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P2Y12 Receptor Function Governs Microglial Surveillance and Cell-Cell Interactions in the Cerebral Cortex.

Balázs Pósfai¹, Eszter Szabadits¹, Csaba Cserép¹

¹Momentum Laboratory of Neuroimmunology, HUN-REN Institute of Experimental Medicine, Budapest, Hungary.

|December 2, 2025

Summary

The P2Y12 receptor (P2Y12R) is crucial for microglial surveillance and cell interactions in the brain. Its dysfunction impacts neurological states by altering microglial physiology and communication.

Keywords:

clustering direct contact epilepsy homeostasis in vivo imaging microglial physiology morphology

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Published on: April 13, 2017

Area of Science:

Neuroscience
Cell Biology
Neuroimmunology

Background:

Microglia are key immune cells in the central nervous system, sensing damage and maintaining homeostasis.
Purinergic signaling via the P2Y12 receptor (P2Y12R) is vital for microglial process movement in response to ATP.
P2Y12R influences microglial interactions with neurovascular elements and outcomes in brain injury models.

Purpose of the Study:

To resolve discrepancies between ex vivo and in vivo observations regarding P2Y12R's role in microglial physiology.
To investigate the precise function of P2Y12R in shaping microglial phenotypes and interactions under physiological conditions.

Main Methods:

In vivo 3D two-photon imaging and high-resolution anatomy in mice.
Genetic deletion and acute pharmacological blockade of P2Y12R.
Molecular anatomy of P2Y12R expression analysis.

Main Results:

P2Y12Rs are essential regulators of homeostatic microglial surveillance and cell contacts.
P2Y12R dysfunction alters microglial morphology, surveillance, and nanoclustering.
Changes in microglial contacts with neurons, blood vessels, and oligodendrocytes were observed.
P2Y12R expression correlates with disease severity and altered microglia-neuron interactions in human epilepsy.

Conclusions:

P2Y12Rs are critical for microglial physiology and surveillance in the brain.
Dysfunction of P2Y12Rs significantly impacts cell-cell interactions in neurological conditions.
P2Y12R emerges as a key player in maintaining microglial function and interactions in health and disease.