Cited by 111Advanced Glycation End Products researchAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Microglial Receptor for Advanced Glycation End Product-Dependent Signal Pathway Drives β-Amyloid-Induced Synaptic Depression and Long-Term Depression Impairment in Entorhinal Cortex

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Origlia, Nicola, Bonadonna, Camilla, Rosellini, Alfredo, Leznik, Elena, Arancio, Ottavio, Yan, Shirley ShiDu, Domenici, Luciano·2010·The Journal of Neuroscience

Abstract

Overproduction of β-amyloid (Aβ) is a pathologic feature of Alzheimer's disease, leading to cognitive impairment. Here, we investigated the impact of cell-specific receptor for advanced glycation end products (RAGE) on Aβ-induced entorhinal cortex (EC) synaptic dysfunction. We found both a transient depression of basal synaptic transmission and inhibition of long-term depression (LTD) after the application of Aβ in EC slices. Synaptic depression and LTD impairment induced by Aβ were rescued by functional suppression of RAGE. Remarkably, the rescue was only observed in slices from mice expressing a defective form of RAGE targeted to microglia, but not in slices from mice expressing defective RAGE targeted to neurons. Moreover, we found that the inflammatory cytokine IL-1β (interleukin-1β) and stress-activated kinases [p38 MAPK (p38 mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase)] were significantly altered and involved in RAGE signaling pathways depending on RAGE expression in neuron or microglia. These findings suggest a prominent role of microglial RAGE signaling in Aβ-induced EC synaptic dysfunction.

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Crossref · 10.1523/jneurosci.2127-10.2010

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  • Aβ binding to microglial RAGE (SR-J1) activates MAPK and NF-κB and, in 2- to 3-month-old animals, contributes to synaptic dysfunction via IL-1β release.

    “Binding of Aβ to the microglial SR-J1 (also called RAGE) activates MAPK and NF-κB and contributes to synaptic dysfunction through IL-1β release in 2- to 3-month-old animals139.”

    From Microglia in neurodegeneration (2018) · cites this paper as [139]

  • Higher levels of RAGE expression are found in neuronal, microglial, and endothelial cells in Alzheimer's disease patients compared with age-matched non-demented controls.

    “AGEs and the receptor for advanced glycation end-products (RAGE) can play an important role in AD pathogenesis as higher levels of RAGE expression in neuronal, microglial, and endothelial cells in patients with AD compared with age-matched, non- demented controls are found [43,44,45,46].”
  • AGEs cross-linked with Aβ can decrease the ability of microglia to clear plaques.

    “Furthermore, AGEs cross-linked with Aβ can also decrease the ability of microglia to clear plaques113.”

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Authors
Origlia, N., Bonadonna, C., Rosellini, A., Leznik, E., Arancio, O., Yan, S. S., & Domenici, L.
Affiliations
  • Neuroscience Institute (IT)
  • Columbia University (US)
  • University of L'Aquila (IT)
Corresponding author
Domenici, Luciano
Venue
The Journal of Neuroscience
Published
2010-08-25
Volume
30
Issue
34
Pages
11414-11425
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2015426193
Cited by
111
References
82
Citations by year
2026: 2 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 11 · 2021: 10 · 2020: 4 · 2019: 7 · 2018: 4 · 2017: 10 · 2016: 5 · 2015: 6 · 2014: 13 · 2013: 7 · 2012: 8
FWCI
3.81
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • KU ScholarWorks (University of Kansas) (submittedVersion, other-oa)
  • Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
Funders
  • American Health Assistance Foundation
  • Regione Toscana
  • National Institutes of Health
  • National Institute on Aging (P01AG017490, P01 AG 17490)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
receptor for advanced glycation end products, RAGE, amyloid-beta, Alzheimer's disease, entorhinal cortex, synaptic depression, long-term depression, microglia, synaptic dysfunction, IL-1β, p38 MAPK, JNK, neuroinflammation
MeSH terms
Receptor for Advanced Glycation End Products, Animals, Mice, Inbred C57BL, Mice, Transgenic, Neural Inhibition, Receptors, Immunologic, Signal Transduction, Amyloid beta-Peptides, Glycation End Products, Advanced, Microglia, Mice, Knockout, Entorhinal Cortex, Long-Term Synaptic Depression, Mice

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