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

ABSTRACT: Microglial calcium signaling is rare in a baseline state but shows strong engagement during early epilepsy development. The mechanism and purpose behind microglial calcium signaling is not known. By developing an in vivo UDP fluorescent sensor, GRAB_UDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP signals to the microglial P2Y₆ receptor for broad increases in calcium signaling during epileptogenesis. UDP-P2Y₆ signaling is necessary for lysosome upregulation across limbic brain regions and enhances production of pro-inflammatory cytokines-TNFα and IL-1β. Failures in lysosome upregulation, observed in P2Y₆ KO mice, can also be phenocopied by attenuating microglial calcium

SUBMITTER: Umpierre AD 

PROVIDER: S-EPMC10312639 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature