Autophagy suppresses microglial activation and enhances M2 polarization via the mTOR/ULK1 pathway after optic nerve crush
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Purpose
To investigate whether rapamycin can regulate microglial activation and polarization via mTOR and its downstream signals via autophagy both in vivo and in vitro .
Methods
The in vivo study used wild type C57BL/6 mice that were intraperitoneally injected with rapamycin (2 mg/kg) plus ONC. The BV2 cell line was used in the in vitro study and the cells were incubated with rapamycin (50 nM) or transfected with a specific mTOR-targeting small interfering RNA (si-mTOR). Immunohistochemical staining was used to observe the changes in the morphology and cell surface area of microglia and Weste blotting analysis was used for detection of the changes in the proteins related autophagy, microglia polarization and mTOR pathway after the retinal tissue or the cell samples were collected.
Results
These results indicate that rapamycin increases autophagy and M2 polarization by inhibiting p-mTOR in wild-type C57BL/6 mice in vivo . In the BV2 cell line, rapamycin and si-mTOR can enhance autophagy and promote M2 polarization by inhibiting the p-mTOR/p-Unc-51-like kinase 1 (p-ULK1) pathway.
Conclusions
In conclusion, this work contributes to the understanding of the complex interplay among rapamycin, autophagy and microglial activation/polarization, highlights the downstream signaling pathway of mTOR, and highlights the potential therapeutic effects of autophagy-modulating drugs in retinal neuroinflammation and neurodegeneration after TON.
