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Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

Astrocytes are essential for the development and homeostatic maintenance of the central nervous system (CNS). They are also critical players in the CNS injury response during which they undergo a process referred to as “reactive astrogliosis.” Diversity in astrocyte morphology and gene expression, a...

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Autores principales: Moulson, Aaron J., Squair, Jordan W., Franklin, Robin J. M., Tetzlaff, Wolfram, Assinck, Peggy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349991/
https://www.ncbi.nlm.nih.gov/pubmed/34381334
http://dx.doi.org/10.3389/fncel.2021.703810
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author Moulson, Aaron J.
Squair, Jordan W.
Franklin, Robin J. M.
Tetzlaff, Wolfram
Assinck, Peggy
author_facet Moulson, Aaron J.
Squair, Jordan W.
Franklin, Robin J. M.
Tetzlaff, Wolfram
Assinck, Peggy
author_sort Moulson, Aaron J.
collection PubMed
description Astrocytes are essential for the development and homeostatic maintenance of the central nervous system (CNS). They are also critical players in the CNS injury response during which they undergo a process referred to as “reactive astrogliosis.” Diversity in astrocyte morphology and gene expression, as revealed by transcriptional analysis, is well-recognized and has been reported in several CNS pathologies, including ischemic stroke, CNS demyelination, and traumatic injury. This diversity appears unique to the specific pathology, with significant variance across temporal, topographical, age, and sex-specific variables. Despite this, there is limited functional data corroborating this diversity. Furthermore, as reactive astrocytes display significant environmental-dependent plasticity and fate-mapping data on astrocyte subsets in the adult CNS is limited, it remains unclear whether this diversity represents heterogeneity or plasticity. As astrocytes are important for neuronal survival and CNS function post-injury, establishing to what extent this diversity reflects distinct established heterogeneous astrocyte subpopulations vs. environmentally dependent plasticity within established astrocyte subsets will be critical for guiding therapeutic development. To that end, we review the current state of knowledge on astrocyte diversity in the context of three representative CNS pathologies: ischemic stroke, demyelination, and traumatic injury, with the goal of identifying key limitations in our current knowledge and suggesting future areas of research needed to address them. We suggest that the majority of identified astrocyte diversity in CNS pathologies to date represents plasticity in response to dynamically changing post-injury environments as opposed to heterogeneity, an important consideration for the understanding of disease pathogenesis and the development of therapeutic interventions.
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spelling pubmed-83499912021-08-10 Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity? Moulson, Aaron J. Squair, Jordan W. Franklin, Robin J. M. Tetzlaff, Wolfram Assinck, Peggy Front Cell Neurosci Neuroscience Astrocytes are essential for the development and homeostatic maintenance of the central nervous system (CNS). They are also critical players in the CNS injury response during which they undergo a process referred to as “reactive astrogliosis.” Diversity in astrocyte morphology and gene expression, as revealed by transcriptional analysis, is well-recognized and has been reported in several CNS pathologies, including ischemic stroke, CNS demyelination, and traumatic injury. This diversity appears unique to the specific pathology, with significant variance across temporal, topographical, age, and sex-specific variables. Despite this, there is limited functional data corroborating this diversity. Furthermore, as reactive astrocytes display significant environmental-dependent plasticity and fate-mapping data on astrocyte subsets in the adult CNS is limited, it remains unclear whether this diversity represents heterogeneity or plasticity. As astrocytes are important for neuronal survival and CNS function post-injury, establishing to what extent this diversity reflects distinct established heterogeneous astrocyte subpopulations vs. environmentally dependent plasticity within established astrocyte subsets will be critical for guiding therapeutic development. To that end, we review the current state of knowledge on astrocyte diversity in the context of three representative CNS pathologies: ischemic stroke, demyelination, and traumatic injury, with the goal of identifying key limitations in our current knowledge and suggesting future areas of research needed to address them. We suggest that the majority of identified astrocyte diversity in CNS pathologies to date represents plasticity in response to dynamically changing post-injury environments as opposed to heterogeneity, an important consideration for the understanding of disease pathogenesis and the development of therapeutic interventions. Frontiers Media S.A. 2021-07-26 /pmc/articles/PMC8349991/ /pubmed/34381334 http://dx.doi.org/10.3389/fncel.2021.703810 Text en Copyright © 2021 Moulson, Squair, Franklin, Tetzlaff and Assinck. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Moulson, Aaron J.
Squair, Jordan W.
Franklin, Robin J. M.
Tetzlaff, Wolfram
Assinck, Peggy
Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?
title Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?
title_full Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?
title_fullStr Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?
title_full_unstemmed Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?
title_short Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?
title_sort diversity of reactive astrogliosis in cns pathology: heterogeneity or plasticity?
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349991/
https://www.ncbi.nlm.nih.gov/pubmed/34381334
http://dx.doi.org/10.3389/fncel.2021.703810
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