIs are unclear. Abnormal uptake of α-synuclein from extracellular space, Oligodendroglial overexpression of α-synuclein, and/or dysfunctional protein degradation including macroautophagy have all been discussed. In the current study, we investigated whether dysfunctional macroautophagy aggravates accumulation of extracellular α-synuclein in the Oligodendroglia. We show that Oligodendroglia uptake monomeric and fibrillar extracellular α-synuclein. Blocking macroautophagy through bafilomycin A1 treatment or genetic knockdown of LC3B does not consistently change the level of incorporated α-synuclein in Oligodendroglia exposed to extracellular soluble/monomeric or fibrillar α-synuclein, however leads to higher oxidative stress in combination with fibrillar α-synuclein treatment. Finally, we detected no evidence for GCI-like formation resulting from dysfunctional macroautophagy in Oligodendroglia using confocal microscopy. In summary, isolated dysfunctional macroautophagy is not sufficient to enhance abnormal accumulation of uptaken α-synuclein in vitro, but may lead to increased production of reactive oxygen species in the presence of fibrillar α-synuclein. Multiple complementary pathways are likely to contribute to GCI formation in MSA.
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Limited effects of dysfunctional macroautophagy on the accumulation of extracellularly derived α-synuclein in Oligodendroglia: implications for MSA pathogenesis
BMC, 2018Co-Authors: Lisa Fellner, Gregor K. Wenning, Edith Buchinger, Dominik Brueck, Regina Irschick, Nadia StefanovaAbstract:Abstract Background The progressive neurodegenerative disorder multiple system atrophy (MSA) is characterized by α-synuclein-positive (oligodendro-) glial cytoplasmic inclusions (GCIs). A connection between the abnormal accumulation of α-synuclein in GCIs and disease initiation and progression has been postulated. Mechanisms involved in the formation of GCIs are unclear. Abnormal uptake of α-synuclein from extracellular space, Oligodendroglial overexpression of α-synuclein, and/or dysfunctional protein degradation including macroautophagy have all been discussed. In the current study, we investigated whether dysfunctional macroautophagy aggravates accumulation of extracellular α-synuclein in the Oligodendroglia. Results We show that Oligodendroglia uptake monomeric and fibrillar extracellular α-synuclein. Blocking macroautophagy through bafilomycin A1 treatment or genetic knockdown of LC3B does not consistently change the level of incorporated α-synuclein in Oligodendroglia exposed to extracellular soluble/monomeric or fibrillar α-synuclein, however leads to higher oxidative stress in combination with fibrillar α-synuclein treatment. Finally, we detected no evidence for GCI-like formation resulting from dysfunctional macroautophagy in Oligodendroglia using confocal microscopy. Conclusion In summary, isolated dysfunctional macroautophagy is not sufficient to enhance abnormal accumulation of uptaken α-synuclein in vitro, but may lead to increased production of reactive oxygen species in the presence of fibrillar α-synuclein. Multiple complementary pathways are likely to contribute to GCI formation in MSA
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Multiple system atrophy: pathogenic mechanisms and biomarkers
Journal of Neural Transmission, 2016Co-Authors: Kurt A. Jellinger, Gregor K. WenningAbstract:Multiple system atrophy (MSA) is a unique proteinopathy that differs from other α-synucleinopathies since the pathological process resulting from accumulation of aberrant α-synuclein (αSyn) involves the Oligodendroglia rather than neurons, although both pathologies affect multiple parts of the brain, spinal cord, autonomic and peripheral nervous system. Both the etiology and pathogenesis of MSA are unknown, although animal models have provided insight into the basic molecular changes of this disorder. Accumulation of aberrant αSyn in Oligodendroglial cells and preceded by relocation of p25α protein from myelin to Oligodendroglia results in the formation of insoluble glial cytoplasmic inclusions that cause cell dysfunction and demise. These changes are associated with proteasomal, mitochondrial and lipid transport dysfunction, oxidative stress, reduced trophic transport, neuroinflammation and other noxious factors. Their complex interaction induces dysfunction of the Oligodendroglial-myelin-axon-neuron complex, resulting in the system-specific pattern of neurodegeneration characterizing MSA as a synucleinopathy with oligodendroglio-neuronopathy. Propagation of modified toxic αSyn species from neurons to Oligodendroglia by “prion-like” transfer and its spreading associated with neuronal pathways result in a multi-system involvement. No reliable biomarkers are currently available for the clinical diagnosis and prognosis of MSA. Multidisciplinary research to elucidate the genetic and molecular background of the deleterious cycle of noxious processes, to develop reliable diagnostic biomarkers and to deliver targets for effective treatment of this hitherto incurable disorder is urgently needed.
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The role of α-synuclein in the pathogenesis of multiple system atrophy
Acta Neuropathologica, 2005Co-Authors: Gregor K. Wenning, Kurt A. JellingerAbstract:The discovery of glial cytoplasmic inclusions (GCIs) in 1989 helped to define multiple system atrophy (MSA) as a clinicopathological entity, and drew attention to the prominent role played by these inclusions in the pathogenesis of the disorder. Subsequently, GCIs were shown to be highly positive for α-synuclein, a neuronal protein that is normally absent in Oligodendroglia except during embryonic development. The source of Oligodendroglial α-synuclein aggregation in MSA is unknown. Since genetic overexpression has been excluded, active uptake from dying neurons remains a possibility. The similar topography of Oligodendroglial and neuronal pathology in MSA suggests a fundamental disturbance of the functional unit between Oligodendroglia, axon, and neuron. Transgenic MSA mouse models are now available to determine these aspects of cellular disturbance experimentally.
Bin Zhang - One of the best experts on this subject based on the ideXlab platform.
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Development/Plasticity/Repair Sirtuin 2, a Mammalian Homolog of Yeast Silent Information Regulator-2 Longevity Regulator, Is an Oligodendroglial Protein That Decelerates Cell Differentiation through
2013Co-Authors: Bin Zhang, Eng-ang Ling, Junhong Tang, Qiong Cao, Jing Guo, Fengyi LiangAbstract:Silent information regulator-2 (SIR2) proteins regulate lifespan of diverse organisms, but their distribution and roles in the CNS remain unclear. Here, we show that sirtuin 2 (SIRT2), a mammalian SIR2 homolog, is an Oligodendroglial cytoplasmic protein and localized to the outer and juxtanodal loops in the myelin sheath. Among cytoplasmic proteins of OLN-93 oligodendrocytes, �-tubulin was the main substrate of SIRT2 deacetylase. In cultured primary oligodendrocyte precursors (OLPs), SIRT2 emergence accompanied elevated �-tubulin acetylation and OLP differentiation into the prematurity stage. Small interfering RNA knockdown of SIRT2 increased the �-tubulin acetylation, myelin basic protein expression, and cell arbor complexity of OLPs. SIRT2 overexpression had the opposite effects, and counteracted the cell arborization-promoting effect of overexpressed juxtanodin. SIRT2 mutation concomitantly reduced its deacetylase activity and its impeding effect on OLP arborization. These results demonstrated a counterbalancing role of SIRT2 against a facilitatory effect of tubulin acetylation on Oligodendroglial differentiation. Selective SIRT2 availability to Oligodendroglia may have important implications for myelinogenesis, myelin–axon interaction, and brain aging. Key words: sirtuin 2; tubulin acetylation/deacetylation; oligodendrocyte differentiation; myelination; RNA interference; cytoskeleto
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sirtuin 2 a mammalian homolog of yeast silent information regulator 2 longevity regulator is an Oligodendroglial protein that decelerates cell differentiation through deacetylating α tubulin
The Journal of Neuroscience, 2007Co-Authors: Wenbo Li, Chun Wu, Eng-ang Ling, Yajun Wu, Junhong Tang, Bin Zhang, Fengyi LiangAbstract:Silent information regulator-2 (SIR2) proteins regulate lifespan of diverse organisms, but their distribution and roles in the CNS remain unclear. Here, we show that sirtuin 2 (SIRT2), a mammalian SIR2 homolog, is an Oligodendroglial cytoplasmic protein and localized to the outer and juxtanodal loops in the myelin sheath. Among cytoplasmic proteins of OLN-93 oligodendrocytes, α-tubulin was the main substrate of SIRT2 deacetylase. In cultured primary oligodendrocyte precursors (OLPs), SIRT2 emergence accompanied elevated α-tubulin acetylation and OLP differentiation into the prematurity stage. Small interfering RNA knockdown of SIRT2 increased the α-tubulin acetylation, myelin basic protein expression, and cell arbor complexity of OLPs. SIRT2 overexpression had the opposite effects, and counteracted the cell arborization-promoting effect of overexpressed juxtanodin. SIRT2 mutation concomitantly reduced its deacetylase activity and its impeding effect on OLP arborization. These results demonstrated a counterbalancing role of SIRT2 against a facilitatory effect of tubulin acetylation on Oligodendroglial differentiation. Selective SIRT2 availability to Oligodendroglia may have important implications for myelinogenesis, myelin–axon interaction, and brain aging.
