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Cited by 757Neuroinflammation and Neurodegeneration MechanismsPhagocytosis and Immune RegulationCell death mechanisms and regulation

Microglia Promote the Death of Developing Purkinje Cells

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Marı́n-Teva, José Luis, Dusart, Isabelle, Colin, Catherine, Gervais, Annie, van Rooijen, Nico, Mallat, Michel·2004·Neuron
DOI 10.1016/s0896-6273(04)00069-8
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Abstract

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.

    “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]

    The passage on phagocytic behavior in cerebellar slices reports microglia engulfing dying Purkinje cells and says astroglial cells can occasionally ingest apoptotic cell bodies (page unavailable). It does not establish reactive phenotypes, clearance of aggregated proteins, or cytokine secretion by both cell types in AD or PD brains; the Molecular Mediators section instead examines microglial effects during development. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Microglia clear apoptotic cells via efferocytosis, contributing to brain homeostasis.

    “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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2 of the 82 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. lipopolysaccharide-induced death. Proc. Natl. Acad. Sci. USA 92, 10688-10692.
  2. Yu, L., Quinn, M.T., Cross, A.R., and Dinauer, M.C. (1998). Gp91(phox) is the heme binding subunit of the superoxide-generat- ing NADPH oxidase. Proc. Natl. Acad. Sci. USA 95, 7993-7998.

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Authors
Marı́n-Teva, J. L., Dusart, I., Colin, C., Gervais, A., van Rooijen, N., & Mallat, M.
Affiliations
Inserm (FR)
Corresponding author
Mallat, Michel
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2004-02
Volume
41
Issue
4
Pages
535-547
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/s0896-6273(04)00069-8
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
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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