Cited by 108Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

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Astrocyte‐released cytokines induce ramification and outward K+ channel expression in microglia via distinct signalling pathways

Schilling, Tom, Nitsch, Robert, Heinemann, Uwe, Haas, Dorit, Eder, Claudia·2001·European Journal of Neuroscience

DOI 10.1046/j.0953-816x.2001.01661.x

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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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The Role of α5GABA(A) Receptors in Brain Inflammation
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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
ORCID: Schilling, Tom
Nitsch, Robert
Venue: European Journal of Neuroscience
Publisher: Wiley
Published: 2001-08
Volume: 14
Issue: 3
Pages: 463-473
ISSN: 0953-816X (ISSN-L)
1460-9568
DOI: 10.1046/j.0953-816x.2001.01661.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 141 d)
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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Astrocyte‐released cytokines induce ramification and outward K+ channel expression in microglia via distinct signalling pathways

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