Microglial P2Y₆ calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis.

ABSTRACT: Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRAB_UDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y₆ receptor to increase calcium activity during epileptogenesis. P2Y₆ calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y₆ receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through calciu

SUBMITTER: Umpierre AD 

PROVIDER: S-EPMC11189754 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature