主催: 第94回日本薬理学会年会
会議名: 第94回日本薬理学会年会
回次: 94
開催地: Sapporo
開催日: 2021/03/08 - 2021/03/10
[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.