Cited by 202Neuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and TreatmentsTryptophan and brain disorders

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Fractalkine‐induced activation of the phosphatidylinositol‐3 kinase pathway attentuates microglial activation in vivo and in vitro

Lyons, Anthony, Lynch, Aileen M., Downer, Eric J., Hanley, Riona, O’Sullivan, Joan B., Smith, Andrew, Lynch, Marina A.·2009·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.2009.06253.x

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Abstract

Several neurodegenerative disorders are associated with evidence of inflammation, one feature of which is increased activation of microglia, the most likely cellular source of inflammatory cytokines like interleukin‐1β. It is now recognized that interaction of microglia with other cells contributes to maintenance of microglia in a quiescent state and the complementary distribution of the chemokine, fractalkine (CX 3 CL1) on neurons and its receptor (CX 3 CR1) on microglia, suggests that this interaction may play a role in modulating microglial activation. Here we demonstrate that both soluble and membrane‐bound fractalkine attenuate lipopolysaccharide‐induced microglial activation in vitro. We also show that fractalkine expression is reduced in the brain of aged rats and this is accompanied by an age‐related increase in microglial activation. Treatment of aged rats with fractalkine attenuates the age‐related increase in microglial activation and the evidence indicates that fractalkine‐induced activation of the phosphatidylinositol‐3 kinase pathway is required to maintain microglia in a quiescent state both in vivo and in vitro.

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Authors: Lyons, A., Lynch, A. M., Downer, E. J., Hanley, R., O’Sullivan, J. B., Smith, A., & Lynch, M. A.
Affiliations: Trinity College Dublin (IE)
Corresponding author: Lynch, Marina A.
ORCID: Lynch, Aileen M.
Downer, Eric J.
Lynch, Marina A.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2009-08-10
Volume: 110
Issue: 5
Pages: 1547-1556
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/j.1471-4159.2009.06253.x
OpenAlex: W2036586619
Cited by: 202
References: 46
Citations by year: 2026: 8 · 2025: 8 · 2024: 16 · 2023: 9 · 2022: 15 · 2021: 12 · 2020: 12 · 2019: 16 · 2018: 11 · 2017: 13 · 2016: 12 · 2015: 5 · 2014: 10 · 2013: 16 · 2012: 11
FWCI: 8.31
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Science Foundation Ireland
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: fractalkine, CX3CR1, microglial activation, phosphatidylinositol 3-kinase pathway, neuroinflammation, lipopolysaccharide, aging, neurodegenerative diseases, IL-1β, microglia-neuron interaction
MeSH terms: Age Factors, Aging, Animals, Animals, Newborn, Cells, Cultured, Enzyme Activation, Lipopolysaccharides, Male, Membrane Proteins, Solubility, Signal Transduction, Rats, Wistar, Microglia, Phosphatidylinositol 3-Kinases, Rats, Chemokine CX3CL1

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Fractalkine‐induced activation of the phosphatidylinositol‐3 kinase pathway attentuates microglial activation in vivo and in vitro

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