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

IF 3.8 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemical Research Pub Date : 2025-03-29 DOI:10.1007/s11064-025-04373-3

Kang Ma, Jiandong Niu, Liang Zeng, Jianying Tian, Yawen Zhang

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Abstract

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 β-Galactosidase (SA-β-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-α (TNF-α) and interleukin-1β (IL-1β) and increased arginase-1 (Arg1), α7 nicotinic acetylcholine receptor (α7nAChR), nuclear factor erythrocyte 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression. Moreover, after administration of α7nAChR selective antagonist methyllycaconitine citrate (MLA), our results showed that SAM enhanced expression of α7nAChR, 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 α7nAChR/Nrf2/HO-1 pathway.

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SAM通过α7nAChR/Nrf2/HO-1信号通路调节小胶质细胞M1/M2极化，减轻神经炎症

小胶质细胞是神经炎症的驱动因素。小胶质细胞的激活在衰老的发病机制中起着关键作用。然而，小胶质细胞在衰老过程中激活的机制仍未完全了解。在这里，我们研究了s -腺苷蛋氨酸（SAM）在衰老过程中的作用及其与小胶质细胞激活的相互作用。本研究通过细胞计数试剂盒-8 （CCK8）、衰老相关β-半乳糖苷酶（SA-β-gal）染色、western blot和免疫荧光等方法研究SAM对d -半乳糖（D-gal）处理BV2细胞的影响及其分子机制。我们发现D-gal可以诱导小胶质细胞衰老。SAM干预导致诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子-α (TNF-α)和白细胞介素-1β (IL-1β)水平显著降低，精氨酸酶-1 （Arg1）、α7烟碱乙酰胆碱受体（α7nAChR）、核因子红细胞2相关因子2 （Nrf2）和血红素加氧酶1 （HO-1）表达升高。此外，我们的研究结果显示，与MLA + D-gal组相比，给予α7nAChR选择性拮抗剂MLA （methyllycaaconitine citrate）后，SAM增强α7nAChR、Nrf2和HO-1的表达，促进小胶质细胞从M1亚型向M2亚型转化，并降低促炎细胞因子。这些结果表明，SAM通过α7nAChR/Nrf2/HO-1通路抑制小胶质细胞极化，从而减轻神经炎症。图形抽象

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来源期刊

Neurochemical Research 医学-神经科学

CiteScore

7.70

自引率

2.30%

发文量

320

审稿时长

6 months

期刊介绍： Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.