The adenosine generating enzymes CD39/CD73 control microglial processes ramification in the mouse brain

摘要: Microglial cells invade the brain as amoeboid precursors and acquire a highly ramified morphology in postnatal brain. Microglia express all essential purinergic elements such receptors, nucleoside transporters ecto-enzymes, including CD39 (NTPDase1) CD73 (5'-nucleotidase), which sequentially degrade extracellular ATP to adenosine. Here, we show that constitutive deletion of or both caused an inhibition microglia phenotype with reduction length processes, branching frequency number intersections Sholl spheres. In vitro, unlike wild-type microglia, cd39-/- cd73-/- microglial were less complex did not respond transformation into more phenotype. acute slices, retracted approximately 50% their processes within 15 min after slicing brain, this phenomenon was augmented mice; moreover, elongation towards source laser lesion observed only but microglia. An elevation adenosine 1) by transport dipyridamole, 2) application exogenous 3) degradation endogenous ATP/ADP apyrase enhanced spontaneous ATP-induced ramification slices facilitated process-bearing vitro. These data indicate under normal physiological conditions, nucleotidases together equilibrative transporter 1 (ENT1) control fate thereby processes.