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- W2989872242 abstract "Abstract During Alzheimer’s disease (AD) progression, microglial cells play complex roles and have potentially detrimental as well as beneficial effects. The use of appropriate model systems is essential for characterizing and understanding the roles of microglia in AD pathology. Here, we used organotypic hippocampal slice cultures (OHSCs) to investigate the impact of microglia on amyloid beta (Aβ)‐mediated toxicity. Neurons in OHSCs containing microglia were not vulnerable to cell death after 7 days of repeated treatment with Aβ 1‐42 oligomer‐enriched preparations. However, when clodronate was used to remove microglia, treatment with Aβ 1‐42 resulted in significant neuronal death. Further investigations indicated signs of endoplasmic reticulum stress and caspase activation after Aβ 1‐42 challenge only when microglia were absent. Interestingly, microglia provided protection without displaying any classic signs of activation, such as an amoeboid morphology or the release of pro‐inflammatory mediators (e.g., IL‐6, TNF‐α, NO). Furthermore, depleting microglia or inhibiting microglial uptake mechanisms resulted in significant more Aβ deposition compared to that observed in OHSCs containing functional microglia, suggesting that microglia efficiently cleared Aβ. Because inhibiting microglial uptake increased neuronal cell death, the ability of microglia to engulf Aβ is thought to contribute to its protective properties. Our study argues for a beneficial role of functional ramified microglia whereby they act against the accumulation of neurotoxic forms of Aβ and support neuronal resilience in an in situ model of AD pathology." @default.
- W2989872242 created "2019-12-05" @default.
- W2989872242 creator A5006128286 @default.
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- W2989872242 creator A5036520519 @default.
- W2989872242 creator A5053579288 @default.
- W2989872242 creator A5059104487 @default.
- W2989872242 creator A5064422858 @default.
- W2989872242 date "2020-01-13" @default.
- W2989872242 modified "2023-09-27" @default.
- W2989872242 title "The neuroprotective role of microglial cells against amyloid beta‐mediated toxicity in organotypic hippocampal slice cultures" @default.
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