Astrocytes play a key role by providing antioxidant support to nearby neurons under oxidative stress. We have previously demonstrated that in vitro astroglial subtype 3 metabotropic glutamate receptor (mGlu3R) is neuroprotective. However, its role during aging has been poorly explored.

Our study aimed to determine whether LY379268, an mGlu3R agonist, exerts an antioxidant effect on aged cultured rat astrocytes.

Aged cultured astrocytes obtained after 9-weeks (9w) in vitro were positive for β-galactosidase stain, showed decreased mGlu3R and glutathione (GSH) levels and superoxide dismutase (SOD) activity, while nuclear erythroid factor 2 (Nrf2) protein levels, reactive oxygen species (ROS) production and apoptosis were increased.

Treatment of 9w astrocytes with LY379268 resulted in an increase in mGlu3R and Nrf2 protein levels and SOD activity, and decreased mitochondrial ROS levels and apoptosis.

mGlu3R activation in aged astrocytes also prevented hippocampal neuronal death induced by Aβ_1-42 in co-culture assays.

We conclude that activation of mGlu3R in aged astrocytes had an anti-oxidant effect and protected hippocampal neurons against Aβ-induced neurotoxicity. The present study suggests mGlu3R activation in aging astrocytes as a therapeutic strategy to slow down age-associated neurodegeneration.

星形胶质细胞通过为氧化应激下的附近神经元提供抗氧化支持而发挥关键作用。我们之前已经证明体外星形胶质细胞亚型 3 代谢型谷氨酸受体 (mGlu3R) 具有神经保护作用。然而，它在衰老过程中的作用尚未得到很好的探索。

我们的研究旨在确定 LY379268（一种 mGlu3R 激动剂）是否对老年培养的大鼠星形胶质细胞产生抗氧化作用。

体外9 周 (9w) 后获得的老化培养星形胶质细胞对 β-半乳糖苷酶染色呈阳性，显示出 mGlu3R 和谷胱甘肽 (GSH) 水平以及超氧化物歧化酶 (SOD) 活性降低，而核红细胞因子 2 (Nrf2) 蛋白水平、反应性氧（ROS）产生和细胞凋亡增加。

用 LY379268 处理 9w 星形胶质细胞导致 mGlu3R 和 Nrf2 蛋白水平和 SOD 活性增加，并降低线粒体 ROS 水平和细胞凋亡。

在共培养试验中，老年星形胶质细胞中的 mGlu3R 激活也阻止了 Aβ _1-42诱导的海马神经元死亡。

我们得出结论，老化星形胶质细胞中 mGlu3R 的激活具有抗氧化作用并保护海马神经元免受 Aβ 诱导的神经毒性。本研究表明，老化星形胶质细胞中的 mGlu3R 激活可作为减缓与年龄相关的神经变性的治疗策略。