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Astrocytes Regulate Microglial Phagocytosis of Senile Plaque Cores of Alzheimer's Disease
Abstract
We have developed an in vitro model in which isolated senile plaque (SP) cores are presented to rat microglial cells in culture. Microglia rapidly phagocytosed, broke apart, and cleared SP cores. However, when cocultured with astrocytes, microglial phagocytosis was markedly suppressed, allowing the SPs to persist. Suppression of phagocytosis by astrocytes appears to be a general phenomena since microglia in the presence of astrocytes showed reduced capacity to phagocytose latex beads as well. The astrocyte effect on microglia is related in part to a diffusible factor(s) since astrocyte- but not fibroblast-conditioned media also reduced phagocytosis. These results suggest that while microglia have the capacity to phagocytose and remove SPs, astrocytes which lie in close association to microglia may help prevent the efficient clearance of SP material allowing them to persist in Alzheimer's disease.
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“Moreover, astrocytes can also modulate microglial responses to Aβ [55, 58, 59].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [59]
Citations
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Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
Games, D., Adams, D., Alessandrini, R., Barbour, R., Borthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., et al. (1995) · Nature · doi:10.1038/373523a0 · Cited by 2,516
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Itagaki, S., McGeer, P. L., Akiyama, H., Zhu, S., & Selkoe, D. (1989) · Journal of Neuroimmunology · doi:10.1016/0165-5728(89)90115-x · Cited by 940
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Cai, X.-D., Golde, T. E., & Younkin, S. G. (1993) · Science · doi:10.1126/science.8424174 · Cited by 913
McGeer, P. L., Itagaki, S., Tago, H., & McGeer, E. G. (1987) · Neuroscience Letters · doi:10.1016/0304-3940(87)90696-3 · Cited by 836
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Sorted by citations
Inflammation and Alzheimer’s disease
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Reactive Astrocytes Protect Tissue and Preserve Function after Spinal Cord Injury
Faulkner, J. R., Herrmann, J. E., Woo, M. J., Tansey, K. E., Doan, N., & Sofroniew, M. V. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3547-03.2004 · Cited by 1,652
“These findings agree with studies showing that astrocytes suppress the phagocytic capacity of microglia in vitro (DeWitt et al., 1998).”
ResultInflammation in Neurodegenerative Disease—A Double-Edged Sword
Wyss-Coray, T., & Mucke, L. (2002) · Neuron · doi:10.1016/s0896-6273(02)00794-8 · Cited by 1,235
Interleukin-6, a Major Cytokine in the Central Nervous System
Erta, M., Quintana, A., & Hidalgo, J. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.4679 · Cited by 1,093
“Astrocytes also may be involved in the clearance of beta-amyloid peptide [187], also by regulating microglial phagocytosis [188].”
BackgroundAdult mouse astrocytes degrade amyloid-β in vitro and in situ
Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anankov, R., Yan, F., Silverstein, S. C., & Husemann, J. (2003) · Nature Medicine · doi:10.1038/nm838 · Cited by 909
Metadata
- Authors
- DeWitt, D. A., Perry, G., Cohen, M., Doller, C., & Silver, J.
- Affiliations
- Case Western Reserve University (US)
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 1998-02
- Volume
- 149
- Issue
- 2
- Pages
- 329-340
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2164956116
- Cited by
- 261
- References
- 69
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 11 · 2022: 6 · 2021: 12 · 2020: 3 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 12 · 2015: 13 · 2014: 11 · 2013: 8 · 2012: 13
- FWCI
- 6.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Scholars Crossing (Liberty University) (submittedVersion)
- Funders
- National Institutes of Health (5r01ag009287-08)
- National Institute on Aging (AG-00105-11A1, T32AG000105, AG 09287)
- National Institute of Neurological Disorders and Stroke (NS 25713)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- astrocytes, microglia, phagocytosis, amyloid plaques, Alzheimer's disease, plaque clearance, astrocyte-microglia interaction, conditioned medium, diffusible factors, latex bead phagocytosis, fibroblasts
- MeSH terms
- Alzheimer Disease, Animals, Animals, Newborn, Astrocytes, Brain, Cells, Cultured, Cerebral Cortex, Frontal Lobe, Humans, Phagocytosis, Temporal Lobe, Rats, Sprague-Dawley, Microglia, Coculture Techniques, Rats, Plaque, Amyloid
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