Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury
Open accessAbstract
Phagocytosis of synaptic material by microglia is critical for central nervous system development. Less well understood is this microglial function in the injured adult brain. Assay of microglial phagocytosis is challenging, because peripheral myeloid cells engraft the site of injury, which could obscure interpretation of microglial roles. The model used here, optic nerve crush injury, results in degeneration of synapses in the dorsal lateral geniculate nucleus (dLGN), which stimulates rapid activation and engulfment of synaptic material by resident microglia without myeloid cell engraftment. Pharmacological depletion of microglia causes postinjury accumulation of synaptic debris, suggesting that microglia are the dominant postinjury phagocytes. Genetic or pharmacological manipulations revealed that neuronal activity does not trigger microglia phagocytosis after injury. RNA sequencing reveals C1q and CD11b/CR3 involvement in clearance of debris by dLGN-resident microglia. Indeed, C1qa−/− and Itgam−/− mice exhibit impaired postinjury debris clearance. Our results show how neurodegenerative debris is cleared by microglia and offers a model for studying its mechanisms and physiological roles.
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Neuron-glia signaling mechanisms also regulate synaptic dysfunction and loss following neural injury or in the context of neurodegenerative disease.
“Neuron-glia signaling mechanisms also regulate synaptic dysfunction and loss following neural injury or in the context of neurodegenerative disease (Hong et al. 2016, Lui et al. 2016, Norris et al. 2018, Schafer et al. 2016, Vasek et al. 2016;reviewed in Salter & Stevens 2017).”
From Neuron-glia signaling in synapse elimination (2019) · cites this paper as Norris et al. 2018
Complement-mediated microglial engulfment plays a role in synaptic elimination following nerve injury.
“In addition to these chronic neurodegenerative paradigms, complement-mediated microglial engulfment also plays a role in synaptic elimination following nerve injury (Norris et al. 2018).”
From Neuron-glia signaling in synapse elimination (2019) · cites this paper as Norris et al. 2018
Following optic nerve crush, microglia are the primary mediators of synaptic clearance at distal targets.
“Following optic nerve crush, microglia are the primary mediators of synaptic clearance at distal targets.”
From Neuron-glia signaling in synapse elimination (2019) · cites this paper as Norris et al. 2018
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References 73 · Cited by 109
- Authors
- Norris, G. T., Smirnov, I., Filiano, A. J., Shadowen, H. M., Cody, K. R., Thompson, J. A., Harris, T. H., Gaultier, A., Overall, C. C., & Kipnis, J.
- Affiliations
- University of Virginia (US)
- Corresponding author
- Kipnis, Jonathan
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2018-06-25
- Volume
- 215
- Issue
- 7
- Pages
- 1789-1801
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC6028515
- OpenAlex
- W2811414271
- Cited by
- 109
- References
- 73
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 13 · 2023: 18 · 2022: 17 · 2021: 20 · 2020: 8 · 2019: 16 · 2018: 5
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (MH096484, NS096967)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- microglia, phagocytosis, central nervous system injury, optic nerve crush, dorsal lateral geniculate nucleus, C1q, CD11b, neurodegeneration, neuronal activity, synaptic integrity
- MeSH terms
- Animals, Central Nervous System, Complement System Proteins, Geniculate Bodies, Mice, Inbred C57BL, Nerve Crush, Nerve Degeneration, Neurons, Optic Nerve, Phagocytosis, Synapses, Microglia, Gene Expression Profiling, CD11b Antigen, Cell Proliferation
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