Cited by 234Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchNeurological Disease Mechanisms and Treatments

Microglial CR3 Activation Triggers Long-Term Synaptic Depression in the Hippocampus via NADPH Oxidase

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Zhang, Jingfei, Malik, Aqsa, Choi, Hyun B., Ko, Rebecca W.Y., Dissing-Olesen, Lasse, MacVicar, Brian A.·2014·Neuron

Abstract

Complement receptor 3 (CR3) activation in microglia is involved in neuroinflammation-related brain disorders and pruning of neuronal synapses. Hypoxia, often observed together with neuroinflammation in brain trauma, stroke, and neurodegenerative diseases, is thought to exacerbate inflammatory responses and synergistically enhance brain damage. Here we show that when hypoxia and an inflammatory stimulus (lipopolysaccharide [LPS]) are combined, they act synergistically to trigger long-term synaptic depression (LTD) that requires microglial CR3, activation of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), and GluA2-mediated A-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization. Microglial CR3-triggered LTD is independent of N-methyl-D-aspartate receptors (NMDARs), metabotropic glutamate receptors (mGluRs), or patterned synaptic activity. This type of LTD may contribute to memory impairments and synaptic disruptions in neuroinflammation-related brain disorders.

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Crossref · 10.1016/j.neuron.2014.01.043

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Authors
Zhang, J., Malik, A., Choi, H. B., Ko, R. W. Y., Dissing-Olesen, L., & MacVicar, B. A.
Affiliations
University of British Columbia (CA)
Corresponding author
MacVicar, Brian A.
Venue
Neuron
Publisher
Elsevier BV
Published
2014-04
Volume
82
Issue
1
Pages
195-207
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2104274085
Cited by
234
References
54
Citations by year
2026: 4 · 2025: 12 · 2024: 11 · 2023: 20 · 2022: 19 · 2021: 30 · 2020: 21 · 2019: 25 · 2018: 14 · 2017: 21 · 2016: 23 · 2015: 20 · 2014: 14
FWCI
13.50
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research (10677)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
microglia, complement receptor 3, NADPH oxidase, long-term depression, hypoxia, lipopolysaccharide, neuroinflammation, AMPA receptor internalization, GluA2, hippocampus, synaptic plasticity, memory impairment
MeSH terms
Acetophenones, Animals, Animals, Newborn, Hypoxia, Enzyme Inhibitors, Hippocampus, L-Lactate Dehydrogenase, Oxygen, Lipid Peroxidation, Macrophage-1 Antigen, Rats, Sprague-Dawley, Microglia, Mice, Knockout, Excitatory Amino Acid Antagonists, NADPH Oxidases, Long-Term Synaptic Depression, CD11b Antigen, Mice, Rats, In Vitro Techniques

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