Changes in phagocytosis and potassium channel activity in microglia of 5xFAD mice indicate alterations in purinergic signaling in a mouse model of Alzheimer’s disease
Abstract
As the immunocompetent cells of the central nervous system, microglia accumulate at amyloid beta plaques in Alzheimer's disease (AD) and acquire a morphological phenotype of activated microglia. Recent functional studies, however, indicate that in mouse models of amyloidosis and AD, these cells are rather dysfunctional indicated by a reduced phagocytic activity. Here, we report that this reduction in phagocytic activity is associated with perturbed purinergic receptor signaling, since phagocytosis could be stimulated by P2Y 6 receptor activation in control, but not in 5xFAD transgenic animals, an animal model of amyloid deposition. Impaired phagocytosis is not innate, and develops only at later stages of amyloidosis. Furthermore, we show that membrane currents induced by uridine diphosphate, a ligand activating P2Y 6 receptors, are altered in response rate and amplitude in microglia in close vicinity to plaques, but not in plaque-free areas of 5xFAD animals. These changes were accompanied by changes in membrane properties and potassium channel activity of plaque-associated microglia in early and late stages of amyloidosis. As a conclusion, the physiological properties of plaque-associated microglia are altered with a strong impact on purinergic signaling.
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Development of outward K+ current in microglia is associated with an advanced microglial activation status.
“Development of outward K+ current in microglia is associated with an advanced microglial activation status (Boucsein et al., 2000; Wendt et al., 2017)”
From Overexpressing low‐density lipoprotein receptor reduces tau‐associated neurodegeneration in relation to apoE‐linked mechanisms (2021) · cites this paper as Wendt et al., 2017
Cites
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Transcriptional and Translational Differences of Microglia from Male and Female Brains
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- Authors
- Wendt, S., Maricos, M., Vana, N., Meyer, N., Guneykaya, D., Semtner, M., & Kettenmann, H.
- Affiliations
- Max Delbrück Center (DE)
- Corresponding author
- Kettenmann, Helmut
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 58
- Pages
- 41-53
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2621707445
- Cited by
- 69
- References
- 10
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 19 · 2020: 11 · 2019: 6 · 2018: 8 · 2017: 1 · 2013: 1
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (EXC 257 NeuroCure, SFB TRR43)
- 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 › Physiology › Adenosine and Purinergic Signaling
- Keywords
- microglia, phagocytosis, purinergic signaling, P2Y6 receptor, potassium channels, 5xFAD mice, Alzheimer's disease, amyloid plaques, amyloidosis, uridine diphosphate, membrane currents, microglial dysfunction
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Phagocytosis, Receptors, Purinergic, Potassium Channels, Signal Transduction, Amyloid beta-Peptides, Microglia, Plaque, Amyloid
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