Neuroprotective function for ramified microglia in hippocampal excitotoxicity
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Background: Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration. Methods: Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA) to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia. Results: Treatment of mouse organotypic hippocampal slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA) induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA. Conclusions: Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.
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Organotypic hippocampal slice cultures undergo key developmental steps similar to in vivo, including synapse maturation.
“Organotypic hippocampal slice cultures are known to undergo key developmental steps similar to those observed in vivo, including synapse maturation28–31, and have been previously used to study ramified microglia function32.”
From Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction (2018) · cites this paper as [32]
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- Authors
- Vinet, J., van Weering, H. R., Heinrich, A., Kälin, R. E., Wegner, A., Brouwer, N., Heppner, F. L., van Rooijen, N., Boddeke, H. W., & Biber, K.
- Affiliations
- University Medical Center Groningen (NL)
- University of Freiburg (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Corresponding author
- Vinet, Jonathan
- Biber, Knut
- Venue
- Journal of Neuroinflammation
- Published
- 2012-01-31
- Volume
- 9
- Issue
- 1
- Pages
- 27-27
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC3292937
- OpenAlex
- W1963696719
- Cited by
- 274
- References
- 70
- Citations by year
- 2026: 11 · 2025: 6 · 2024: 18 · 2023: 16 · 2022: 14 · 2021: 20 · 2020: 22 · 2019: 20 · 2018: 18 · 2017: 28 · 2016: 24 · 2015: 18 · 2014: 24 · 2013: 26 · 2012: 9
- FWCI
- 12.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (SFB TRR 43, NeuroCure EXC257, EXC257, FOR1336, TRR-43)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- ramified microglia, neuroprotection, microglia depletion, organotypic hippocampal slice cultures, CA1 neurons, excitotoxic neurodegeneration
- MeSH terms
- Animals, Clodronic Acid, Dose-Response Relationship, Drug, Glial Fibrillary Acidic Protein, Hippocampus, Mice, Inbred C57BL, Mice, Transgenic, Nerve Degeneration, Neurons, Neurotoxins, Organ Culture Techniques, Phosphopyruvate Hydratase, N-Methylaspartate, Cell Death, Microglia, CD11b Antigen, Mice
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