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Updated: Apr 15, 2026
Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
Published on: January 31, 2019
Different danger signals differently impact on microglial proliferation through alterations of ATP release and
Jimmy George1, Francisco Q Gonçalves1, Gonçalo Cristóvão1
1CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
Abstract:
Microglia rely on their ability to proliferate in the brain parenchyma to sustain brain innate immunity and participate in the reaction to brain damage. We now studied the influence of different danger signals activating microglia, both internal (typified by glutamate, associated with brain damage) and external (using a bacterial lipopolysaccharide, LPS), on the proliferation of microglia cells. We found that LPS (100 ng/mL) increased, whereas glutamate (0.5 mM) decreased proliferation. Notably, LPS decreased whereas glutamate increased the extracellular levels of ATP. In contrast, LPS increased whereas glutamate decreased the extracellular catabolism of ATP into adenosine through ecto-nucleotidases and ecto-5'-nucleotidase. Finally, apyrase (degrades extracellular ATP) abrogated glutamate-induced inhibition of microglia proliferation; conversely, inhibitors of ecto-nucleotidases (ARL67156 or α,β-methylene ADP) and adenosine deaminase (degrades extracellular adenosine) abrogated the LPS-induced increase of microglia proliferation, which was blocked by a selective A2A receptor antagonist, SCH58261 (50 nM). Overall, these results highlight the importance of the extracellular purinergic metabolism to format microglia proliferation and influence the spatio-temporal profile of neuroinflammation in different conditions of brain damage.
Insights
Bacterial lipopolysaccharide (LPS) boosts microglia proliferation, while glutamate inhibits it, by altering extracellular ATP and adenosine levels. Purinergic metabolism critically regulates microglia
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are essential for brain immunity and repair after injury.
- Microglia proliferation is crucial for responding to brain damage.
- Understanding signals that control microglia is key for neuroinflammation research.
Purpose of the Study:
- To investigate how different danger signals influence microglia proliferation.
- To explore the role of extracellular purinergic metabolism in microglia responses.
- To differentiate the effects of internal (glutamate) and external (LPS) signals.
Main Methods:
- Cultured microglia cells were exposed to LPS and glutamate.
- Extracellular ATP and adenosine levels were measured.
- Enzyme activity (ecto-nucleotidases, adenosine deaminase) and receptor activity were assessed.
- Proliferation was quantified following various treatments.
Main Results:
- LPS (100 ng/mL) increased microglia proliferation; glutamate (0.5 mM) decreased it.
- LPS decreased extracellular ATP and increased adenosine; glutamate had opposite effects.
- Apyrase blocked glutamate's inhibitory effect on proliferation.
- Inhibitors of ecto-nucleotidases and adenosine deaminase, plus an A2A receptor antagonist, blocked LPS-induced proliferation.
Conclusions:
- Extracellular purinergic metabolism significantly shapes microglia proliferation.
- Different danger signals modulate microglia responses via distinct purinergic pathways.
- These findings offer insights into neuroinflammation regulation in brain damage contexts.
