Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions
Abstract
The current study, in parallel experiments, evaluated the impact of chronic psychological stress on physiological and behavioural measures, and on the activation status of microglia in 15 stress-responsive brain regions. Rats were subjected, for 14 days, to two 30 min sessions of restraint per day, applied at random times each day. In one experiment the effects of stress on sucrose preference, weight gain, core body temperature, and struggling behaviour during restraint, were determined. In the second experiment we used immunohistochemistry to investigate stress-induced changes in ionized calcium-binding adaptor molecule-1 (Iba1), a marker constitutively expressed by microglia, and major histocompatibility complex-II (MHC-II), a marker often expressed on activated microglia, in a total of 15 stress-responsive nuclei. We also investigated cellular proliferation in these regions using Ki67 immunolabelling, to check for the possibility of microglial proliferation. Collectively, the results we obtained showed that chronic stress induced a significant increase in anhedonia, a decrease in weight gain across the entire observation period, a significant elevation in core body temperature during restraint, and a progressive decrease in struggling behaviour within and over sessions. With regard to microglial activation, chronic stress induced a significant increase in the density of Iba1 immunolabelling (nine of 15 regions) and the number of Iba1-positive cells (eight of 15 regions). Within the regions that exhibited an increased number of Iba1-positive cells after chronic stress, we found no evidence of a between group difference in the number of MHC-II or Ki67 positive cells. In summary, these results clearly demonstrate that chronic stress selectively increases the number of microglia in certain stress-sensitive brain regions, and also causes a marked transition of microglia from a ramified-resting state to a non-resting state. These findings are consistent with the view that microglial activation could play an important role in controlling and/or adapting to stress.
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Early life immune activation and chronic stress alter microglial density and morphology, especially in emotion-related brain regions.
“For example, early life exposure to immune activation and exposure to chronic stress alter the density and morphology of microglia, particularly in regions of the brain involved in emotion and emotion regulation (Bilbo and Schwarz, 2012; Tynan et al., 2010).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Tynan et al., 2010
Anhedonia caused by high-fat diet or restraint stress is associated with increased ionized calcium-binding adaptor molecule 1-positive microglia in several brain regions including the NAc.
“Anhedonia caused by high-fat diet or restraint stress is associated with increased ionized calcium-binding adaptor molecule 1-positive microglia in several brain regions including the NAc [189, 190].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [189]
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- Authors
- Tynan, R. J., Naicker, S., Hinwood, M., Nalivaiko, E., Buller, K. M., Pow, D. V., Day, T. A., & Walker, F. R.
- Affiliations
- Hunter Medical Research Institute (AU)
- The University of Queensland (AU)
- Corresponding author
- Day, Trevor A.
- Walker, Frederick R.
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 24
- Issue
- 7
- Pages
- 1058-1068
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2087146795
- Cited by
- 531
- References
- 66
- Citations by year
- 2026: 24 · 2025: 28 · 2024: 38 · 2023: 31 · 2022: 46 · 2021: 48 · 2020: 42 · 2019: 45 · 2018: 34 · 2017: 41 · 2016: 29 · 2015: 30 · 2014: 27 · 2013: 27 · 2012: 22
- FWCI
- 12.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- 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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- chronic psychological stress, microglial activation, microglial density, microglial morphology, restraint stress, Iba1, Ki-67, microglial proliferation, anhedonia, sucrose preference, weight gain, core body temperature
- MeSH terms
- Animals, Behavior, Animal, Body Temperature, Brain, Calcium-Binding Proteins, Chronic Disease, Food Preferences, Genes, MHC Class II, Immunohistochemistry, Male, Microfilament Proteins, Stress, Psychological, Time Factors, Weight Gain, Rats, Sprague-Dawley, Microglia, Ki-67 Antigen, Cell Proliferation, Rats
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