SAM Alleviates Neuroinflammation by Regulating M1/M2 Polarization of Microglia Through α7nAChR/Nrf2/HO-1 Signaling Pathway

Microglia are the drivers of neuroinflammation. Microglia activation plays a critical role in the pathogenesis of aging. However, the mechanisms underlying microglial activation during aging are still not fully understood. Here, we investigated the role of S-adenosylmethionine (SAM) and its interplay with microglial activation in aging. In this study, we investigated the effect of SAM on BV2 cells treated with D-galactose (D-gal) and its molecular mechanism by Cell Counting Kit-8 (CCK8) assay, Senescence-associated beta-Galactosidase (SA-beta-gal) staining, western blot and immunofluorescence. We found that D-gal could induce microglia senescence. SAM intervention induced a significant decrease in the levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and increased arginase-1 (Arg1), alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR), nuclear factor erythrocyte 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression. Moreover, after administration of alpha 7nAChR selective antagonist methyllycaconitine citrate (MLA), our results showed that SAM enhanced expression of alpha 7nAChR, Nrf2 and HO-1, promoted the transformation of microglia from M1 to M2 subtype, and decreased the proinflammatory cytokines compared with MLA + D-gal group. These results suggest that SAM attenuates neuroinflammation by inhibiting microglia polarization through the alpha 7nAChR/Nrf2/HO-1 pathway.