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Updated: May 25, 2026
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Microvesicles released from microglia stimulate synaptic activity via enhanced sphingolipid metabolism
Flavia Antonucci1, Elena Turola, Loredana Riganti
1Department of Medical Pharmacology, CNR Institute of Neuroscience, Università di Milano, Milano, Italy.
Abstract:
Microvesicles (MVs) released into the brain microenvironment are emerging as a novel way of cell-to-cell communication. We have recently shown that microglia, the immune cells of the brain, shed MVs upon activation but their possible role in microglia-to-neuron communication has never been explored. To investigate whether MVs affect neurotransmission, we analysed spontaneous release of glutamate in neurons exposed to MVs and found a dose-dependent increase in miniature excitatory postsynaptic current (mEPSC) frequency without changes in mEPSC amplitude. Paired-pulse recording analysis of evoked neurotransmission showed that MVs mainly act at the presynaptic site, by increasing release probability. In line with the enhancement of excitatory transmission in vitro, injection of MVs into the rat visual cortex caused an acute increase in the amplitude of field potentials evoked by visual stimuli. Stimulation of synaptic activity occurred via enhanced sphingolipid metabolism. Indeed, MVs promoted ceramide and sphingosine production in neurons, while the increase of excitatory transmission induced by MVs was prevented by pharmacological or genetic inhibition of sphingosine synthesis. These data identify microglia-derived MVs as a new mechanism by which microglia influence synaptic activity and highlight the involvement of neuronal sphingosine in this microglia-to-neuron signalling pathway.
Insights
Microglia-derived microvesicles (MVs) enhance excitatory neurotransmission in the brain. This effect is mediated by increased sphingolipid metabolism in neurons, revealing a novel communication pathway.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microvesicles (MVs) are key mediators of intercellular communication in the brain.
- Microglia, the brain's immune cells, release MVs upon activation.
- The role of microglia-derived MVs in neuron communication remains unexplored.
Purpose of the Study:
- To investigate the effect of microglia-derived MVs on neuronal neurotransmission.
- To elucidate the underlying molecular mechanisms of this communication.
Main Methods:
- Analysis of spontaneous glutamate release in cultured neurons exposed to MVs.
- Paired-pulse recordings to assess evoked neurotransmission.
- In vivo electrophysiological recordings in rat visual cortex following MV injection.
- Measurement of sphingolipid metabolites (ceramide, sphingosine).
- Pharmacological and genetic inhibition of sphingosine synthesis.
Main Results:
- Microglia-derived MVs dose-dependently increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in neurons.
- MVs enhanced evoked neurotransmission by increasing presynaptic release probability.
- In vivo MV injection increased field potential amplitudes in response to visual stimuli.
- MVs elevated ceramide and sphingosine levels in neurons.
- Inhibition of sphingosine synthesis blocked the excitatory effects of MVs.
Conclusions:
- Microglia-derived MVs represent a novel mechanism for microglia-to-neuron communication.
- Neuronal sphingolipid metabolism, particularly sphingosine synthesis, is crucial for this signaling pathway.
- These findings offer new insights into neuroinflammation and synaptic function.
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