Zinc-aggravated M1 microglia suppress astrocytic engulfing activity via P2X7 receptors

Abstract

[AIM] Extracellular zinc aggravates microglial M1 phenotype. Here, we investigated whether zinc-aggravated M1 microglia affects the astrocytic engulfing activity.

[METHODS] Mouse astrocytes were incubated with microglial-conditioned medium (MCM) collected from M1 microglia induced by lipopolysaccharide (LPS) after ZnCl₂ treatment. Astrocytic engulfment activity was examined by beads uptake assay. The mRNA level of P2X7 receptors (P2X7R) in astrocytes was measured by real-time PCR. Effect of A43809, a P2X7R antagonist, on MCM-induced astrocytic engulfment was also examined.

[RESULTS] MCM from M1 microglia increased the bead uptake by astrocytes. This increased engulfment activity was suppressed when astrocytes were treated with MCM from LPS-induced M1 microglia pretreated with ZnCl₂. P2X7R mRNA level was increased in astrocytes treated with MCM from M1 microglia, but not from M1 microglia pretreated with ZnCl₂. Treatment of astrocytes with A438079 resulted in attenuation of increase in the engulfment activity in astrocytes after MCM treatment.

[CONCLUSION] These results suggest zinc pretreatment abolishes the ability of M1 microglia to increase the engulfing activity in astrocytes via alteration of astrocytic P2X7R.