Evidence that Microglia Mediate the Neurobiological Effects of Chronic Psychological Stress on the Medial Prefrontal Cortex
Abstract
Psychological stress contributes to the development of clinical depression. This has prompted many preclinical studies to investigate the neurobiology of this relationship, however, the effects of stress on glia remain unclear. In this study, we wished to determine, first, how exposure to chronic psychological stress affects microglial activity within the prefrontal cortex (PFC) and, second, whether the observed changes were meaningfully related to corresponding changes in local neuronal activity and PFC-regulated behavior. Therefore, we examined markers of microglial activation, antigen presentation, apoptosis, and persistent neuronal activation within the PFC after exposure to repeated restraint stress. We also examined the effect of stress on spatial working memory, a PFC-dependent function. Finally, we tested the ability of a microglial activation inhibitor (minocycline) to alter the impact of chronic stress on all of these endpoints. Stressor exposure produced positively correlated increases in microglial and long-term neuronal activation in the PFC but not antigen presentation or apoptosis. As expected, it also impaired spatial working memory. Importantly, minocycline reduced the impact of stress on neuronal activation and working memory, as well as microglial activation. These results suggest a role for microglia in mediating the effects of stress on PFC neuronal function and PFC-regulated behavior.
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Inhibiting microglia during stress exposure with minocycline attenuated the increase of proinflammatory cytokines normally produced by stress and protected against stress-associated deficits in cognitive memory tasks and depressive-like and anxiety-like behaviors.
“In each case, inhibiting microglia during stress exposure attenuated the increase of proinflammatory cytokines normally produced by stress (Hinwood et al, 2012(Hinwood et al, , 2013;;Kreisel et al, 2014;McKim et al, 2016).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Hinwood et al, 2012
Microglial activation and inflammatory signaling following psychological stress has been reported in mice and rats alike, and has also been recapitulated in other models, such as restraint stress and foot-shock stress.
“Microglial activation and inflammatory signaling following psychological stress has been reported in mice and rats alike, and has also been recapitulated in other models, such as restraint stress and foot-shock stress (Frank et al, 2007;Hinwood et al, 2012;Kreisel et al, 2014;Tynan et al, 2010;Voorhees et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Hinwood et al, 2012
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- Authors
- Hinwood, M., Morandini, J., Day, T. A., & Walker, F. R.
- Affiliations
- Hunter Medical Research Institute (AU)
- Corresponding author
- Hinwood, M.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-08-30
- Volume
- 22
- Issue
- 6
- Pages
- 1442-1454
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2132867079
- Cited by
- 420
- References
- 82
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 32 · 2023: 24 · 2022: 31 · 2021: 41 · 2020: 25 · 2019: 24 · 2018: 28 · 2017: 35 · 2016: 33 · 2015: 31 · 2014: 29 · 2013: 28 · 2012: 26
- FWCI
- 14.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Own your potential (DEAKIN) (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- 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
- microglia, chronic psychological stress, medial prefrontal cortex, depression, restraint stress, minocycline, microglial activation, neuronal activation, spatial working memory, antigen presentation, apoptosis, neuroinflammation
- MeSH terms
- Animals, Chronic Disease, Male, Stress, Psychological, Rats, Sprague-Dawley, Prefrontal Cortex, Microglia, Maze Learning, Rats
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