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Stress Induces the Danger-Associated Molecular Pattern HMGB-1 in the Hippocampus of Male Sprague Dawley Rats: A Priming Stimulus of Microglia and the NLRP3 Inflammasome
Open accessAbstract
Exposure to acute and chronic stressors sensitizes the proinflammatory response of microglia to a subsequent immune challenge. However, the proximal signal by which stressors prime microglia remains unclear. Here, high mobility group box-1 (HMGB-1) protein was explored as a potential mediator of stress-induced microglial priming and whether HMGB-1 does so via the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) inflammasome. Exposure to 100 inescapable tail shocks (ISs) increased HMGB-1 and NLRP3 protein in the hippocampus and led isolated microglia to release HMGB-1 ex vivo. To determine whether HMGB-1 signaling is necessary for stress-induced sensitization of microglia, the HMGB-1 antagonist BoxA was injected into the cisterna magna before IS. Hippocampal microglia were isolated 24 h later and stimulated with LPS ex vivo to probe for stress-induced sensitization of proinflammatory responses. Previous IS potentiated gene expression of NLRP3 and proinflammatory cytokines to LPS, that is, microglia were sensitized. Treatment with BoxA abolished this effect. To determine whether HMGB-1 is sufficient to prime microglia, IS was replaced with intracerebral administration of disulfide or fully reduced HMGB-1. Intracerebral disulfide HMGB-1 mimicked the effect of the stressor, because microglia isolated from HMGB-1-treated rats expressed exaggerated NLRP3 and proinflammatory cytokine expression after LPS treatment, whereas fully reduced HMGB-1 had no effect. The present results suggest that the CNS innate immune system can respond to an acute stressor as if it were cellular damage, thereby releasing the danger signal HMGB-1 in the brain to prime microglia by acting on the NLRP3 inflammasome, in preparation for a later immune challenge.
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“We have also found that exposure to acute stress, in this case inescapable tailshock, increases NLRP3 protein in the hippocampus up to 24 h after stress treatment; however, microglial IL-1β was not increased at that time-point post stress (Weber et al, 2015).”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Weber et al, 2015
In the citing paper
“we found that intracisterna magna administration of an HMGB1 antagonist (box A) before stress exposure blocked the potentiated microglial proinflammatory response to an immune challenge ex vivo.”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Weber et al, 2015
In the citing paper
“We recently found that exposure to an acute stressor (inescapable tailshock) induces HMGB1 in the hippocampus concomitant with increased protein levels of active NF-κB and NLRP3 protein (Weber et al, 2015).”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Weber et al, 2015
In the citing paper
“treatment of hippocampal microglia with the TLR4 agonist LPS resulted in a potentiated IL-1β response in animals exposed to stress 24 h earlier, suggesting that the NLRP3 inflammasome was primed by initial stress exposure.”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Weber et al, 2015
In the citing paper
“Recently, HMGB-1 was found to be highly expressed in the CNS and was implicated in a variety of neuroinflammatory conditions (Kang et al, 2014), including stress (Weber et al, 2015).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Weber et al, 2015
In the citing paper
“For example, HMGB-1 protein is increased in the hippocampus following a series of repeated tail shock and persists for at least 24 h later (Weber et al, 2015).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Weber et al, 2015
In the citing paper
“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, 2015
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Citations
Cites
1 retracted
Yang, H., Lundbäck, P., Ottosson, L., Erlandsson-Harris, H., Venereau, E., Bianchi, M. E., Al-Abed, Y., Andersson, U., Tracey, K. J., & Antoine, D. J. (2012) · Molecular Medicine · doi:10.2119/molmed.2011.00389 · Cited by 407 · cited 3×
“Key words: DAMPS; HMGB-1; inflammasome; microglia; neuroinflammation; stress”
Self-citationRetractedGapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · cited 3×
“A detailed description of the PCR amplification protocol has been published previously (Frank et al., 2006). cDNA sequences were obtained from GenBank at the National Center for Biotechnology Information (NCBI; www.ncbi.nlm. nih.gov).”
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221 · cited 1×
“Previous reports show that disulfide HMGB-1 is sufficient to stimulate proinflammatory cytokines (Scaffidi et al., 2002; Park et al., 2004; Agalave et al., 2014).”
The Danger Model: A Renewed Sense of Self
Matzinger, P. (2002) · Science · doi:10.1126/science.1071059 · Cited by 4,205 · cited 1×
“The concept has developed that innate immune receptors discriminate between danger and non-danger rather than self and non-self (Matzinger, 2002).”
Yang, Y., Li, S., Yang, Q., Shi, Y., Zheng, M., Liu, Y., Chen, F., Song, G., Xu, H., Wan, T., et al. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000358696 · Cited by 3,263
Bauernfeind, F. G., Horvath, G. L., Stutz, A., Alnemri, E. S., MacDonald, K. L., Speert, D. P., Fernandes‐Alnemri, T., Wu, J., Monks, B. G., Fitzgerald, K. A., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901363 · Cited by 3,087 · cited 2×
“NLRP3 is induced by the transcription factor NF- B, and so we measured NF- B as an upstream NLRP3 marker (Bauernfeind et al., 2009).”
DAMPs, PAMPs and alarmins: all we need to know about danger
Bianchi, M. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0306164 · Cited by 2,794 · cited 2×
“Although TLRs on peripheral immune cells were first thought to recognize only pathogen-associated molecular patterns, more recent findings suggest that a variety of conditions can lead to the release of endogenous molecules called alarmins or dangerassociated molecular patterns (DAMPs; Bianchi, 2007) that can also sig…”
High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal
Lotze, M. T., & Tracey, K. J. (2005) · Nature reviews. Immunology · doi:10.1038/nri1594 · Cited by 2,490 · cited 2×
“However, HMGB-1 is located primarily in the nucleus and is not considered to be an alarmin unless released into the extracellular space (Lotze and Tracey, 2005).”
Self-citationThe Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436 · cited 12×
“However, the present IS paradigm does not alter IL-1 protein in the hippocampus 24 h after stressor termination (Frank et al., 2007), suggesting that the NLRP3 inflammasome is primed but not active.”
InfluentialPark, J. S., Svetkauskaite, D., He, Q., Kim, J., Strassheim, D., Ishizaka, A., & Abraham, E. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306793200 · Cited by 1,582
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Duque, É. D. A. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2019.tde-15102019-100704
“Cardona et al mostraram que a ausência dos receptores de fractalkina, CX3CR1, na microglia, aumentou a susceptibilidade à neurotoxicidade em camundongos submetidos a modelos de Parkinson, Esclerose Lateral Amiotrófica e administração sistêmica de LPS (55) e estudos mais recentes mostraram que a fractalkina induz neuro…”
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Bueno, B. G., MacDowell, K. S., Madrigal, J. L. M., & Leza, J. C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-817933-8.00001-3
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Ribeiro, D. E., Kaster, M. P., Ulrich, H., Lisboa, S. F. D. S., & Joca, S. R. L. (2023) · Springer eBooks · doi:10.1007/978-3-031-26945-5_7
Lu, C., & Xu, X. (2023) · Stress and Brain · doi:10.26599/sab.2023.9060002
Shaykin, J. D., Olyha, L. N., Doorn, C. E. V., Hales, J. D., Chandler, C. M., Hopkins, D. M., Nixon, K., Beckmann, J. S., Pauly, J. R., & Bardo, M. T. (2024) · Drug and Alcohol Dependence Reports · doi:10.1016/j.dadr.2024.100277
“A secondary purpose of this study was to assess whether adolescent EtOH exposure exacerbates EtOH-induced neurodegenerative processes in adulthood through microglial “ priming ” (Frank et al., 2012; Perry and Holmes, 2014; Weber et al., 2015).”
Background(2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23565-8.09996-8
Inflammatory Roads to Parkinson’s Disease
Anisman, H., Hayley, S. P., & Kusnecov, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23565-8.00015-6
In vitro and in vivo study of the effects of Levetiracetam on activated microglia during sepsis
Fleurance, R. (2021) · theses.fr (ABES) · doi:10.70675/0a82ed6ez6595z4366z832fz70cbe839c7ff
Zhang, H., Marquart, B. M., Holbrook, E. M., Wright, C. T. O., Zambrano, C. A., Gebert, M. J., Dawud, L. M., Andersen, N. D., Kessler, L. R., Sago, S. A., et al. (2026) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2026.106809
Self-citationProgrammed cell death pathways in human microglia: Modeling and therapeutic targeting
Koppinen, T. K., Takacs, L., Collin, L., Mracsko, E. Z., & Keaney, J. (2026) · Glial health research. · doi:10.1016/j.ghres.2026.100015
Toyoda, H. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27177597
“Importantly, this primed state can be induced in the absence of overt tissue injury [92].”
Guo, Y., Wang, W., Li, L., Lu, X., Lu, C., Zhong, X., & Guo, L. (2026) · Psychological Medicine · doi:10.1017/s0033291726105595
“…metabolism, modulate immune cell function, trigger NLRP3 inflammasome activation, promote pro-inflammatory cytokine production, and induce microglia-mediated neuroinflammation (Busillo, Azzam, & Cidlowski, 2011; Gülke, Gelderblom, & Magnus, 2018; Kivimäki et al., 2018, 2023; Weber et al., 2015).”
Seol, S.-I., Kim, J., Davaanyam, D., Park, S., Lee, E.-H., Han, P.-L., Kim, T.-K., & Lee, J.-K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198681
“In contrast, a subsequent LPS challenge 24 h later induced a disproportionately severe neuroinflammatory response, characterized by elevations in IL-1 β , IL-6, and TNF α , compared to non-stressed, LPS-treated controls [48].”
InfluentialБарасбиевич, Х. А., Мизиев, И. А., Tkhabisimova, I. K., Borukaeva, I. K., Хараева, З. Ф., Анаева, Л. А., & Лукьяева, С. А. (2026) · Лабораторная диагностика Восточная Европа · doi:10.34883/pi.2026.15.3.013
Metadata
- Authors
- Weber, M. D., Frank, M. G., Tracey, K. J., Watkins, L. R., & Maier, S. F.
- Affiliations
- University of Colorado Boulder (US)
- Northwell Health (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-01-07
- Volume
- 35
- Issue
- 1
- Pages
- 316-324
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4287150
- OpenAlex
- W2087987871
- Cited by
- 215
- References
- 46
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 12 · 2023: 11 · 2022: 20 · 2021: 21 · 2020: 25 · 2019: 19 · 2018: 24 · 2017: 25 · 2016: 21 · 2015: 16
- FWCI
- 15.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (MH096224, R21MH096224)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- HMGB1, NLRP3 inflammasome, microglial priming, hippocampus, inflammatory cytokines, lipopolysaccharide response, damage-associated molecular patterns
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Hippocampus, Male, Stress, Psychological, Rats, Sprague-Dawley, Microglia, Receptors, Cytoplasmic and Nuclear, HMGB1 Protein, Rats, Inflammasomes
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