Chronic stress-induced disruption of the astrocyte network is driven by structural atrophy and not loss of astrocytes
Abstract
Chronic stress is well recognized to decrease the number of GFAP⁺ astrocytes within the prefrontal cortex (PFC). Recent research, however, has suggested that our understanding of how stress alters astrocytes may be incomplete. Specifically, chronic stress has been shown to induce a unique form of microglial remodelling, but it is not yet clear whether astrocytes also undergo similar structural modifications. Such alterations may be significant given the role of astrocytes in modulating synaptic function. Accordingly, in the current study we have examined changes in astrocyte morphology following exposure to chronic stress in adult rats, using three-dimensional digital reconstructions of astrocytes. Our analysis indicated that chronic stress produced profound atrophy of astrocyte process length, branching and volume. We additionally examined changes in astrocyte-specific S100β, which are both a putative astrocyte marker and a protein whose expression is associated with astrocyte distress. While we found that S100β levels were increased by stress, this increase was not correlated with atrophy. We further established that while chronic stress was associated with a decrease in astrocyte numbers when GFAP labelling was used as a marker, we could find no evidence of a decrease in the total number of cells, based on Nissl staining, or in the number of S100β⁺ cells. This finding suggests that chronic stress may not actually reduce astrocyte numbers and may instead selectively decrease GFAP expression. The results of the current study are significant as they indicate stress-induced astrocyte-mediated disturbances may not be due to a loss of cells but rather due to significant remodeling of the astrocyte network.
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Stress diminishes adult neurogenesis and impairs hippocampal function, reduces the size and number of astrocytes, and triggers microglial reactivity.
“Stress, on the other hand, which diminishes adult neurogenesis and impairs hippocampal function, has been shown to reduce the size and number of astrocytes (Czéh et al., 2006; Tynan et al., 2013) as well as trigger microglial reactivity (Kreisel et al., 2014; Llorens-Martín et al., 2016).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Tynan et al., 2013
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Self-citation
- Authors
- Tynan, R. J., Beynon, S. B., Hinwood, M., Johnson, S. J., Nilsson, M., Woods, J. J., & Walker, F. R.
- Affiliations
- University of Newcastle Australia (AU)
- Hunter Medical Research Institute (AU)
- Corresponding author
- Walker, Frederick R.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2013-03-20
- Volume
- 126
- Issue
- 1
- Pages
- 75-91
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2078181370
- Cited by
- 199
- References
- 63
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 30 · 2023: 12 · 2022: 17 · 2021: 17 · 2020: 17 · 2019: 21 · 2018: 16 · 2017: 13 · 2016: 12 · 2015: 14 · 2014: 5 · 2013: 6
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Funders
- Hunter Medical Research Institute
- National Health Research Institutes
- National Health and Medical Research Council
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- chronic stress, astrocytes, astrocyte morphology, glial fibrillary acidic protein, S100β, prefrontal cortex, astrocyte loss
- MeSH terms
- Animals, Astrocytes, Atrophy, Brain, Cell Count, Chronic Disease, Disease Models, Animal, Glial Fibrillary Acidic Protein, Male, Stress, Psychological, Rats, Sprague-Dawley, Imaging, Three-Dimensional, Rats, Neuroimaging
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