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Astrogliosis
Open accessAbstract
In addition to their many functions in the healthy central nervous system (CNS), astrocytes respond to CNS damage and disease through a process called astrogliosis. For many decades, astrogliosis was sparsely studied and enigmatic. This article examines recent evidence supporting a definition of astrogliosis as a spectrum of heterogeneous potential changes in astrocytes that occur in a context-specific manner as determined by diverse signaling events that vary with the nature and severity of different CNS insults. Astrogliosis is associated with essential beneficial functions, but under specific circumstances can lead to harmful effects. Potential dysfunctions of astrocytes and astrogliosis are being identified that can contribute to, or be primary causes of, CNS disorders, leading to the notion of astrocytopathies. A conceptual framework is presented that allows consideration of normally occurring and dysfunctional astrogliosis and their different roles in CNS disorders.
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“The analysis of individual genes and pathways upregulated in aging astrocytes revealed changes associated with reactive astrocytes, including upregulation of Gfap, Serpina3n, the complement cascade, and cytokines (Sofroniew, 2015; Zamanian et al., 2012).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Sofroniew, 2015
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“We find that astrocytes in the aging brain exhibit gene expression changes consistent with reactive astrocytes, albeit with changes of a lesser magnitude, showing a mild to moderate level of reactivity (Sofroniew, 2015).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Sofroniew, 2015
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“Astroglia are interacting with synapses and forming part of the synapse structure [86, 87]”
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“…3 (STAT3), NF-κB, cAMP, Rho-kinase, JNK, Olig2, CEPB1 and EphB2 are involved in mediating different aspects or different degrees of astrogliosis, including cell hypertrophy, proliferation, migration and scar formation as well as up-regulation of GFAP, vimentin and nestin (Sofroniew, 2014).”
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“…reactivity produces multiple pathological phenotypes, which are context- and disease-specific, and may exert either neuroprotective or neurotoxic effects (Zamanian et al. 2012; Burda and Sofroniew 2014; Pekny and Pekna 2014; Sofroniew 2014a,b, 2015; Pekny et al. 2016; Liddelow andBarres 2017).”
BackgroundMolecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD
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Tavares, G., Martins, M., Correia, J. S., Sardinha, V. M., Guerra‐Gomes, S., das Neves, S. P., Marques, F., Sousa, N., & Oliveira, J. F. (2016) · Brain Structure and Function · doi:10.1007/s00429-016-1316-8 · Cited by 93
“This data supports previous observations (Wil-helmsson et al. 2006; Sofroniew 2015).”
BackgroundResultInfluentialNeuroinflammation Is Associated with GFAP and sTREM2 Levels in Multiple Sclerosis
Azzolini, F., Gilio, L., Pavone, L., Iezzi, E., Dolcetti, E., Bruno, A., Buttari, F., Musella, A., Mandolesi, G., Guadalupi, L., et al. (2022) · Biomolecules · doi:10.3390/biom12020222 · Cited by 94
Glaucoma: from pathogenic mechanisms to retinal glial cell response to damage
Fernández‐Albarral, J. A., Ramirez, A. I., de Hoz, R., Matamoros, J. A., Salobrar‐García, E., Elvira‐Hurtado, L., López‐Cuenca, I., Sánchez-Puebla, L., Salazar, J. J., & Ramirez, J. M. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1354569 · Cited by 105
“Astrocyte proliferation occurs after sustained exposure to damage, whether in the presence of a chronic neurodegenerative process, trauma, ischemic and infectious processes (Sofroniew, 2014).”
Mesenchymal stromal cells (MSCs) for neurodegenerative disease: A promising frontier
Shariati, A., Nemati, R., Sadeghipour, Y., Yaghoubi, Y., Baghbani, R., Javidi-Aghdam, K., Zamani, M., & Hassanzadeh, A. (2020) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2020.151097 · Cited by 95
Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?
Moulson, A. J., Squair, J. W., Franklin, R. J. M., Tetzlaff, W., & Assinck, P. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.703810 · Cited by 97
“…was long viewed as homogenous and functionally passive, consisting of a stereotyped set of changes driving the conversion of homeostatic astrocytes to a distinct phenotype—the “reactive astrocyte” (Eddleston and Mucke, 1993; Anderson et al., 2014; Pekny and Pekna, 2014; Sofroniew, 2015).”
InfluentialAstrocyte-Mediated Neuroinflammation in Neurological Conditions
Zhao, Y., Huang, Y., Cao, Y., & Yang, J. H. (2024) · Biomolecules · doi:10.3390/biom14101204 · Cited by 106
“Notably, such BBB breakage directly results in the infiltration of peripheral immune cells from the blood circulation.”
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Astrocyte Diversity: Current Insights and Future Directions
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“For example, major CNS neurotrauma such as severe traumatic brain injury or spinal cord injury provokes multifaceted neurodegenerative cascades and complex cellular and molecular responses, potentially culminating in a significant necrotic zone surrounded by a glial scar [1–3].”
Emerging evidence for astrocyte dysfunction in schizophrenia
Figueiredo, E. C. D. O., Calì, C., Petrelli, F., & Bezzi, P. (2022) · Glia · doi:10.1002/glia.24221 · Cited by 87
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Altered Waste Disposal System in Aging and Alzheimer’s Disease: Focus on Astrocytic Aquaporin-4
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“Astroglial pathological modifications are driven by different signaling mechanisms and produce diverse responses from adaptive to maladaptive, and further they may change along the course of a disease (Sofroniew, 2014; Pekny et al., 2016; Verkhratsky et al., 2017).”
BackgroundBettcher, B. M., Olson, K. E., Carlson, N. E., McConnell, B. V., Boyd, T. D., Adame, V., Solano, D. A., Anton, P. E., Markham, N. E., Thaker, A. A., et al. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.02.012 · Cited by 84
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Early effects of LPS-induced neuroinflammation on the rat hippocampal glycolytic pathway
Vizuete, A. F. K., Fróes, F. T., Seady, M., Zanotto, C., Bobermin, L. D., Roginski, A. C., Wajner, M., Quincozes‐Santos, A., & Gonçalves, C. A. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02612-w · Cited by 88
Understanding exosomes: Part 2—Emerging leaders in regenerative medicine
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Glial fibrillary acidic protein in Alzheimer’s disease: a narrative review
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“12 Initially, reactive astrogliosis is a protective process involving multiple cellular and molecular responses to CNS injury.”
Mechanisms of Blood-Brain Barrier Disruption in Herpes Simplex Encephalitis
Liu, H., Qiu, K., He, Q., Qiang, L., & Lu, W. (2018) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-018-9821-6 · Cited by 81
“However, others have shown that astrogliosis may be harmful, as in the context of inflammation (Sofroniew 2015; Sofroniew and Vinters 2010).”
Woods, R. M., Lorusso, J. M., Fletcher, J., ElTaher, H., McEwan, F., Harris, I., Kowash, H. M., D'Souza, S. W., Harte, M., Hager, R., et al. (2023) · Neuronal Signaling · doi:10.1042/ns20220064 · Cited by 87
Does neuroinflammation turn on the flame in Alzheimer's disease? Focus on astrocytes
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“In addition, these cells importantly contribute to synaptogenesis and dynamically modulate information processing and signal transmission, regulate neural and synaptic plasticity, and provide trophic and metabolic support to neurons (Perea et al., 2009; Sofroniew, 2014).”
BackgroundSodium channels in astroglia and microglia
Pappalardo, L. W., Black, J. A., & Waxman, S. G. (2016) · Glia · doi:10.1002/glia.22967 · Cited by 87
Role and Therapeutic Potential of Astrocytes in Amyotrophic Lateral Sclerosis
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Redox Signaling, Neuroinflammation, and Neurodegeneration
Aguilera, G., Colín-González, A. L., Rangel‐López, E., Chavarría, A., & Santamaría, A. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7099 · Cited by 81
“Oneormoreoftheprocessesmentionedearlierderiveina response that is known formally as reactive gliosis (88, 225), a state that exhibits a complex nature and holds the potential to interrelate by many molecular signaling mechanisms (22, 226).”
Metadata
- Authors
- Sofroniew, M. V.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Sofroniew, Michael V.
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2014-11-07
- Volume
- 7
- Issue
- 2
- Pages
- a020420
- ISSN
- 1943-0264 (ISSN-L)
- PMC
- PMC4315924
- OpenAlex
- W4239346618
- Cited by
- 695
- References
- 109
- Citations by year
- 2026: 44 · 2025: 53 · 2024: 84 · 2023: 83 · 2022: 101 · 2021: 83 · 2020: 86 · 2019: 61 · 2018: 38 · 2017: 27 · 2016: 21 · 2015: 13 · 2014: 1
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- astrocyte activation, astrocytes, astrocytopathy, central nervous system injury, central nervous system disorders, astrocyte dysfunction
- MeSH terms
- Astrocytes, Cell Communication, Cell Movement, Central Nervous System, Central Nervous System Diseases, Cicatrix, Models, Biological, Mutation, Signal Transduction
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