β-Amyloid Stimulates Murine Postnatal and Adult Microglia Cultures in a Unique Manner
Open accessAbstract
Reactive microglia are commonly observed in association with the β-amyloid (Aβ) plaques of Alzheimer's disease brains. This localization supports the hypothesis that Aβ is a specific activating stimulus for microglia. A variety of in vitro studies have used postnatal derived rodent microglia cultures to characterize the ability of Aβ to stimulate these cells. However, it is unclear whether this paradigm accurately models conditions in aged animals. To determine whether Aβ stimulatory phenotypes differ between young and adult microglia, we established cultures of acutely isolated adult murine cortical microglia to compare with postnatal derived microglial cultures. Although cells from both ages expressed robust immunoreactivity for CD68 and CD11b, their responses to activating stimuli differed. Fibrillar Aβ was rapidly phagocytosed by postnatal microglia and both oligomeric and fibrillar peptide stimulated increased tumor necrosis factor α (TNFα) secretion. However, Aβ oligomers but not fibrils stimulated TNFα secretion from adult microglia. More importantly, adult microglia had diminished ability to phagocytose Aβ fibrils. These findings demonstrate that adult microglia respond to Aβ fibril stimulation uniquely from postnatal cells and suggest that adult rather than postnatal microglia cultures are more appropriate for modeling proinflammatory changes in the aged CNS.
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Phagocytosis of aged FAM-labeled Aβ1-42 by microglia in vitro was controlled by laser confocal microscopy and immunoprecipitation of Aβ in lysates of microglial cells.
“Phagocytosis of aged FAM-labeled A1-42 by microglia in vitro was assayed as previously described by Floden and Combs (2006), and controlled by laser confocal microscopy and immunoprecipitation of A in lysates of microglial cells.”
From Critical Role of Astroglial Apolipoprotein E and Liver X Receptor-α Expression for Microglial Aβ Phagocytosis (2011) · cites this paper as Floden and Combs (2006)
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- Authors
- Floden, A. M., & Combs, C. K.
- Affiliations
- University of North Dakota (US)
- ORCID
- Combs, Colin K.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-04-26
- Volume
- 26
- Issue
- 17
- Pages
- 4644-4648
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674057
- OpenAlex
- W1982506852
- Cited by
- 118
- References
- 5
- Citations by year
- 2023: 2 · 2022: 12 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 6 · 2015: 9 · 2014: 8 · 2013: 11 · 2012: 9
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Center for Research Resources (P20RR17699, 1P20 RR 17699-01, P20RR017699)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- amyloid-beta, microglia, Alzheimer's disease, microglial activation, phagocytosis, amyloid fibrils, amyloid oligomers, TNF-α, CD68, CD11b, aging, cortical microglia
- MeSH terms
- Aging, Animals, Animals, Newborn, Brain, Cell Survival, Cells, Cultured, Dose-Response Relationship, Drug, Mice, Inbred C57BL, Peptide Fragments, Phagocytosis, Tumor Necrosis Factor-alpha, Amyloid beta-Peptides, Microglia, Mice
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