Cited by 420Neuroinflammation and Neurodegeneration MechanismsStress Responses and CortisolTryptophan and brain disorders

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Evidence that Microglia Mediate the Neurobiological Effects of Chronic Psychological Stress on the Medial Prefrontal Cortex

Hinwood, M., Morandini, J., Day, T. A., Walker, F. R.·2012·Cerebral Cortex

DOI 10.1093/cercor/bhr229

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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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Authors: Hinwood, M., Morandini, J., Day, T. A., & Walker, F. R.
Affiliations: Hunter Medical Research Institute (AU)
Corresponding author: Hinwood, M.
ORCID: Hinwood, M.
Morandini, J.
Day, T. A.
Walker, F. R.
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
DOI: 10.1093/cercor/bhr229
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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Evidence that Microglia Mediate the Neurobiological Effects of Chronic Psychological Stress on the Medial Prefrontal Cortex

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