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Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury
Open accessAbstract
Reactive astrocytes in neurotrauma, stroke, or neurodegeneration are thought to undergo cellular hypertrophy, based on their morphological appearance revealed by immunohistochemical detection of glial fibrillary acidic protein, vimentin, or nestin, all of them forming intermediate filaments, a part of the cytoskeleton. Here, we used a recently established dye-filling method to reveal the full three-dimensional shape of astrocytes assessing the morphology of reactive astrocytes in two neurotrauma models. Both in the denervated hippocampal region and the lesioned cerebral cortex, reactive astrocytes increased the thickness of their main cellular processes but did not extend to occupy a greater volume of tissue than nonreactive astrocytes. Despite this hypertrophy of glial fibrillary acidic protein-containing cellular processes, interdigitation between adjacent hippocampal astrocytes remained minimal. This work helps to redefine the century-old concept of hypertrophy of reactive astrocytes.
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“Astrocytes are activated in response to acute or chronic central nervous system injury. The activated state is characterized by hypertrophy of proximal processes and up-regulation of the intermediate filament (nanofilament) proteins glial fibrillary acid protein (GFAP) and vimentin (Vim) (15, 16).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [16]
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“Increased GFAP immunoreactivity largely reflects changes in the astrocytic cytoskeleton and tends to exaggerate the degree of hypertrophy because, with the exception of scar-border astrocytes, the volume accessed by reactive astrocytes does not change, as they remain in their territorial domains23.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [23]
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“Because immunostaining with individual antibodies cannot reveal the full extent of astrocyte morphology (16), we expressed GFP in astrocytes in vivo to observe the complete cellular profile of the cells.”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [16]
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“Further, dye-filling methods can be used to visualize whole astrocytes in mice23, as well as in human brain samples from surgical resections (Fig. 1b)24.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [23]
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“Regarding the form of astrocytes, reactive astrocytes are an activated form of astrocytes in response to toxic materials [49].”
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Activation of Astrocytes in Neurodegenerative Diseases
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Immunopharmacology of Alzheimer’s disease
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Astrocyte heterogeneity under physiological conditions and after brain injury
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Etude des interactions entre neurones et astrocytes au sein de la substance noire réticulée
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“Ce phénomène peut avoir des effets bénéfiques, comme l’augmentation de la recapture du glutamate ou néfastes comme la perturbation de l’activité neuronale (Wilhelmsson et al., 2006; Barres, 2008; Chvatal et al., 2008; Ortinski et al.).”
Background
Metadata
- Authors
- Wilhelmsson, U., Bushong, E. A., Price, D. L., Smarr, B. L., Phung, V., Terada, M., Ellisman, M. H., & Pekny, M.
- Affiliations
- University of Gothenburg (SE)
- University of California San Diego (US)
- Corresponding author
- Pekny, Milos
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-11-14
- Volume
- 103
- Issue
- 46
- Pages
- 17513-17518
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1859960
- OpenAlex
- W1969305530
- Cited by
- 643
- References
- 34
- Citations by year
- 2026: 17 · 2025: 33 · 2024: 41 · 2023: 45 · 2022: 40 · 2021: 56 · 2020: 35 · 2019: 36 · 2018: 40 · 2017: 40 · 2016: 35 · 2015: 42 · 2014: 35 · 2013: 30 · 2012: 30
- FWCI
- 10.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA4084314)
- National Institute of Neurological Disorders and Stroke (R01NS014718, NS046068, R01NS046068, NS014718)
- National Center for Research Resources (P41RR004050, RR004050)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- reactive astrocytes, astrocyte hypertrophy, astrocyte morphology, glial fibrillary acidic protein, intermediate filaments, neurotrauma, cerebral cortex lesions
- MeSH terms
- Animals, Astrocytes, Brain Injuries, Female, Cell Shape, Mice
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