Live Imaging of Neuronal Degradation by Microglia Reveals a Role for v0-ATPase a1 in Phagosomal Fusion In Vivo
Open accessAbstract
A significant proportion of neurons in the brain undergo programmed cell death. In order to prevent the diffusion of damaging degradation products, dying neurons are quickly digested by microglia. Despite the importance of microglia in several neuronal pathologies, the mechanism underlying their degradation of neurons remains elusive. Here, we exploit a microglial population in the zebrafish to study this process in intact living brains. In vivo imaging reveals that digestion of neurons occurs in compartments arising from the progressive fusion of vesicles. We demonstrate that this fusion is mediated by the v0-ATPase a1 subunit. By applying live pH indicators, we show that the a1 subunit mediates fusion between phagosomes and lysosomes during phagocytosis, a function that is independent of its proton pump activity. As a real-time description of microglial phagocytosis in vivo, this work advances our understanding of microglial-mediated neuronal degeneration, a hallmark of many neuronal diseases.
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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 [8]
The Introduction and the section on in vivo imaging of zebrafish embryos support that microglia engulf and digest apoptotic neurons. The paper does not establish the claim for AD or PD brains, or show that astrocytes and microglia phagocytose aggregated proteins or secrete cytokines and inflammatory mediators in those conditions. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMicroglia and astrocytes are responsible for many inflammatory processes in affected brains, including phagocytosis of αSYN and Aβ aggregates, secretion of inflammatory mediators, and stimulation of the innate immune system.
“Microglia and astrocytes are known to be responsible for many inflammatory processes in affected brains, including phagocytosis of αSYN and Aβ aggregates, secretion of inflammatory mediators, and stimulation of the innate immune system [8–12].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [8]
The Introduction and the section on neuronal–microglial interactions during brain development describe microglia as CNS immune cells that phagocytose apoptotic neurons, primarily in developing zebrafish brains. They do not establish that microglia or astrocytes phagocytose αSYN or Aβ aggregates in affected brains, secrete inflammatory mediators, or stimulate the innate immune system. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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- Authors
- Peri, F., & Nüsslein-Volhard, C.
- Affiliations
- Max Planck Institute for Developmental Biology (DE)
- Corresponding author
- Peri, Francesca
- ORCID
- Peri, Francesca
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 133
- Issue
- 5
- Pages
- 916-927
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2151844149
- Cited by
- 617
- References
- 3
- Citations by year
- 2026: 25 · 2025: 42 · 2024: 42 · 2023: 30 · 2022: 40 · 2021: 59 · 2020: 30 · 2019: 40 · 2018: 37 · 2017: 33 · 2016: 32 · 2015: 35 · 2014: 38 · 2013: 27 · 2012: 31
- FWCI
- 16.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1903 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Ernst Schering Foundation
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- microglia, phagosome-lysosome fusion, zebrafish, live imaging, proton translocation, lysosomal pH
- MeSH terms
- Animals, Brain, Embryo, Nonmammalian, Neurons, Phagocytosis, Phagosomes, Zebrafish, Apoptosis, Microglia, Vacuolar Proton-Translocating ATPases, Zebrafish Proteins, Animals, Genetically Modified
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