The secretome of M1 and M2 microglia differently regulate proliferation, differentiation and survival of adult neural stem/progenitor cell

Abstract

AbstractMicroglia has been reported to be able to regulate the proliferation, differentiation and survival of adult Neural stem/progenitor cells (NSPCs) by modulating the microenvironment, which results in different consequences of adult neurogenesis. However, whether the microglial activation is beneficial or harmful to NSPCs is still controversial because of the complexity and variability of microglial activation phenotypes. In this study, we detected the expression levels of M1 marker and M2 marker in IFN-γ- and IL-4-induced microglia at different time, respectively. The phenotypic markers of M1 and M2 microglia were stable for 24 h after removal of IFN-γ and IL-4 intervention, but exhibited different change patterns during the next 24 h. Then, the adult NSPCs were treated by the conditioned medium from IFN-γ- and IL-4-activated microglia. The conditioned medium from IFN-γ-activated microglia promoted apoptosis and astroglial differentiation of NSPCs, while suppressed proliferation and neuronal differentiation of NSPCs. However, the conditioned medium from IL-4-activated microglia exhibited opposite effects on these physiological processes. In addition, the direct treatment of IFN-γ or IL-4 alone did not significantly affect the proliferation, differentiation and survival of NSPCs. These results suggest that the secretome of pro-inflammatory (M1) and anti-inflammatory (M2) microglia differently regulated the proliferation, differentiation and survival of adult NSPCs. These findings will help further study the biological mechanism of microglia regulating neurogenesis, and provide a therapeutic strategy for neurological diseases by regulating microglial phenotypes to affect neurogenesis.