Microglial phagocytosis dysfunction in the dentate gyrus is related to local neuronal activity in a genetic model of epilepsy Article Swipe
Virginia Sierra‐Torre
,
Ainhoa Plaza‐Zabala
,
P. Bonifazi
,
Oihane Abiega
,
Irune Díaz‐Aparicio
,
Saara Tegelberg
,
Anna‐Elina Lehesjoki
,
Jorge Valero
,
Amanda Sierra
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1111/epi.16692
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1111/epi.16692
Objective Microglial phagocytosis of apoptotic cells is an essential component of the brain regenerative response during neurodegeneration. Whereas it is very efficient in physiological conditions, it is impaired in mouse and human mesial temporal lobe epilepsy, and now we extend our studies to a model of progressive myoclonus epilepsy type 1 in mice lacking cystatin B (CSTB). Methods We used confocal imaging and stereology‐based quantification of apoptosis and phagocytosis of the hippocampus of Cstb knockout (KO) mice, an in vitro model of phagocytosis and siRNAs to acutely reduce Cstb expression, and a virtual three‐dimensional (3D) model to analyze the physical relationship between apoptosis, phagocytosis, and active hippocampal neurons. Results Microglial phagocytosis was impaired in the hippocampus of Cstb KO mice at 1 month of age, when seizures arise and hippocampal atrophy begins. This impairment was not related to the lack of Cstb in microglia alone, as shown by in vitro experiments with microglial Cstb depletion. The phagocytosis impairment was also unrelated to seizures, as it was also present in Cstb KO mice at postnatal day 14, before seizures begin. Importantly, phagocytosis impairment was restricted to the granule cell layer and spared the subgranular zone, where there are no active neurons. Furthermore, apoptotic cells (both phagocytosed and not phagocytosed) in Cstb ‐deficient mice were at close proximity to active cFos + neurons, and a virtual 3D model demonstrated that the physical relationship between apoptotic cells and cFos + neurons was specific for Cstb KO mice. Significance These results suggest a complex crosstalk between apoptosis, phagocytosis, and neuronal activity, hinting that local neuronal activity could be related to phagocytosis dysfunction in Cstb KO mice. Overall, these data suggest that phagocytosis impairment is an early feature of hippocampal damage in epilepsy and opens novel therapeutic approaches for epileptic patients based on targeting microglial phagocytosis.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1111/epi.16692
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/epi.16692
- OA Status
- hybrid
- Cited By
- 21
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3087073735
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3087073735Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1111/epi.16692Digital Object Identifier
- Title
-
Microglial phagocytosis dysfunction in the dentate gyrus is related to local neuronal activity in a genetic model of epilepsyWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-09-17Full publication date if available
- Authors
-
Virginia Sierra‐Torre, Ainhoa Plaza‐Zabala, P. Bonifazi, Oihane Abiega, Irune Díaz‐Aparicio, Saara Tegelberg, Anna‐Elina Lehesjoki, Jorge Valero, Amanda SierraList of authors in order
- Landing page
-
https://doi.org/10.1111/epi.16692Publisher landing page
- PDF URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/epi.16692Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/epi.16692Direct OA link when available
- Concepts
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Phagocytosis, Neurodegeneration, Biology, Hippocampal formation, Microglia, Neuroscience, Dentate gyrus, Epilepsy, Apoptosis, Subiculum, Cell biology, Immunology, Pathology, Medicine, Inflammation, Biochemistry, DiseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
21Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 5, 2024: 6, 2023: 5, 2022: 2, 2021: 3Per-year citation counts (last 5 years)
- References (count)
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53Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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