Polarized microglia do not influence oligodendrocyte lineage cells via astrocytes.

Microglia can adopt different activation patterns, ranging from a pro-inflammatory M1- to an anti-inflammatory M2-like phenotype in which they play crucial roles in various neuroinflammatory diseases. M2-like microglia are described to drive remyelination, whereas detrimental effects have been attributed to M1-like microglia. How polarized microglia might act on oligodendrocyte lineage cells indirectly by influencing astrocytes has not been studied in detail. In this study, conditioned media from polarized murine microglia were used to treat astrocytes and astrocytic gene expression was analyzed by microarray for genes known to influence oligodendrocyte lineage cells. Supernatants of astrocytes previously stimulated with soluble effectors from polarized microglia were used to investigate effects on oligodendrocyte precursor cells (OPC). Growth factors known to induce OPC proliferation, differentiation, and survival were upregulated in astrocytes treated with supernatants from M1-like microglia while M0- and M2-like microglia only had negligible effects on the expression of these factors in astrocytes. Despite the upregulation of these factors in M1 stimulated astrocytes there were no significant effects on OPC in vitro. All astrocyte supernatants induced proliferation of A2B5 OPC and inhibited differentiation of OPC into mature oligodendrocytes. A trend toward enhanced migration of OPC was induced by M1 stimulated astrocytes. Our data suggest that M1-like microglia may potentially influence OPC and remyelination indirectly via astrocytes by inducing the expression of respective growth factors, however, this has no significant effect in addition to the already strong effects of unstimulated astrocytes on OPC. Nevertheless, the observed effect may be of relevance in other pathophysiological scenarios.