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Updated: Apr 20, 2026

Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Serotonin stimulates secretion of exosomes from microglia cells
Konstantin Glebov1, Marie Löchner, Ronald Jabs
1Department of Neurology, University of Bonn, Bonn, Germany.
Abstract:
Microglia are resident immune cells in the brain and exert important functions in the regulation of inflammatory processes during infection or cellular damage. Upon activation, microglia undergo complex morphological and functional transitions, including increased motility, phagocytosis and cytokine secretion. Recent findings indicate that exosomes, small vesicles that derive from fusion of multivesicular bodies with the plasma membrane, are involved in secretion of certain cytokines. The presence of specific receptors on the surface of microglia suggests communication with neurons by neurotransmitters. Here, we demonstrate expression of serotonin receptors, including 5-HT2a,b and 5-HT4 in microglial cells and their functional involvement in the modulation of exosome release by serotonin. Our data demonstrate the involvement of cAMP and Ca(2+) dependent signaling pathways in the regulation of exosome secretion. Co-culture of microglia with embryonic stem cell-derived serotonergic neurons further demonstrated functional signaling between neurons and microglia. Together, these data provide evidence for neurotransmitter-dependent signaling pathways in microglial cells that regulate exosome release.
Insights
Serotonin receptors on microglia modulate exosome release via cAMP and Ca(2+) signaling pathways. This neurotransmitter-dependent communication between neurons and microglia impacts brain immune cell function.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are brain-resident immune cells crucial for inflammatory responses.
- Activated microglia exhibit changes in motility, phagocytosis, and cytokine secretion.
- Exosomes are implicated in cytokine release, and microglia possess neuronal communication receptors.
Purpose of the Study:
- To investigate the expression and function of serotonin receptors on microglial cells.
- To determine serotonin's role in modulating exosome release from microglia.
- To elucidate the signaling pathways involved in this neurotransmitter-microglia interaction.
Main Methods:
- Demonstration of serotonin receptor (5-HT2a,b, 5-HT4) expression in microglial cells.
- Assessment of serotonin's effect on exosome release.
- Analysis of cAMP and Ca(2+) signaling pathways.
- Co-culture experiments with embryonic stem cell-derived serotonergic neurons.
Main Results:
- Microglial cells express functional serotonin receptors (5-HT2a,b, 5-HT4).
- Serotonin significantly modulates microglial exosome release.
- cAMP and Ca(2+) dependent signaling pathways are involved in this regulation.
- Functional signaling was observed between neurons and microglia in co-culture.
Conclusions:
- Neurotransmitter signaling, specifically via serotonin, influences microglial exosome release.
- This study reveals novel signaling pathways regulating exosome secretion in microglia.
- Establishes a direct link between neuronal activity and microglial immune responses via exosome release.
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