The DOI matches its Crossref record; 80 of the 82 references it cites were found in a registry or an index.
Microglia Promote the Death of Developing Purkinje Cells
Open accessAbstract
The loss of neuronal cells, a prominent event in the development of the nervous system, involves regulated triggering of programmed cell death, followed by efficient removal of cell corpses. Professional phagocytes, such as microglia, contribute to the elimination of dead cells. Here we provide evidence that, in addition to their phagocytic activity, microglia promote the death of developing neurons engaged in synaptogenesis. In the developing mouse cerebellum, Purkinje cells die, and 60% of these neurons that already expressed activated caspase-3 were engulfed or contacted by spreading processes emitted by microglial cells. Apoptosis of Purkinje cells in cerebellar slices was strongly reduced by selective elimination of microglia. Superoxide ions produced by microglial respiratory bursts played a major role in this Purkinje cell death. Our study illustrates a mammalian form of engulfment-promoted cell death that links the execution of neuron death to the scavenging of dead cells.
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“In the AD and PD brain, both astrocytes and microglia acquire reactive, inflammatory phenotypes and can effectively phagocytose aggregated proteins and cell debris, as well as secrete various cytokines and inflammatory mediators [8–13].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [13]
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“Microglia also contribute to the maintenance of brain homeostasis by clearing apoptotic cells in the brain via efferocytosis (27–29).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [27]
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Citations
Cites
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Porter, A. G., & Jänicke, R. U. (1999) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400476 · Cited by 3,921
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Apoptosis in the nervous system
Yuan, J., & Yankner, B. A. (2000) · Nature · doi:10.1038/35037739 · Cited by 1,882
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Sorted by citations
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110
Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547
Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor
Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., Lafaille, J. J., Hempstead, B. L., Littman, D. R., & Gan, W.-B. (2013) · Cell · doi:10.1016/j.cell.2013.11.030 · Cited by 2,599
Metadata
- Authors
- Marı́n-Teva, J. L., Dusart, I., Colin, C., Gervais, A., van Rooijen, N., & Mallat, M.
- Affiliations
- Inserm (FR)
- Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Mallat, Michel
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 41
- Issue
- 4
- Pages
- 535-547
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2103711259
- Cited by
- 757
- References
- 82
- Citations by year
- 2026: 13 · 2025: 38 · 2024: 35 · 2023: 45 · 2022: 45 · 2021: 50 · 2020: 30 · 2019: 47 · 2018: 39 · 2017: 29 · 2016: 42 · 2015: 38 · 2014: 42 · 2013: 40 · 2012: 40
- FWCI
- 17.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- HAL (submittedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- 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, Purkinje cells, neuronal apoptosis, cerebellar development, phagocytosis, caspase-3, superoxide, synaptogenesis, neuronal cell death
- MeSH terms
- Animals, Antibodies, Cell Communication, Cell Differentiation, Cell Survival, Cerebellar Cortex, Enzyme Inhibitors, Mice, Inbred C57BL, Purkinje Cells, Signal Transduction, Free Radical Scavengers, Apoptosis, Microglia, Presynaptic Terminals, Receptors, Tumor Necrosis Factor, Mice, Knockout, Cell Respiration, Caspases, Mice, Caspase 3, In Vitro Techniques
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