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Cited by 117Stress Responses and CortisolTryptophan and brain disordersNeuroinflammation and Neurodegeneration Mechanisms

Repeated stress induces a pro-inflammatory state, increases amygdala neuronal and microglial activation, and causes anxiety in adult male rats

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Munshi, Soumyabrata, Loh, Maxine K., Ferrara, Nicole, DeJoseph, M. Regina, Ritger, Alexandra, Padival, Mallika, Record, Matthew J., Urban, Janice H. +1 more·2020·Brain, Behavior, and Immunity
DOI 10.1016/j.bbi.2019.11.023PMC PMC7010555
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Abstract

A link exists between immune function and psychiatric conditions, particularly depressive and anxiety disorders. Psychological stress is a powerful trigger for these disorders and stress influences immune state. However, the nature of peripheral immune changes after stress conflicts across studies, perhaps due to the focus on few measures of pro-inflammatory or anti-inflammatory processes. The basolateral amygdala (BLA) is critical for emotion, and plays an important role in the effects of stress on anxiety. As such, it may be a primary central nervous system (CNS) mediator for the effects of peripheral immune changes on anxiety after stress. Therefore, this study aimed to delineate the influence of stress on peripheral pro-inflammatory and anti-inflammatory aspects, BLA immune activation, and its impact on BLA neuronal activity. To produce a more encompassing view of peripheral immune changes, this study used a less restrictive approach to categorize and group peripheral immune changes. We found that repeated social defeat stress in adult male Sprague-Dawley rats increased the frequencies of mature T-cells positive for intracellular type 2-like cytokine and serum pro-inflammatory cytokines. Principal component analysis and hierarchical clustering was used to guide grouping of T-cells and cytokines, producing unique profiles. Stress shifted the balance towards a specific set that included mostly type 2-like T-cells and pro-inflammatory cytokines. Within the CNS component, repeated stress caused an increase of activated microglia in the BLA, increased anxiety-like behaviors across several assays, and increased BLA neuronal firing in vivo that was prevented by blockade of microglia activation. Because repeated stress can trigger anxiety states by actions in the BLA, and altered immune function can trigger anxiety, these results suggest that repeated stress may trigger anxiety-like behaviors by inducing a pro-inflammatory state in the periphery and the BLA. These results begin to uncover how stress may recruit the immune system to alter the function of brain regions critical to emotion.

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Cited by

Sorted by citations

Authors
Munshi, S., Loh, M. K., Ferrara, N., DeJoseph, M. R., Ritger, A., Padival, M., Record, M. J., Urban, J. H., & Rosenkranz, J. A.
Affiliations
Rosalind Franklin University of Medicine and Science (US)
Corresponding author
Rosenkranz, J. Amiel
ORCID
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2020-02
Volume
84
Pages
180-199
ISSN
0889-1591 (ISSN-L)
DOI
10.1016/j.bbi.2019.11.023
PMC
PMC7010555
OpenAlex
W2991472450
Cited by
117
References
40
Citations by year
2026: 16 · 2025: 26 · 2024: 24 · 2023: 17 · 2022: 14 · 2021: 11 · 2020: 9
FWCI
5.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
repeated stress, social defeat stress, anxiety-like behavior, proinflammatory state, basolateral amygdala, microglial activation, T cell activation, inflammatory cytokines, peripheral immune activation, neuroimmune interactions, neuronal firing
MeSH terms
Amygdala, Animals, Anxiety, Male, Stress, Psychological, Rats, Sprague-Dawley, Rats, Long-Evans, Rats

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