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Article ; Online: Adult neural stem cells in the mammalian central nervous system.

Ma, Dengke K / Bonaguidi, Michael A / Ming, Guo-Li / Song, Hongjun

2009 Volume 19, Issue 6, Page(s) 672–682

Abstract: ... brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, including ... in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables ... Neural stem cells (NSCs) are present not only during the embryonic development but also ...

Abstract	Neural stem cells (NSCs) are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, including topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.
MeSH term(s)	Adult Stem Cells/physiology ; Brain/pathology ; Brain/physiology ; Cell Differentiation ; Central Nervous System/cytology ; Humans ; Neurogenesis ; Neuronal Plasticity ; Neurons/physiology
Language	English
Publishing date	2009-05-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1319303-x
ISSN	1748-7838 ; 1001-0602
ISSN (online)	1748-7838
ISSN	1001-0602
DOI	10.1038/cr.2009.56
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Article: Identification of a neural stem cell in the adult mammalian central nervous system.

Johansson, C B / Momma, S / Clarke, D L / Risling, M / Lendahl, U / Frisén, J

Cell

1999 Volume 96, Issue 1, Page(s) 25–34

Abstract: ... neural stem cells and identify a novel process in the response to central nervous system injury. ... central nervous system. These neurons are derived from multipotent stem cells whose identity has been enigmatic ... In this work, we present evidence that ependymal cells are neural stem cells. Ependymal cells give rise ...

Abstract	New neurons are continuously added in specific regions of the adult mammalian central nervous system. These neurons are derived from multipotent stem cells whose identity has been enigmatic. In this work, we present evidence that ependymal cells are neural stem cells. Ependymal cells give rise to a rapidly proliferating cell type that generates neurons that migrate to the olfactory bulb. In response to spinal cord injury, ependymal cell proliferation increases dramatically to generate migratory cells that differentiate to astrocytes and participate in scar formation. These data demonstrate that ependymal cells are neural stem cells and identify a novel process in the response to central nervous system injury.
MeSH term(s)	Animals ; Astrocytes/cytology ; Astrocytes/physiology ; Biomarkers ; Cell Division ; Central Nervous System/cytology ; Heart Ventricles/cytology ; Mammals ; Membrane Proteins/analysis ; Mice ; Neurons/cytology ; Neurons/physiology ; Olfactory Bulb/cytology ; Rats ; Receptor, Notch1 ; Receptors, Cell Surface ; Spinal Cord/cytology ; Spinal Cord Injuries/physiopathology ; Stem Cells/cytology ; Stem Cells/physiology ; Transcription Factors
Chemical Substances	Biomarkers ; Membrane Proteins ; Notch1 protein, mouse ; Notch1 protein, rat ; Receptor, Notch1 ; Receptors, Cell Surface ; Transcription Factors
Language	English
Publishing date	1999-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/s0092-8674(00)80956-3
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Article ; Online: AAV ablates neurogenesis in the adult murine hippocampus.

Johnston, Stephen / Parylak, Sarah L / Kim, Stacy / Mac, Nolan / Lim, Christina / Gallina, Iryna / Bloyd, Cooper / Newberry, Alexander / Saavedra, Christian D / Novak, Ondrej / Gonçalves, J Tiago / Gage, Fred H / Shtrahman, Matthew

eLife

2021 Volume 10

Abstract: ... cells within 18 hr post-injection and no evidence of recovery of adult neurogenesis at 3 months post ... in the DG and as a gene therapy for diseases of the central nervous system should be carefully evaluated. ... progenitor cells (NPCs) and immature dentate granule cells (DGCs) within the adult murine hippocampus are ...

Abstract	Recombinant adeno-associated virus (rAAV) has been widely used as a viral vector across mammalian biology and has been shown to be safe and effective in human gene therapy. We demonstrate that neural progenitor cells (NPCs) and immature dentate granule cells (DGCs) within the adult murine hippocampus are particularly sensitive to rAAV-induced cell death. Cell loss is dose dependent and nearly complete at experimentally relevant viral titers. rAAV-induced cell death is rapid and persistent, with loss of BrdU-labeled cells within 18 hr post-injection and no evidence of recovery of adult neurogenesis at 3 months post-injection. The remaining mature DGCs appear hyperactive 4 weeks post-injection based on immediate early gene expression, consistent with previous studies investigating the effects of attenuating adult neurogenesis. In vitro application of AAV or electroporation of AAV2 inverted terminal repeats (ITRs) is sufficient to induce cell death. Efficient transduction of the dentategyrus (DG)- without ablating adult neurogenesis- can be achieved by injection of rAAV2-retro serotyped virus into CA3. rAAV2-retro results in efficient retrograde labeling of mature DGCs and permits in vivo two-photon calcium imaging of dentate activity while leaving adult neurogenesis intact. These findings expand on recent reports implicating rAAV-linked toxicity in stem cells and other cell types and suggest that future work using rAAV as an experimental tool in the DG and as a gene therapy for diseases of the central nervous system should be carefully evaluated.
MeSH term(s)	Adult ; Animals ; Cell Death ; Cell Proliferation ; Central Nervous System ; Dependovirus ; Genetic Therapy ; Genetic Vectors ; Hippocampus/cytology ; Hippocampus/physiology ; Humans ; Inflammation ; Male ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells/physiology ; Neurogenesis/physiology ; Neurons
Language	English
Publishing date	2021-07-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.59291
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Article ; Online: Adult neurogenesis in the mammalian dentate gyrus.

Abbott, Louise C / Nigussie, Fikru

Anatomia, histologia, embryologia

2019 Volume 49, Issue 1, Page(s) 3–16

Abstract: ... central nervous system. Evidence now indicates that new neurons do form in the adult mammalian brain. Two regions ... early postnatal development, neural stem cells (NSCs) give rise to differentiated neurons. NSCs persist ... the death of some newly formed cells and final integration of surviving cells into neural ...

Abstract	Earlier observations in neuroscience suggested that no new neurons form in the mature central nervous system. Evidence now indicates that new neurons do form in the adult mammalian brain. Two regions of the mature mammalian brain generate new neurons: (a) the border of the lateral ventricles of the brain (subventricular zone) and (b) the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. This review focuses only on new neuron formation in the dentate gyrus of the hippocampus. During normal prenatal and early postnatal development, neural stem cells (NSCs) give rise to differentiated neurons. NSCs persist in the dentate gyrus SGZ, undergoing cell division, with some daughter cells differentiating into functional neurons that participate in learning and memory and general cognition through integration into pre-existing neural networks. Axons, which emanate from neurons in the entorhinal cortex, synapse with dendrites of the granule cells (small neurons) of the dentate gyrus. Axons from granule cells synapse with pyramidal cells in the hippocampal CA3 region, which send axons to synapse with CA1 hippocampal pyramidal cells that send their axons out of the hippocampus proper. Adult neurogenesis includes proliferation, differentiation, migration, the death of some newly formed cells and final integration of surviving cells into neural networks. We summarise these processes in adult mammalian hippocampal neurogenesis and discuss the roles of major signalling molecules that influence neurogenesis, including neurotransmitters and some hormones. The recent controversy raised concerning whether or not adult neurogenesis occurs in humans also is discussed.
MeSH term(s)	Adult ; Animals ; Astrocytes/metabolism ; Cell Differentiation ; Cell Proliferation ; Cellular Microenvironment/physiology ; Dentate Gyrus/cytology ; Epigenomics ; Hippocampus/cytology ; Hormones ; Humans ; Lateral Ventricles/cytology ; Mammals/anatomy & histology ; Memory ; Neural Stem Cells/cytology ; Neurogenesis/physiology ; Neurons/cytology ; Signal Transduction
Chemical Substances	Hormones
Language	English
Publishing date	2019-09-30
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	537922-2
ISSN	1439-0264 ; 0340-2096 ; 0044-4294
ISSN (online)	1439-0264
ISSN	0340-2096 ; 0044-4294
DOI	10.1111/ahe.12496
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Article: Adult neurogenesis in the mammalian dentate gyrus

Abbott, Louise C / Nigussie, Fikru

Anatomia, histologia, embryologia. 2020 Jan., v. 49, no. 1

2020

Abstract	Earlier observations in neuroscience suggested that no new neurons form in the mature central nervous system. Evidence now indicates that new neurons do form in the adult mammalian brain. Two regions of the mature mammalian brain generate new neurons: (a) the border of the lateral ventricles of the brain (subventricular zone) and (b) the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. This review focuses only on new neuron formation in the dentate gyrus of the hippocampus. During normal prenatal and early postnatal development, neural stem cells (NSCs) give rise to differentiated neurons. NSCs persist in the dentate gyrus SGZ, undergoing cell division, with some daughter cells differentiating into functional neurons that participate in learning and memory and general cognition through integration into pre‐existing neural networks. Axons, which emanate from neurons in the entorhinal cortex, synapse with dendrites of the granule cells (small neurons) of the dentate gyrus. Axons from granule cells synapse with pyramidal cells in the hippocampal CA3 region, which send axons to synapse with CA1 hippocampal pyramidal cells that send their axons out of the hippocampus proper. Adult neurogenesis includes proliferation, differentiation, migration, the death of some newly formed cells and final integration of surviving cells into neural networks. We summarise these processes in adult mammalian hippocampal neurogenesis and discuss the roles of major signalling molecules that influence neurogenesis, including neurotransmitters and some hormones. The recent controversy raised concerning whether or not adult neurogenesis occurs in humans also is discussed.
Keywords	adults ; axons ; cell death ; cell division ; cognition ; cortex ; dendrites ; hippocampus ; hormones ; humans ; memory ; neural stem cells ; neurogenesis ; neurophysiology ; neurotransmitters ; postnatal development ; synapse
Language	English
Dates of publication	2020-01
Size	p. 3-16.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	537922-2
ISSN	1439-0264 ; 0340-2096 ; 0044-4294
ISSN (online)	1439-0264
ISSN	0340-2096 ; 0044-4294
DOI	10.1111/ahe.12496
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Article ; Online: AAV ablates neurogenesis in the adult murine hippocampus

Stephen Johnston / Sarah L Parylak / Stacy Kim / Nolan Mac / Christina Lim / Iryna Gallina / Cooper Bloyd / Alexander Newberry / Christian D Saavedra / Ondrej Novak / J Tiago Gonçalves / Fred H Gage / Matthew Shtrahman

eLife, Vol

2021 Volume 10

Abstract	Recombinant adeno-associated virus (rAAV) has been widely used as a viral vector across mammalian biology and has been shown to be safe and effective in human gene therapy. We demonstrate that neural progenitor cells (NPCs) and immature dentate granule cells (DGCs) within the adult murine hippocampus are particularly sensitive to rAAV-induced cell death. Cell loss is dose dependent and nearly complete at experimentally relevant viral titers. rAAV-induced cell death is rapid and persistent, with loss of BrdU-labeled cells within 18 hr post-injection and no evidence of recovery of adult neurogenesis at 3 months post-injection. The remaining mature DGCs appear hyperactive 4 weeks post-injection based on immediate early gene expression, consistent with previous studies investigating the effects of attenuating adult neurogenesis. In vitro application of AAV or electroporation of AAV2 inverted terminal repeats (ITRs) is sufficient to induce cell death. Efficient transduction of the dentategyrus (DG)– without ablating adult neurogenesis– can be achieved by injection of rAAV2-retro serotyped virus into CA3. rAAV2-retro results in efficient retrograde labeling of mature DGCs and permits in vivo two-photon calcium imaging of dentate activity while leaving adult neurogenesis intact. These findings expand on recent reports implicating rAAV-linked toxicity in stem cells and other cell types and suggest that future work using rAAV as an experimental tool in the DG and as a gene therapy for diseases of the central nervous system should be carefully evaluated.
Keywords	hippocampus ; dentate gyrus ; adult neurogenesis ; adeno-associated virus (AAV) ; neural progenitor cell ; gene therapy ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	610 ; 572
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: P2X7 receptor signaling during adult hippocampal neurogenesis.

Leeson, Hannah C / Chan-Ling, Tailoi / Lovelace, Michael D / Brownlie, Jeremy C / Gu, Ben J / Weible, Michael W

Neural regeneration research

2019 Volume 14, Issue 10, Page(s) 1684–1694

Abstract: ... regulate the physiology of stem and progenitor cells in the adult hippocampus is an important step ... physiology of the hippocampus, and neural stem and progenitor cells. ... P2X7 receptors in the central nervous system has attracted much interest and the regulatory role ...

Abstract	Neurogenesis is a persistent and essential feature of the adult mammalian hippocampus. Granular neurons generated from resident pools of stem or progenitor cells provide a mechanism for the formation and consolidation of new memories. Regulation of hippocampal neurogenesis is complex and multifaceted, and numerous signaling pathways converge to modulate cell proliferation, apoptosis, and clearance of cellular debris, as well as synaptic integration of newborn immature neurons. The expression of functional P2X7 receptors in the central nervous system has attracted much interest and the regulatory role of this purinergic receptor during adult neurogenesis has only recently begun to be explored. P2X7 receptors are exceptionally versatile: in their canonical role they act as adenosine triphosphate-gated calcium channels and facilitate calcium-signaling cascades exerting control over the cell via calcium-encoded sensory proteins and transcription factor activation. P2X7 also mediates transmembrane pore formation to regulate cytokine release and facilitate extracellular communication, and when persistently stimulated by high extracellular adenosine triphosphate levels large P2X7 pores form, which induce apoptotic cell death through cytosolic ion dysregulation. Lastly, as a scavenger receptor P2X7 directly facilitates phagocytosis of the cellular debris that arises during neurogenesis, as well as during some disease states. Understanding how P2X7 receptors regulate the physiology of stem and progenitor cells in the adult hippocampus is an important step towards developing useful therapeutic models for regenerative medicine. This review considers the relevant aspects of adult hippocampal neurogenesis and explores how P2X7 receptor activity may influence the molecular physiology of the hippocampus, and neural stem and progenitor cells.
Language	English
Publishing date	2019-06-05
Publishing country	India
Document type	Journal Article
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.257510
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Article ; Online: Isolation of Neural Stem Cells from Whole Brain Tissues of Adult Mice.

Deshpande, Krutika / Saatian, Behnaz / Martirosian, Vahan / Lin, Michelle / Julian, Alex / Neman, Josh

Current protocols in stem cell biology

2019 Volume 49, Issue 1, Page(s) e80

Abstract: A population of neural stem cells exists in the adult mammalian central nervous system ... differentiation of neural stem cells both in vitro and in vivo. Successful stimulation and production ... passage, and maintain the adult neurospheres, and how to differentiate the pure neurospheres ...

Abstract	A population of neural stem cells exists in the adult mammalian central nervous system. Purification and characterization of neurospheres provide valuable tools to study the regulation and differentiation of neural stem cells both in vitro and in vivo. Successful stimulation and production of neurospheres can ultimately be used for therapeutic purposes. The currently available methods are limited by their poor yield and the large number of animals required to compensate for that. Here, we describe a procedure to purify neurospheres from adult mouse whole brain. We provide detailed steps on how to propagate, passage, and maintain the adult neurospheres, and how to differentiate the pure neurospheres into the lineage of interest. Using this method, neurospheres can be easily derived from adult mouse whole brain. The derived adult neurospheres maintain their homogenous undifferentiated status while retaining their differentiation potential. This new protocol facilitates adult neurospheres isolation, purification, maintenance, and differentiation. © 2019 by John Wiley & Sons, Inc.
MeSH term(s)	Animals ; Brain/cytology ; Cell Culture Techniques/methods ; Cell Separation/methods ; Cells, Cultured ; Mice ; Neural Stem Cells/cytology ; Neurons/cytology
Language	English
Publishing date	2019-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1938-8969
ISSN (online)	1938-8969
DOI	10.1002/cpsc.80
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Article ; Online: Adult astrocytes from reptiles are resistant to proinflammatory activation via sustaining Vav1 expression.

Du, Nan / Li, Hui / Sun, Chunshuai / He, Bingqiang / Yang, Ting / Song, Honghua / Wang, Yingjie / Wang, Yongjun

The Journal of biological chemistry

2021 Volume 296, Page(s) 100527

Abstract: ... or mechanical injury, thereby affecting functional outcomes of the central nervous system (CNS ... mediated inflammation in the severed cords remains unclear. Here, we compared neural stem cell markers among gAS ... Adult mammalian astrocytes are sensitive to inflammatory stimuli in the context of neuropathology ...

Abstract	Adult mammalian astrocytes are sensitive to inflammatory stimuli in the context of neuropathology or mechanical injury, thereby affecting functional outcomes of the central nervous system (CNS). In contrast, glial cells residing in the spinal cord of regenerative vertebrates exhibit a weak astroglial reaction similar to those of mammals in embryonic stages. Macrophage migration inhibitory factor (MIF) participates in multiple neurological disorders by activation of glial and immune cells. However, the mechanism of astrocytes from regenerative species, such as gecko astrocytes (gAS), in resistance to MIF-mediated inflammation in the severed cords remains unclear. Here, we compared neural stem cell markers among gAS, as well as adult (rAS) and embryonic (eAS) rat astrocytes. We observed that gAS retained an immature phenotype resembling rat eAS. Proinflammatory activation of gAS with gecko (gMIF) or rat (rMIF) recombinant protein was unable to induce the production of inflammatory cytokines, despite its interaction with membrane CD74 receptor. Using cross-species screening of inflammation-related mediators from models of gMIF- and rMIF-induced gAS and rAS, we identified Vav1 as a key regulator in suppressing the inflammatory activation of gAS. The gAS with Vav1 deficiency displayed significantly restored sensitivity to inflammatory stimuli. Meanwhile, gMIF acts to promote the migration of gAS through regulation of CXCL8 following cord lesion. Taken together, our results suggest that Vav1 contributes to the regulation of astrocyte-mediated inflammation, which might be beneficial for the therapeutic development of neurological diseases.
MeSH term(s)	Animals ; Astrocytes/cytology ; Astrocytes/immunology ; Astrocytes/metabolism ; Biomarkers/metabolism ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Inflammation/immunology ; Inflammation/metabolism ; Inflammation/pathology ; Inflammation Mediators/metabolism ; Macrophage Migration-Inhibitory Factors/genetics ; Macrophage Migration-Inhibitory Factors/metabolism ; Proto-Oncogene Proteins c-vav/genetics ; Proto-Oncogene Proteins c-vav/metabolism ; Rats ; Reptiles ; Spinal Cord/cytology ; Spinal Cord/immunology ; Spinal Cord/metabolism
Chemical Substances	Biomarkers ; Inflammation Mediators ; Macrophage Migration-Inhibitory Factors ; Proto-Oncogene Proteins c-vav
Language	English
Publishing date	2021-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2021.100527
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Article ; Online: Treating Brain Disorders by Targeting Adult Neural Stem Cells.

Bao, Hechen / Song, Juan

Trends in molecular medicine

2018 Volume 24, Issue 12, Page(s) 991–1006

Abstract: ... our understanding of the key properties and potential functions of adult neural stem cells. We further discuss ... from neural stem cells, occurs throughout life in the hippocampus of the mammalian brain and highlights the plastic ... nature of the mature central nervous system. Substantial evidence suggests that new neurons participate ...

Abstract	Adult neurogenesis, a developmental process of generating functionally integrated neurons from neural stem cells, occurs throughout life in the hippocampus of the mammalian brain and highlights the plastic nature of the mature central nervous system. Substantial evidence suggests that new neurons participate in cognitive and affective brain functions and aberrant adult neurogenesis contributes to various brain disorders. Focusing on adult hippocampal neurogenesis, we review recent findings that advance our understanding of the key properties and potential functions of adult neural stem cells. We further discuss the key evidence demonstrating the causal role of aberrant hippocampal neurogenesis and various brain disorders. Finally, we propose strategies aimed at simultaneously correcting stem cells and their niche for treating brain disorders.
MeSH term(s)	Animals ; Brain/pathology ; Brain/virology ; Brain Diseases/pathology ; Humans ; Neural Stem Cells/physiology ; Pluripotent Stem Cells/physiology ; Zika Virus/physiology
Language	English
Publishing date	2018-11-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036490-8
ISSN	1471-499X ; 1471-4914
ISSN (online)	1471-499X
ISSN	1471-4914
DOI	10.1016/j.molmed.2018.10.001
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