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Updated: Jul 30, 2026

Assessing Retinal Microglial Phagocytic Function In Vivo Using a Flow Cytometry-based Assay
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Adrenergic Control of P2Y6 Receptor-Dependent Phagocytosis in Rodent and Human Microglia

Thomas Deluc1,2, Ariel Ase1,2, Marie-France Dorion1

  • 1Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.

Glia
|July 16, 2025
PubMed

Insights

Microglia

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are central nervous system immune cells that respond to neuronal danger signals via purinergic receptors.
  • The P2Y6 receptor on microglia is crucial for phagocytosis, a process often dysregulated in neurodegenerative diseases and chronic pain.
  • Mechanisms modulating P2Y6 receptor activity are not fully understood.

Purpose of the Study:

  • To investigate the modulatory role of the microglial β2 adrenergic receptor (ADRB2) on P2Y6 receptor function.
  • To determine if ADRB2 signaling impacts P2Y6-mediated microglial phagocytosis and gene expression.

Main Methods:

  • Calcium imaging in primary mouse microglia and human iPSC-derived microglia.
  • Pharmacological activation and antagonism of ADRB2.
  • Assessment of microglial phagocytotic activity.
  • Quantitative analysis of P2Y6 mRNA expression.

Main Results:

  • ADRB2 activation by isoproterenol inhibited P2Y6-evoked calcium transients in microglia.
  • This inhibition was reversed by the ADRB2 antagonist ICI-118551 and conserved in human microglia.
  • ADRB2 signaling reduced P2Y6-induced phagocytosis in both mouse and human microglia.
  • ADRB2 activation led to decreased P2Y6 mRNA expression.

Conclusions:

  • ADRB2 signaling functionally and transcriptionally modulates P2Y6 receptor activity in microglia.
  • This crosstalk between adrenergic and purinergic signaling influences microglial responses.
  • These findings offer insights into the pathophysiology of neuro-immune disorders and chronic pain.
Keywords:
calciumchronic painmicroglianorepinephrinephagocytosispurinergic receptors

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