Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
In Vitro Cell Dev Biol Anim. 2023 May;59(5):366-380. doi: 10.1007/s11626-023-00777-z. Epub 2023 Jun 23.
Astrocytes play essential roles in the central nervous system (CNS), such as the regulation of glutamate metabolism, antioxidant defenses, and inflammatory/immune responses. Moreover, hypothalamic astrocytes seem to be crucial in the modulation of inflammatory processes, including those related to type I interferon signaling. In this regard, the polyphenol resveratrol has emerged as an important glioprotective molecule to regulate astrocyte functions. Therefore, this study aimed to investigate the immunomodulatory and protective effects of resveratrol in hypothalamic astrocyte cultures obtained from mouse depleted of type I interferon receptors (INF-α/β), a condition that can impair immune and inflammatory functions. Resveratrol upregulated glutamate transporter and glutamine synthetase gene expression, as well as modulated the release of wide range of cytokines and genes involved in the control of inflammatory response, besides the expression of adenosine receptors, which display immunomodulatory functions. Resveratrol also increased genes associated with redox balance, mitochondrial processes, and trophic factors signaling. The putative genes associated with glioprotective effects of resveratrol, including nuclear factor erythroid derived 2 like 2 (Nrf2), heme oxygenase 1 (HO-1), sirtuin 1 (SIRT1), and phosphoinositide 3-kinase (PI3K)/Akt, were further upregulated by resveratrol. Thus, our data show that resveratrol was able to modulate key genes associated with glial functionality and inflammatory response in astrocyte cultures derived from IFNα/βR mice. These data are in agreement with previous results, reinforcing its glioprotective effects even in hypothalamic astrocytes with altered inflammatory and immune signaling. Finally, this polyphenol can prepare astrocytes to better respond to injuries, including those associated with neuroimmunology defects.
星形胶质细胞在中枢神经系统 (CNS) 中发挥着重要作用，例如调节谷氨酸代谢、抗氧化防御和炎症/免疫反应。此外，下丘脑星形胶质细胞似乎在调节炎症过程中至关重要，包括与 I 型干扰素信号相关的过程。在这方面，多酚白藜芦醇已成为调节星形胶质细胞功能的重要神经保护分子。因此，本研究旨在研究白藜芦醇对缺乏 I 型干扰素受体 (INF-α/β) 的小鼠下丘脑星形胶质细胞培养物的免疫调节和保护作用，这种情况会损害免疫和炎症功能。白藜芦醇上调谷氨酸转运体和谷氨酰胺合成酶基因的表达，并调节广泛的细胞因子和参与炎症反应控制的基因的释放，此外还调节具有免疫调节功能的腺苷受体的表达。白藜芦醇还增加了与氧化还原平衡、线粒体过程和营养因子信号转导相关的基因。与白藜芦醇的神经保护作用相关的假定基因，包括核因子红细胞衍生 2 样 2 (Nrf2)、血红素加氧酶 1 (HO-1)、沉默调节蛋白 1 (SIRT1) 和磷酸肌醇 3-激酶 (PI3K)/Akt，也被白藜芦醇进一步上调。因此，我们的数据表明，白藜芦醇能够调节与星形胶质细胞培养物中神经胶质功能和炎症反应相关的关键基因，这些基因来源于 IFNα/βR 小鼠。这些数据与先前的结果一致，即使在炎症和免疫信号改变的下丘脑星形胶质细胞中，也增强了其神经保护作用。最后，这种多酚可以使星形胶质细胞更好地应对损伤，包括与神经免疫缺陷相关的损伤。
