Evidence map›Paper›PMID 39304952›Full record

ArticleJournal of neuroinflammation2024

Repeated LPS induces training and tolerance of microglial responses across brain regions.

Jennifer Kim, Olivia Sullivan, Kristen Lee, Justin Jao, Juan Tamayo, Abdullah Muhammad Madany, Brandon Wong, Paul Ashwood, Annie Vogel Ciernia

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed.

  1. Review
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  6. Identifying a Csmd3Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  7. Prolonged systemic inflammation worsens impairments to astrocyte CaAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  8. Article
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  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. iScience · 2026
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Jennifer KimGraduate Program in Neuroscience, University of British Columbia, Vancouver, Canada.
Olivia SullivanGraduate Program in Neuroscience, University of British Columbia, Vancouver, Canada.
Kristen LeeDjavad Mowafaghian Centre for Brain Health, Vancouver, Canada.
Justin JaoDjavad Mowafaghian Centre for Brain Health, Vancouver, Canada.
Juan TamayoMIND Institute, University of California Davis, Davis, USA.
Abdullah Muhammad MadanyMIND Institute, University of California Davis, Davis, USA.
Brandon WongDjavad Mowafaghian Centre for Brain Health, Vancouver, Canada.
Paul AshwoodMIND Institute, University of California Davis, Davis, USA.
Annie Vogel CierniaGraduate Program in Neuroscience, University of British Columbia, Vancouver, Canada. annie.ciernia@ubc.ca.

Funding

Immune regulation and autismR01MH118209 · NIMH · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ASHWOOD, PAUL · 2019 to 2023
$2.0M
Immune regulation and gastrointestinal co-morbidity in autism spectrum disordersR01HD090214 · NICHD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ASHWOOD, PAUL · 2018 to 2022
$1.9M
Combined environmental exposures and neurodevelopment disordersR21ES035969 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ASHWOOD, PAUL · 2024 to 2025
$443k
The effects of wildfire exposure on maternal allergic asthma and consequences on neurobiologyR21ES035492 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ASHWOOD, PAUL · 2023 to 2023
$441k
Maternal asthma and brain developmentR21MH116383 · NIMH · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ASHWOOD, PAUL · 2018 to 2019
$432k
Brain Canada Foundation AWD-023132CIHR AWD-025853CIHR AWD-025854CIHR CRC-RS 950-232402Michael Smith Health Research BC AWD-005509National Institutes of Child Health R01HD090214Natural Sciences and Engineering Research Council of Canada DGECR-2019-00069Natural Sciences and Engineering Research Council of Canada RGPIN-2019-04450NICHD NIH HHS R01 HD090214NIEHS NIH HHS R21 ES035492NIEHS NIH HHS R21ES035492NIEHS NIH HHS R21 ES035969NIEHS NIH HHS R21ES035969NIMH NIH HHS R01 MH118209NIMH NIH HHS R01MH118209NIMH NIH HHS R21 MH116383NIMH NIH HHS R21MH116383Scottish Rite Charitable Foundation of Canada 21103
6 · The paper itself

Abstract

backgroundNeuroinflammation is involved in the pathogenesis of almost every central nervous system disorder. As the brain's innate immune cells, microglia fine tune their activity to a dynamic brain environment. Previous studies have shown that repeated bouts of peripheral inflammation can trigger long-term changes in microglial gene expression and function, a form of innate immune memory. METHODS AND

resultsIn this study, we used multiple low-dose lipopolysaccharide (LPS) injections in adult mice to study the acute cytokine, transcriptomic, and microglia morphological changes that contribute to the formation of immune memory in the frontal cortex, hippocampus, and striatum, as well as the long-term effects of these changes on behavior. Training and tolerance of gene expression was shared across regions, and we identified 3 unique clusters of DEGs (2xLPS-sensitive, 4xLPS-sensitive, LPS-decreased) enriched for different biological functions. 2xLPS-sensitive DEG promoters were enriched for binding sites for IRF and NFkB family transcription factors, two key regulators of innate immune memory. We quantified shifts in microglia morphological populations and found that while the proportion of ramified and rod-like microglia mostly remained consistent within brain regions and sexes with LPS treatment, there was a shift from ameboid towards hypertrophic morphological states across immune memory states and a dynamic emergence and resolution of events of microglia aligning end-to-end with repeated LPS.

conclusionsTogether, findings support the dynamic regulation of microglia during the formation of immune memories in the brain and support future work to exploit this model in brain disease contexts.

Indexed as

BrainLipopolysaccharidesMice, Inbred C57BLMicrogliaAnimalsCytokinesFemaleMaleMiceCytokinesLipopolysaccharidesGene expressionGene regulationInnate immune memoryMicrogliaMicroglia morphology

Identifiers

PMID39304952
PMCPMC11414187

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.