GPR17 Negatively Regulates Oligodendrocyte Differentiation and Myelination In Vitro

Background: GPR17 is restricted to oligodendrocyte lineage cells but is down-regulated during the peak period of myelination and in adulthood. However, it is unclear whether there is a bi-directional regulation between Olig1 and GPR17. Methods: The specific molecular mechanism of oligodendrocyte injury caused by microglia activation remains unclear. In the present study, we investigated the role of GPR17 in the myelination of rat pre-OLs to OLs by up-regulating or down-regulating GPR17 expression in OLs and elucidate the role of GPR17 in ameliorating the OL injury induced by LPS-activated microglia. Results: GPR17-overexpressing cells have been shown to inhibit pre-OL maturation, and Olig1 and GPR17 could not form a bi-directional regulation loop. In contrast, the LPS indeed slowed down the cell proliferation, and siGPR17 could reverse the inhibitory effect caused by LPS and microglial. Conclusions: These results indicated that siGPR17 can treat the cell injury by promoting OL myelination. The present study suggests that targeted inhibition of the GPR17 receptor signaling together with other treatments might augment remyelination by immature oligodendrocytes following a variety of pathological insults.