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Arturo Alvarezbuylla - One of the best experts on this subject based on the ideXlab platform.
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the adult ventricular Subventricular Zone v svz and olfactory bulb ob neurogenesis
Cold Spring Harbor Perspectives in Biology, 2016Co-Authors: Daniel A Lim, Arturo AlvarezbuyllaAbstract:A large population of neural stem/precursor cells (NSCs) persists in the ventricular-Subventricular Zone (V-SVZ) located in the walls of the lateral brain ventricles. V-SVZ NSCs produce large numbers of neuroblasts that migrate a long distance into the olfactory bulb (OB) where they differentiate into local circuit interneurons. Here, we review a broad range of discoveries that have emerged from studies of postnatal V-SVZ neurogenesis: the identification of NSCs as a subpopulation of astroglial cells, the neurogenic lineage, new mechanisms of neuronal migration, and molecular regulators of precursor cell proliferation and migration. It has also become evident that V-SVZ NSCs are regionally heterogeneous, with NSCs located in different regions of the ventricle wall generating distinct OB interneuron subtypes. Insights into the developmental origins and molecular mechanisms that underlie the regional specification of V-SVZ NSCs have also begun to emerge. Other recent studies have revealed new cell-intrinsic molecular mechanisms that enable lifelong neurogenesis in the V-SVZ. Finally, we discuss intriguing differences between the rodent V-SVZ and the corresponding human brain region. The rapidly expanding cellular and molecular knowledge of V-SVZ NSC biology provides key insights into postnatal neural development, the origin of brain tumors, and may inform the development regenerative therapies from cultured and endogenous human neural precursors.
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oligodendrogenesis in the Subventricular Zone and the role of epidermal growth factor
Brain Research Reviews, 2011Co-Authors: Oscar Gonzalezperez, Arturo AlvarezbuyllaAbstract:Demyelinating diseases are characterized by an extensive loss of oligodendrocytes and myelin sheaths from axolemma. These neurological disorders are a common cause of disability in young adults, but so far, there is no effective treatment against them. It has been suggested that neural stem cells (NSCs) may play an important role in brain repair therapies. NSCs in the adult Subventricular Zone (SVZ), also known as Type-B cells, are multipotential cells that can self-renew and give rise to neurons and glia. Recent findings have shown that cells derived from SVZ Type-B cells actively respond to epidermal-growth-factor (EGF) stimulation becoming highly migratory and proliferative. Interestingly, a subpopulation of these EGF-activated cells expresses markers of oligodendrocyte precursor cells (OPCs). When EGF administration is removed, SVZ-derived OPCs differentiate into myelinating and pre-myelinating oligodendrocytes in the white matter tracts of corpus callosum, fimbria fornix and striatum. In the presence of a demyelinating lesion, OPCs derived from EGF-stimulated SVZ progenitors contribute to myelin repair. Given their high migratory potential and their ability to differentiate into myelin-forming cells, SVZ NSCs represent an important endogenous source of OPCs for preserving the oligodendrocyte population in the white matter and for the repair of demyelinating injuries.
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the Subventricular Zone en face wholemount staining and ependymal flow
Journal of Visualized Experiments, 2010Co-Authors: Zaman Mirzadeh, Fiona Doetsch, Hynek Wichterle, Kazunobu Sawamoto, Arturo AlvarezbuyllaAbstract:The walls of the lateral ventricles contain the largest germinal region in the adult mammalian brain. The Subventricular Zone (SVZ) in these walls is an extensively studied model system for understanding the behavior of neural stem cells and the regulation of adult neurogenesis. Traditionally, these studies have relied on classical sectioning techniques for histological analysis. Here we present an alternative approach, the wholemount technique, which provides a comprehensive, en-face view of this germinal region. Compared to sections, wholemounts preserve the complete cytoarchitecture and cellular relationships within the SVZ. This approach has recently revealed that the adult neural stem cells, or type B1 cells, are part of a mixed neuroepithelium with differentiated ependymal cells lining the lateral ventricles. In addition, this approach has been used to study the planar polarization of ependymal cells and the cerebrospinal fluid flow they generate in the ventricle. With recent evidence that adult neural stem cells are a heterogeneous population that is regionally specified, the wholemount approach will likely be an essential tool for understanding the organization and parcellation of this stem cell niche.
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origin of oligodendrocytes in the Subventricular Zone of the adult brain
The Journal of Neuroscience, 2006Co-Authors: Benedicte Menn, David H Rowitch, Jose Manuel Garciaverdugo, Cynthia Yaschine, Oscar Gonzalezperez, Arturo AlvarezbuyllaAbstract:Glial fibrillary acidic protein (GFAP)-positive astrocytes (type B cells) in the Subventricular Zone (SVZ) generate large numbers of new neurons in the adult brain. SVZ stem cells can also generate oligodendrocytes in vitro, but it is not known whether these adult primary progenitors generate oligodendrocytes in vivo. Myelin repair and oligodendrocyte formation in the adult brain is instead associated with glial-restricted progenitors cells, known as oligodendrocyte progenitor cells (OPCs). Here we show that type B cells also generate a small number of nonmyelinating NG2-positive OPCs and mature myelinating oligodendrocytes. Some type B cells and a small subpopulation of actively dividing type C (transit-amplifying) cells expressed oligodendrocyte lineage transcription factor 2 (Olig2), suggesting that oligodendrocyte differentiation in the SVZ begins early in the lineage. Olig2-positive, polysialylated neural cell adhesion molecule-positive, PDGF receptor α-positive, and β-tubulin-negative cells originating in the SVZ migrated into corpus callosum, striatum, and fimbria fornix to differentiate into the NG2-positive nonmyelinating and mature myelinating oligodendrocytes. Furthermore, primary clonal cultures of type B cells gave rise to oligodendrocytes alone or oligodendrocytes and neurons. Importantly, the number of oligodendrocytes derived from type B cells in vivo increased fourfold after a demyelinating lesion in corpus callosum, indicating that SVZ astrocytes participate in myelin repair in the adult brain. Our work identifies SVZ type B cells as progenitors of oligodendrocytes in normal and injured adult brain.
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disruption of eph ephrin signaling affects migration and proliferation in the adult Subventricular Zone
Nature Neuroscience, 2000Co-Authors: Fiona Doetsch, Jose Manuel Garciaverdugo, Nicholas W Gale, George D Yancopoulos, Arturo AlvarezbuyllaAbstract:Disruption of Eph/ephrin signaling affects migration and proliferation in the adult Subventricular Zone
Eduardo Munoz - One of the best experts on this subject based on the ideXlab platform.
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Oral administration of the cannabigerol derivative VCE-003.2 promotes Subventricular Zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration
Translational Neurodegeneration, 2019Co-Authors: José Aguareles, Juan Paraíso-luna, Belén Palomares, Raquel Bajo-grañeras, Carmen Navarrete, Andrea Ruiz-calvo, Daniel García-rincón, Elena García-taboada, Manuel De Guzman, Eduardo MunozAbstract:Background The administration of certain cannabinoids provides neuroprotection in models of neurodegenerative diseases by acting through various cellular and molecular mechanisms. Many cannabinoid actions in the nervous system are mediated by CB_1 receptors, which can elicit psychotropic effects, but other targets devoid of psychotropic activity, including CB_2 and nuclear PPARγ receptors, can also be the target of specific cannabinoids. Methods We investigated the pro-neurogenic potential of the synthetic cannabigerol derivative, VCE-003.2, in striatal neurodegeneration by using adeno-associated viral expression of mutant huntingtin in vivo and mouse embryonic stem cell differentiation in vitro . Results Oral administration of VCE-003.2 protected striatal medium spiny neurons from mutant huntingtin-induced damage, attenuated neuroinflammation and improved motor performance. VCE-003.2 bioavailability was characterized and the potential undesired side effects were evaluated by analyzing hepatotoxicity after chronic treatment. VCE-003.2 promoted Subventricular Zone progenitor mobilization, increased doublecortin-positive migrating neuroblasts towards the injured area, and enhanced effective neurogenesis. Moreover, we demonstrated the proneurogenic activity of VCE-003.2 in embryonic stem cells. VCE-003.2 was able to increase neuroblast formation and striatal-like CTIP2-mediated neurogenesis. Conclusions The cannabigerol derivative VCE-003.2 improves Subventricular Zone-derived neurogenesis in response to mutant huntingtin-induced neurodegeneration, and is neuroprotective by oral administration.
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oral administration of the cannabigerol derivative vce 003 2 promotes Subventricular Zone neurogenesis and protects against mutant huntingtin induced neurodegeneration
Translational neurodegeneration, 2019Co-Authors: José Aguareles, Belén Palomares, Carmen Navarrete, Juan Paraisoluna, Andrea Ruizcalvo, Daniel Garciarincon, Elena Garciataboada, Raquel Bajograneras, Manuel De Guzman, Eduardo MunozAbstract:The administration of certain cannabinoids provides neuroprotection in models of neurodegenerative diseases by acting through various cellular and molecular mechanisms. Many cannabinoid actions in the nervous system are mediated by CB1 receptors, which can elicit psychotropic effects, but other targets devoid of psychotropic activity, including CB2 and nuclear PPARγ receptors, can also be the target of specific cannabinoids. We investigated the pro-neurogenic potential of the synthetic cannabigerol derivative, VCE-003.2, in striatal neurodegeneration by using adeno-associated viral expression of mutant huntingtin in vivo and mouse embryonic stem cell differentiation in vitro. Oral administration of VCE-003.2 protected striatal medium spiny neurons from mutant huntingtin-induced damage, attenuated neuroinflammation and improved motor performance. VCE-003.2 bioavailability was characterized and the potential undesired side effects were evaluated by analyzing hepatotoxicity after chronic treatment. VCE-003.2 promoted Subventricular Zone progenitor mobilization, increased doublecortin-positive migrating neuroblasts towards the injured area, and enhanced effective neurogenesis. Moreover, we demonstrated the proneurogenic activity of VCE-003.2 in embryonic stem cells. VCE-003.2 was able to increase neuroblast formation and striatal-like CTIP2-mediated neurogenesis. The cannabigerol derivative VCE-003.2 improves Subventricular Zone-derived neurogenesis in response to mutant huntingtin-induced neurodegeneration, and is neuroprotective by oral administration.
Fiona Doetsch - One of the best experts on this subject based on the ideXlab platform.
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the Subventricular Zone en face wholemount staining and ependymal flow
Journal of Visualized Experiments, 2010Co-Authors: Zaman Mirzadeh, Fiona Doetsch, Hynek Wichterle, Kazunobu Sawamoto, Arturo AlvarezbuyllaAbstract:The walls of the lateral ventricles contain the largest germinal region in the adult mammalian brain. The Subventricular Zone (SVZ) in these walls is an extensively studied model system for understanding the behavior of neural stem cells and the regulation of adult neurogenesis. Traditionally, these studies have relied on classical sectioning techniques for histological analysis. Here we present an alternative approach, the wholemount technique, which provides a comprehensive, en-face view of this germinal region. Compared to sections, wholemounts preserve the complete cytoarchitecture and cellular relationships within the SVZ. This approach has recently revealed that the adult neural stem cells, or type B1 cells, are part of a mixed neuroepithelium with differentiated ependymal cells lining the lateral ventricles. In addition, this approach has been used to study the planar polarization of ependymal cells and the cerebrospinal fluid flow they generate in the ventricle. With recent evidence that adult neural stem cells are a heterogeneous population that is regionally specified, the wholemount approach will likely be an essential tool for understanding the organization and parcellation of this stem cell niche.
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simultaneous prospective purification of adult Subventricular Zone neural stem cells and their progeny
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Erika Pastrana, Lichun Cheng, Fiona DoetschAbstract:The ability to prospectively isolate adult neural stem cells and their progeny is crucial to study their biology and therapeutic potential. Stem cells in adult mammalian neurogenic niches are a subset of astrocytes. A major limitation in the field has been the inability to distinguish stem cell astrocytes from niche astrocytes. Here, we show that epidermal growth factor receptor (EGFR)-positive Subventricular-Zone (SVZ) astrocytes are activated stem cells that are eliminated by antimitotic treatment. We developed a simple strategy to simultaneously purify cells at different stages of the adult SVZ stem cell lineage by using FACS. This method combines the use of fluorescent EGF ligand, CD24, and GFP expression in GFAP::GFP transgenic mice and allows the simultaneous purification of activated stem cell astrocytes (GFP+EGFR+CD24−), niche astrocytes (GFP+EGFR−CD24−), transit amplifying cells (GFP−EGFR+CD24−), and neuroblasts (GFP−EGFR−CD24low). One in three EGFR+ astrocytes gives rise to neurospheres in vitro, a 20-fold enrichment over unsorted cells. Importantly, these cells constitute the neurosphere-forming population among SVZ astrocytes. This approach will be of great utility for future functional and molecular studies of the SVZ stem cell lineage.
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mir 124 regulates adult neurogenesis in the Subventricular Zone stem cell niche
Nature Neuroscience, 2009Co-Authors: Lichun Cheng, Erika Pastrana, Masoud Tavazoie, Fiona DoetschAbstract:The Subventricular Zone (SVZ) is the largest neurogenic niche in the adult mammalian brain. We found that the brain-enriched microRNA miR-124 is an important regulator of the temporal progression of adult neurogenesis in mice. Knockdown of endogenous miR-124 maintained purified SVZ stem cells as dividing precursors, whereas ectopic expression led to precocious and increased neuron formation. Furthermore, blocking miR-124 function during regeneration led to hyperplasias, followed by a delayed burst of neurogenesis. We identified the SRY-box transcription factor Sox9 as being a physiological target of miR-124 at the transition from the transit amplifying cell to the neuroblast stage. Sox9 overexpression abolished neuronal differentiation, whereas Sox9 knockdown led to increased neuron formation. Thus miR-124-mediated repression of Sox9 is important for progression along the SVZ stem cell lineage to neurons.
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disruption of eph ephrin signaling affects migration and proliferation in the adult Subventricular Zone
Nature Neuroscience, 2000Co-Authors: Fiona Doetsch, Jose Manuel Garciaverdugo, Nicholas W Gale, George D Yancopoulos, Arturo AlvarezbuyllaAbstract:Disruption of Eph/ephrin signaling affects migration and proliferation in the adult Subventricular Zone
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disruption of eph ephrin signaling affects migration and proliferation in the adult Subventricular Zone
Nature Neuroscience, 2000Co-Authors: Fiona Doetsch, Jose Manuel Garciaverdugo, Nicholas W Gale, George D Yancopoulos, Joanne C Conover, Arturo AlvarezbuyllaAbstract:The Subventricular Zone (SVZ) of the lateral ventricles, the largest remaining germinal Zone of the adult mammalian brain, contains an extensive network of neuroblasts migrating rostrally to the olfactory bulb. Little is known about the endogenous proliferation signals for SVZ neural stem cells or guidance cues along the migration pathway. Here we show that the receptor tyrosine kinases EphB1–3 and EphA4 and their transmembrane ligands, ephrins-B2/3, are expressed by cells of the SVZ. Electron microscopy revealed ephrin-B ligands associated with SVZ astrocytes, which function as stem cells in this germinal Zone. A three-day infusion of the ectodomain of either EphB2 or ephrin-B2 into the lateral ventricle disrupted migration of neuroblasts and increased cell proliferation. These results suggest that Eph/ephrin signaling is involved in the migration of neuroblasts in the adult SVZ and in either direct or indirect regulation of cell proliferation.
John A Kessler - One of the best experts on this subject based on the ideXlab platform.
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bone morphogenetic proteins promote astroglial lineage commitment by mammalian Subventricular Zone progenitor cells
Neuron, 1996Co-Authors: Robert E Gross, Peter C. Mabie, Mark F. Mehler, Ziying Zang, Linda Santschi, John A KesslerAbstract:Abstract The epigenetic signals that regulate lineage development in the embryonic mammalian brain are poorly understood. Here we demonstrate that a specific subclass of the transforming growth factor β superfamily, the bone morphogenetic proteins (BMPs), cause the selective, dose-dependent elaboration of the astroglial lineage from murine embryonic Subventricular Zone (SVZ) multipotent progenitor cells. The astroglial inductive effect is characterized by enhanced morphological complexity and expression of glial fibrillary acidic protein, with concurrent suppression of neuronal and oligodendroglial cell fates. SVZ progenitor cells express transcripts for the appropriate BMP-specific type I and II receptor subunits and selective BMP ligands, suggesting the presence of paracrine or autocrine developmental signaling pathways (or both). These observations suggest that the BMPs have a selective role in determining the cell fate of SVZ multipotent progenitor cells or their more developmentally restricted progeny.
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bone morphogenetic proteins promote astroglial lineage commitment by mammalian Subventricular Zone progenitor cells
Neuron, 1996Co-Authors: Robert E Gross, Peter C. Mabie, Mark F. Mehler, Ziying Zang, Linda Santschi, John A KesslerAbstract:The epigenetic signals that regulate lineage development in the embryonic mammalian brain are poorly understood. Here we demonstrate that a specific subclass of the transforming growth factor beta superfamily, the bone morphogenetic proteins (BMPs), cause the selective, dose-dependent elaboration of the astroglial lineage from murine embryonic Subventricular Zone (SVZ) multipotent progenitor cells. The astroglial inductive effect is characterized by enhanced morphological complexity and expression of glial fibrillary acidic protein, with concurrent suppression of neuronal and oligodendroglial cell fates. SVZ progenitor cells express transcripts for the appropriate BMP-specific type I and II receptor subunits and selective BMP ligands, suggesting the presence of paracrine or autocrine developmental signaling pathways (or both). These observations suggest that the BMPs have a selective role in determining the cell fate of SVZ multipotent progenitor cells or their more developmentally restricted progeny.
Michael Chopp - One of the best experts on this subject based on the ideXlab platform.
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Ischemic stroke and neurogenesis in the Subventricular Zone.
Neuropharmacology, 2008Co-Authors: Rui Lan Zhang, Zheng Gang Zhang, Michael ChoppAbstract:The Subventricular Zone (SVZ) of the lateral ventricle contains neural stem and progenitor cells that generate neuroblasts, which migrate to the olfactory bulb where they differentiate into interneurons. Ischemic stroke induces neurogenesis in the SVZ and these cells migrate to the boundary of the ischemic lesion. This article reviews current data on cytokinetics, signaling pathways and vascular niche that are involved in processes of proliferation, differentiation, and migration of neural progenitor cells after stroke.
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stroke induces ependymal cell transformation into radial glia in the Subventricular Zone of the adult rodent brain
Journal of Cerebral Blood Flow and Metabolism, 2007Co-Authors: Rui Lan Zhang, Zheng Gang Zhang, Ying Wang, Yvonne Letourneau, Xueguo Zhang, Sara R Gregg, Lei Wang, Michael ChoppAbstract:Adult ependymal cells are postmitotic and highly differentiated. Radial glial cells are neurogenic precursors. Here, we show that stroke acutely stimulated adult ependymal cell proliferation, and dividing ependymal cells of the lateral ventricle had genotype, phenotype, and morphology of radial glial cells in the rat. The majority of radial glial cells exhibited symmetrical division about the cell cleavage plane, and a radial fiber was maintained throughout each stage of cell mitosis. Increases of radial glial cells parallel expansion of neural progenitors in the Subventricular Zone (SVZ). Furthermore, after stroke radial glial cells derived from the SVZ supported neuron migration. These results indicate that adult ependymal cells divide and transform into radial glial cells after stroke, which could function as neural progenitor cells to generate new neurons and act as scaffolds to support neuroblast migration towards the ischemic boundary region.
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reduction of the cell cycle length by decreasing g1 phase and cell cycle reentry expand neuronal progenitor cells in the Subventricular Zone of adult rat after stroke
Journal of Cerebral Blood Flow and Metabolism, 2006Co-Authors: Rui Lan Zhang, Zheng Gang Zhang, Ying Wang, Mei Lu, James J Yang, Michael ChoppAbstract:A critical determinant of proliferation of progenitor cells is the duration of the cell division cycle. Stroke increases proliferation of progenitor cells in the Subventricular Zone (SVZ). Using cu...
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Proliferation and differentiation of progenitor cells in the cortex and the Subventricular Zone in the adult rat after focal cerebral ischemia.
Neuroscience, 2001Co-Authors: Rui Lan Zhang, Zheng Gang Zhang, Li Zhang, Michael ChoppAbstract:Progenitor cells in the Subventricular Zone of the lateral ventricle and in the dentate gyrus of the hippocampus can proliferate throughout the life of the animal. To examine the proliferation and fate of progenitor cells in the Subventricular Zone and dentate gyrus after focal cerebral ischemia, we measured the temporal and spatial profiles of proliferation of cells and the phenotypic fate of proliferating cells in ischemic brain in a model of embolic middle cerebral artery occlusion in the adult rat. Proliferating cells were labeled by injection of bromodeoxyuridine (BrdU) in a pulse or a cumulative protocol. To determine the temporal profile of proliferating cells, ischemic rats were injected with BrdU every 4 h for 12 h on the day preceding death. Rats were killed 2-14 days after ischemia. We observed significant increases in numbers of proliferating cells in the ipsilateral cortex and Subventricular Zone 2-14 days with a peak at 7 days after ischemia compared with the control group. To maximize labeling of proliferating cells, a single daily injection of BrdU was administered over a 14-day period starting the day after ischemia. Rats were killed either 2 h or 28 days after the last injection of BrdU. A significant increase in numbers of BrdU immunoreactive cells in the Subventricular Zone was coincident with a significant increase in numbers of BrdU immunoreactive cells in the olfactory bulb 14 days after ischemia and numbers of BrdU immunoreactive cells did not significantly increase in the dentate gyrus. However, 28 days after the last labeling, the number of BrdU labeled cells decreased by 90% compared with number at 14 days. Clusters of BrdU labeled cells were present in the cortex distal to the infarction. Numerous cells immunostained for the polysialylated form of the neuronal cell adhesion molecule were detected in the ipsilateral Subventricular Zone. Only 6% of BrdU labeled cells exhibited glial fibrillary acidic protein immunoreactivity in the cortex and subcortex and no BrdU labeled cells expressed neuronal protein markers (neural nuclear protein and microtubule associated protein-2). From these data we suggest that focal cerebral ischemia induces transient and regional specific increases in cell proliferation in the ipsilateral hemisphere and that proliferating progenitor cells may exist in the adult cortex.
