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Cited by 126Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchTryptophan and brain disorders

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

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Prieto, G. Aleph, Snigdha, Shikha, Baglietto-Vargas, David, Smith, Erica D., Berchtold, Nicole C., Tong, Liqi, Ajami, Dariush, LaFerla, Frank M. +2 more·2015·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1514486112PMC PMC4568670
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Abstract

Significance: There is a growing understanding that inflammation impairs synaptic plasticity and cognition and that the aged brain has an elevated sensitivity to cognitive impairment by the proinflammatory cytokine interleukin 1β (IL-1β). IL-1β activates different pathways via AcP (proinflammatory) or AcPb (prosurvival) IL-1 receptor subunits. This study demonstrates that the IL-1 receptor subunit system undergoes an age-dependent reconfiguration in hippocampal synapses. This previously undescribed reconfiguration, characterized by an increase in the AcP/AcPb ratio, is responsible for potentiating impairments of synaptic plasticity and memory by IL-1β. Our data reveal a previously unidentified mechanism that explains the age-related vulnerability of hippocampal function to impairment by inflammation and adds another dimension beyond glia to understanding how inflammation causes cognitive decline in aging.

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Authors
Prieto, G. A., Snigdha, S., Baglietto-Vargas, D., Smith, E. D., Berchtold, N. C., Tong, L., Ajami, D., LaFerla, F. M., Rebek, J., & Cotman, C. W.
Affiliations
  • University of California, Irvine (US)
  • Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697;
  • Scripps Research Institute (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2015-08-24
Volume
112
Issue
36
Pages
E5078-87
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1514486112
PMC
PMC4568670
OpenAlex
W2134486111
Cited by
126
References
10
Citations by year
2026: 9 · 2025: 7 · 2024: 12 · 2023: 10 · 2022: 5 · 2021: 19 · 2020: 11 · 2019: 9 · 2018: 26 · 2017: 11 · 2016: 6 · 2015: 1
FWCI
7.21
Type
journal article
Language
en
Open access
Licence
www.pnas.org/site/misc/userlicense.xhtml (vor)
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Repositorio Institucional de la Universidad de Málaga (University of Málaga) (submittedVersion, cc-by-nc-nd)
Funders
  • HHS | NIH | National Institute on Aging (P01-AG000538, RO1-AG34667, AG027544-06)
  • Larry L. Hillblom Foundation (#2013-A-016-FEL)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
IL-1β, IL-1 receptor type 1, IL-1 receptor accessory protein, synaptic plasticity, long-term potentiation, hippocampus, aging, neuroinflammation, cognitive impairment, lipopolysaccharide, memory
MeSH terms
Age Factors, Animals, Cells, Cultured, Dose-Response Relationship, Drug, Hippocampus, Mice, Inbred C57BL, Neuronal Plasticity, Neurons, Synapses, Synaptosomes, Blotting, Western, Signal Transduction, Rats, Sprague-Dawley, Long-Term Potentiation, Brain-Derived Neurotrophic Factor, RNA Interference, Receptors, Interleukin-1 Type I, Interleukin-1 Receptor Accessory Protein, Interleukin-1beta, Mice, 129 Strain

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