Astrocyte‐released cytokines induce ramification and outward K+ channel expression in microglia via distinct signalling pathways
Abstract
Differentiation of microglial cells is characterized by transformation from ameboid into ramified cell shape and up-regulation of K+ channels. The processes of microglial differentiation are controlled by astrocytic factors. The mechanisms by which astrocytes cause developmental changes in morphological and electrophysiological properties of microglia have remained unclear. We show here that the cytokines transforming growth factor-beta (TGF-beta), macrophage colony-stimulating factor (M-CSF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) are released by astrocytes at concentrations sufficient to induce ramification and up-regulation of delayed rectifier (DR) K+ channels in microglia. Transformation from ameboid into ramified morphology induced in microglia by exposure to astrocyte-conditioned medium (ACM) was inhibited by neutralizing antibodies against TGF-beta, M-CSF or GM-CSF, whilst ACM-induced DR channel expression was exclusively inhibited by antibodies against TGF-beta. Although both ramification and DR channel up-regulation occurred simultaneously, DR channel blockade by charybdotoxin failed to inhibit microglial ramification. The ACM-induced ramification of microglia was inhibited by the tyrosine kinase inhibitor genistein, whereas DR channel up-regulation did not occur in the presence of the serine/threonine kinase inhibitor H7. Our data suggest that astrocytes modulate processes of microglial differentiation in parallel but via distinct signalling pathways.
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Others have reported that in vitro, TGF-β1 signaling induces a quiescent microglial phenotype and promotes resting microglial properties.
“others have reported that in vitro, TGF-β1 signaling induces a quiescent microglial phenotype25 and promotes resting microglial properties26”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [26]
TGFβ is needed for murine microglia development in vivo and for maintaining the microglial-specific transcriptome signature.
“TGFβ, a glia-derived cytokine, is needed for murine microglia development in vivo and in maintaining the microglial-specific transcriptome signature (Abutbul et al., 2012; Butovsky et al., 2014; Schilling et al., 2001).”
From iPSC-derived human microglia-like cells to study neurological diseases (2017) · cites this paper as Schilling et al., 2001
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- Authors
- Schilling, T., Nitsch, R., Heinemann, U., Haas, D., & Eder, C.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Corresponding author
- Eder, Claudia
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2001-08
- Volume
- 14
- Issue
- 3
- Pages
- 463-473
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2093298450
- Cited by
- 108
- References
- 49
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 9 · 2019: 3 · 2018: 5 · 2017: 8 · 2016: 5 · 2015: 2 · 2014: 6 · 2013: 4 · 2012: 2
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- microglial differentiation, astrocytes, cytokines, TGF-beta, macrophage colony-stimulating factor, GM-CSF, delayed rectifier potassium channel, microglial ramification, astrocyte-conditioned medium, genistein, H7, charybdotoxin, signaling pathways
- MeSH terms
- Animals, Astrocytes, Cell Differentiation, Cells, Cultured, Electrophysiology, Membranes, Potassium Channels, Signal Transduction, Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, Transforming Growth Factor beta, Microglia, Patch-Clamp Techniques, Potassium Channels, Voltage-Gated, Mice, Delayed Rectifier Potassium Channels
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