Developmental Neuronal Death in Hippocampus Requires the Microglial CD11b Integrin and DAP12 Immunoreceptor
Open accessAbstract
In several brain regions, microglia actively promote neuronal apoptosis during development. However, molecular actors leading microglia to trigger death remain mostly unknown. Here, we show that, in the developing hippocampus, apoptotic neurons are contacted by microglia expressing both the integrin CD11b and the immunoreceptor DAP12. We demonstrate that developmental apoptosis decreases in mice deficient for CD11b or DAP12. In addition, function-blocking antibodies directed against CD11b decrease neuronal death when injected into wild-type neonates, but have no effect when injected into DAP12-deficient littermates. This demonstrates that DAP12 and CD11b act in converging pathways to induce neuronal death. Finally, we show that DAP12 and CD11b control the production of microglial superoxide ions, which kill the neurons. Thus, our data show that the process of developmental neuronal death triggered by microglia is similar to the elimination of pathogenic cells by the innate immune cells.
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The cytotoxic activity of phagosomal O2− participates in normal development, where engulfing microglia cause neuronal apoptosis.
“The cytotoxic activity of phagosomal O 2 ⅐Ϫ also participates in normal development, where engulfing microglia cause neuronal apoptosis (Marín-Teva et al., 2004;Wakselman et al., 2008).”
From Neurotoxic Activation of Microglia Is Promoted by a Nox1-Dependent NADPH Oxidase (2008) · cites this paper as Wakselman et al., 2008
The Discussion reports that microglial superoxide contributes to neuronal death during hippocampal development, and the Results describe superoxide-producing microglia contacting apoptotic neurons. The paper distinguishes this death-promoting activity from phagocytosis; it does not establish that the superoxide is phagosomal or that the microglia cause apoptosis by engulfing neurons. The indexed passages have no page numbers. (LLM, conf=0.87)
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- Authors
- Wakselman, S., Béchade, C., Roumier, A., Bernard, D., Triller, A., & Bessis, A.
- Affiliations
- Inserm (FR)
- Corresponding author
- Bessis, Alain
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-08-06
- Volume
- 28
- Issue
- 32
- Pages
- 8138-8143
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6670768
- OpenAlex
- W2060061788
- Cited by
- 351
- References
- 5
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 27 · 2023: 25 · 2022: 24 · 2021: 31 · 2020: 18 · 2019: 28 · 2018: 25 · 2017: 26 · 2016: 17 · 2015: 25 · 2014: 25 · 2013: 18 · 2012: 18
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- microglia, neuronal apoptosis, hippocampus, DAP12, superoxide, innate immunity, neuroimmune interactions, neonatal brain development
- MeSH terms
- Animals, Cell Communication, Hippocampus, Immunity, Innate, Mice, Mutant Strains, Neurons, Receptors, Immunologic, Superoxides, Apoptosis, Microglia, Mice, Knockout, CD11b Antigen, Adaptor Proteins, Signal Transducing, Mice
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