Cited by 93Neuroinflammation and Neurodegeneration MechanismsStress Responses and CortisolImmune Response and Inflammation

Blocking toll-like receptor 2 and 4 signaling during a stressor prevents stress-induced priming of neuroinflammatory responses to a subsequent immune challenge

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Weber, Michael D., Frank, Matthew G., Sobesky, Julia L., Watkins, Linda R., Maier, Steven F.·2013·Brain, Behavior, and Immunity

Abstract

Acute and chronic stressors sensitize or prime the neuroinflammatory response to a subsequent peripheral or central immunologic challenge. However, the neuroimmune process(es) by which stressors prime or sensitize subsequent neuroinflammatory responses remains unclear. Prior evidence suggested that toll-like receptors (TLRs) might be involved in the mediation of primed neuroinflammatory responses, but the role of TLRs during a stressor has never been directly tested. Here, a novel TLR2 and TLR4 antagonist, OxPAPC, was used to probe the contribution of TLRs in the stress sensitization phenomenon. OxPAPC has not previously been administered to the brain, and so its action in blocking TLR2 and TLR4 action in brain was first verified. Administration of OxPAPC into the CNS prior to stress prevented the stress-induced potentiation of hippocampal pro-inflammatory response to a subsequent peripheral LPS challenge occurring 24 h later. In addition, in vivo administration of OxPAPC prior to stress prevented the sensitized pro-inflammatory response from isolated microglia following administration of LPS ex vivo, further implicating microglia as a key neuroimmune substrate that mediates stress-induced sensitized neuroinflammation.

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Crossref · 10.1016/j.bbi.2013.03.004

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Authors
Weber, M. D., Frank, M. G., Sobesky, J. L., Watkins, L. R., & Maier, S. F.
Affiliations
University of Colorado Boulder (US)
Corresponding author
Weber, Michael D.
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2013-08
Volume
32
Pages
112-121
ISSN
0889-1591 (ISSN-L)
OpenAlex
W2035299031
Cited by
93
References
53
Citations by year
2026: 4 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 8 · 2018: 5 · 2017: 11 · 2016: 12 · 2015: 13 · 2014: 6 · 2013: 1
FWCI
5.99
Type
journal article
Language
en
Open access
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (R21MH096224)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
TLR2, TLR4, OxPAPC, TLR antagonists, psychological stress, stress sensitization, neuroinflammation, neuroimmune interactions, microglia, lipopolysaccharide, hippocampus, pro-inflammatory response
MeSH terms
Animals, Cisterna Magna, Electroshock, Hippocampus, Immunity, Innate, Inflammation, Injections, Lipopolysaccharides, Male, Phosphatidylcholines, Stress, Psychological, Neuroimmunomodulation, Cytokines, Rats, Sprague-Dawley, Toll-Like Receptor 2, Toll-Like Receptor 4, Rats, Interleukin-1beta, Real-Time Polymerase Chain Reaction

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