Nonactivated microglia promote oligodendrocyte precursor survival and maturation through the transcription factor NF-kappa B

We demonstrate a role for nonactivated rat microglia in the survival and ma turation of oligodendrocyte precursor cells (OPCs). Media conditioned by no nactivated microglia increase the number of surviving galactocerebroside(+) (GalC(+)) oligodendrocytes in vitro at 48 h by inhibiting the apoptosis of OPCs and stimulating their maturation to GalC(+) oligodendrocytes. These e ffects are not observed with medium conditioned by microglia activated with interferon-gamma (IFN-gamma). Conditioned medium from nonactivated microgl ia is associated with upregulation in OPCs of nuclear factor of kappa bindi ng (NF-kappaB) p65 subunit. The use of antisense to the inhibitor of kappa binding (I kappaB) induces p65 subunit activation in OPCs and, in common wi th medium conditioned by nonactivated microglia, also inhibits OPC apoptosi s and promotes cell maturation. Anti-platelet-derived growth factor (PDGF) antibody abolishes this effect even though PDGF-A chain is expressed at sim ilar levels within both nonactivated and IFN-gamma -activated microglia and both conditioned media have similar levels of PDGF-A chain bioactivity. Ho wever, only conditioned medium from nonactivated microglia recruit phosphat idyl-3-inositol (PI-3) kinase to the PDGF-alpha receptor and synergise with endogenous PDGF-A chain to increase NF-kappaB activation. These results su ggest that, dependent on their state of activation, microglia produce solub le factors that promote oligodendrocyte development through an effect on th e PDGF-alpha receptor-signalling pathway.