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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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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Pharmacological antagonism of the receptor targets for HMGB-1 blocked the effect of stress to prime microglia.
“Pharmacological antagonism of the receptor targets for HMGB-1 blocked the effect of stress to prime microglia (Weber et al, 2013(Weber et al, , 2015)).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Weber et al, 2013
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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)
- PMC
- PMC3810175
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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