Microglial CR3 Activation Triggers Long-Term Synaptic Depression in the Hippocampus via NADPH Oxidase
Open accessAbstract
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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Microglia can promote LTD via NADPH oxidase.
“and promote LTD via NADPH oxidase55”
From Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex (2016) · cites this paper as [55]
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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
- bronze
- doi.org
- Licence
- 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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