Reactive oxygen species alter dopaminergic and purinergic signaling and microglia physiology in the nucleus accumbens

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Updated: May 19, 2026

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
09:12

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Published on: January 30, 2014

H A Wadsworth, L H Ford, L R Hawley

    Biorxiv : the Preprint Server for Biology
    |May 18, 2026
    PubMed

    Insights

    Microglia in the brain respond to adenosine triphosphate (ATP) more readily than dopamine (DA). Immune activation by lipopolysaccharide (LPS) alters microglia and increases DA and ATP release.

    Area of Science:

    • Neuroimmunology
    • Cellular Neuroscience
    • Neuropharmacology

    Background:

    • Microglia, the brain's immune cells, exhibit complex signaling and phagocytic behaviors.
    • Adenosine triphosphate (ATP) acts as a chemoattractant for microglia.
    • In the nucleus accumbens (NAc), ATP is co-released with dopamine (DA), and microglia possess receptors for both.

    Purpose of the Study:

    • To investigate microglia chemotactic motility towards dopamine (DA) and adenosine triphosphate (ATP) in the NAc.
    • To examine the impact of reactive oxygen species (ROS) and immune activation on microglia and neurotransmitter release.

    Main Methods:

    • Utilized iontophoresis and multiphoton microscopy in NAc brain slices from GFP-monocyte labeled transgenic mice.
    • Administered glucose oxidase to induce reactive oxygen species (ROS) and lipopolysaccharide (LPS) as a toll-like receptor 4 (TLR4) agonist.
    • Assessed microglia morphology, motility, and neurotransmitter release (DA and ATP).

    Main Results:

    • ATP more consistently attracted microglia than DA; DA attraction was observed in a small subset and blocked by D1 antagonism.
    • Glucose oxidase increased ROS, altered microglial morphology/motility, decreased DA release, and had variable effects on ATP release.
    • LPS induced a transition from ramified to amoeboid microglia morphology and increased both DA and ATP release over 4 hours.

    Conclusions:

    • Microglia exhibit differential chemotactic responses to ATP and DA in the NAc.
    • Immune activation, mediated by ROS or LPS, significantly impacts microglial behavior and neurotransmitter dynamics.
    • These findings underscore the intricate interplay between neuroinflammation and dopaminergic terminal function.

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