Evidence map›Paper›PMID 26305968›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Synapse-specific IL-1 receptor subunit reconfiguration augments vulnerability to IL-1β in the aged hippocampus.

G Aleph Prieto, Shikha Snigdha, David Baglietto-Vargas, Erica D Smith, Nicole C Berchtold, Liqi Tong, Dariush Ajami, Frank M LaFerla, Julius Rebek, Carl W Cotman

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
8.2field-weighted citation impact, top 2% of its field
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

75 citing papers in PubMed, 124 citations in OpenAlex.

  1. Trial
  2. Article
  3. Therapeutic Administration ofInternational journal of molecular sciences · 2026
    Article
  4. Review
  5. Article
  6. Reinventing amlodipine.The Journal of pharmacology and experimental therapeutics · 2026
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Dopamine Activates the D1R-ZnCellular and molecular neurobiology · 2023
    Article
  18. Systemic inflammation, neuroinflammation and perioperative neurocognitive disorders.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Review
  19. Review
  20. Review

15 more citing papers are in PubMed but not listed here.

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

10 authors at 2 institutions in 2 countries.

G Aleph PrietoInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697; cwcotman@uci.edu aleph.prieto@uci.edu jrebek@scripps.edu.
Shikha SnigdhaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;
David Baglietto-VargasInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;
Erica D SmithInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;
Nicole C BerchtoldInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;
Liqi TongInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;
Dariush AjamiSkaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037;
Frank M LaFerlaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;
Julius RebekSkaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Chemistry, Fudan University, Shanghai, 200433 China cwcotman@uci.edu aleph.prieto@uci.edu jrebek@scripps.edu.
Carl W CotmanInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697; cwcotman@uci.edu aleph.prieto@uci.edu jrebek@scripps.edu.
University of California, Irvine · USScripps Research Institute · US

Funding

TISSUE REPOSITORY COREP01AG000538 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 1985 to 2018
$24.8M
Learning and Memory Impairments in Transgenic AD ModelsR01AG027544 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2007 to 2016
$3.1M
Gene Expression, Compensation Mechanisms, and Successful Cognitive AgingR01AG034667 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI COTMAN, CARL WAYNE · 2009 to 2013
$1.7M
NIA NIH HHS AG027544-06NIA NIH HHS P01 AG000538NIA NIH HHS P01-AG000538NIA NIH HHS R01 AG027544NIA NIH HHS R01 AG034667NIA NIH HHS R01-AG34667
6 · The paper itself

Abstract

In the aged brain, synaptic plasticity and memory show increased vulnerability to impairment by the inflammatory cytokine interleukin 1β (IL-1β). In this study, we evaluated the possibility that synapses may directly undergo maladaptive changes with age that augment sensitivity to IL-1β impairment. In hippocampal neuronal cultures, IL-1β increased the expression of the IL-1 receptor type 1 and the accessory coreceptor AcP (proinflammatory), but not of the AcPb (prosurvival) subunit, a reconfiguration that potentiates the responsiveness of neurons to IL-1β. To evaluate whether synapses develop a similar heightened sensitivity to IL-1β with age, we used an assay to track long-term potentiation (LTP) in synaptosomes. We found that IL-1β impairs LTP directly at the synapse and that sensitivity to IL-1β is augmented in aged hippocampal synapses. The increased synaptic sensitivity to IL-1β was due to IL-1 receptor subunit reconfiguration, characterized by a shift in the AcP/AcPb ratio, paralleling our culture data. We suggest that the age-related increase in brain IL-1β levels drives a shift in IL-1 receptor configuration, thus heightening the sensitivity to IL-1β. Accordingly, selective blocking of AcP-dependent signaling with Toll-IL-1 receptor domain peptidomimetics prevented IL-1β-mediated LTP suppression and blocked the memory impairment induced in aged mice by peripheral immune challenge (bacterial lipopolysaccharide). Overall, this study demonstrates that increased AcP signaling, specifically at the synapse, underlies the augmented vulnerability to cognitive impairment by IL-1β that occurs with age.

Indexed as

Age FactorsAnimalsBlotting, WesternBrain-Derived Neurotrophic FactorCells, CulturedDose-Response Relationship, DrugHippocampusInterleukin-1betaInterleukin-1 Receptor Accessory ProteinLong-Term PotentiationMice, 129 StrainMice, Inbred C57BLNeuronal PlasticityNeuronsRats, Sprague-DawleyReceptors, Interleukin-1 Type IBrain-Derived Neurotrophic FactorInterleukin-1betaInterleukin-1 Receptor Accessory ProteinReceptors, Interleukin-1 Type IAcPAcPbLTPneuroinflammationreceptor sensitivity

Identifiers

PMID26305968
PMCPMC4568670
OpenAlexW2134486111

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.