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Coupling of GPR30 mediated neurogenesis and protection with astroglial Aromatase-STAT3 signaling in rat hippocampus after global cerebral ischemia
Molecular and Cellular Endocrinology ( IF 3.8 ) Pub Date : 2021-07-15 , DOI: 10.1016/j.mce.2021.111394
Lu Wang 1 , Jiahao Liu 1 , Jing Xu 2 , Wenli Zhang 1 , Ruimin Wang 3
Affiliation  

Our previous study revealed that G-protein-coupled estrogen receptor-30 (GPR30) agonist G1 serves as a viable alternative neuroprotectant of 17β-estradiol (E2) to attenuate neuroinflammation and improve cognitive function after global cerebral ischemia (GCI). Aromatase, the key enzyme of E2 biosynthesis, is widely expressed in animal and human brain, and its expression and activity are mediated by selective estrogen receptor modulators. In the present study, we explored the long-term protective and reparative effects of G1 in ovariectomized rats after GCI. We used the aromatase inhibitor letrozole to elucidate whether G1 and brain-derived E2 together induce beneficial effects. Our results showed that G1 administration for 28 days a) significantly increased neurogenesis in the hippocampal sub-granular zone and CA1 regions; b) declined CA1 neuronal impairment in a long-term fashion; c) enhanced expression of synaptic proteins and cognitive function; d) and prevented reactive astrocytes loss, wherein aromatase and brain-derived estrogen levels were markedly increased. Additionally, expression and activation of transducer and activator of transcription 3 (STAT3) were increased in CA1 astrocytes of G1-treated animals. Letrozole abolished all of the observed benefits of G1. Our results suggest that GPR30 activation mediates long-term neuroprotection and neurogenesis in the hippocampus following GCI, with potential mechanism coupling with the activation of astroglial aromatase-STAT3 signaling.



中文翻译:

GPR30介导的神经发生和保护与全脑缺血后大鼠海马中星形胶质细胞芳香酶-STAT3信号传导的耦合

我们之前的研究表明,G 蛋白偶联雌激素受体 30 (GPR30) 激动剂 G1 可作为 17β-雌二醇 (E2) 的替代神经保护剂,以减轻全脑缺血 (GCI) 后的神经炎症和改善认知功能。芳香酶是E2生物合成的关键酶,在动物和人脑中广泛表达,其表达和活性受选择性雌激素受体调节剂介导。在本研究中,我们探讨了 GCI 后 G1 对去卵巢大鼠的长期保护和修复作用。我们使用芳香酶抑制剂来曲唑来阐明 G1 和脑源性 E2 是否一起诱导有益作用。我们的结果表明,G1 给药 28 天 a) 显着增加海马亚颗粒区和 CA1 区的神经发生;b) 长期减少 CA1 神经元损伤;c) 突触蛋白和认知功能的表达增强;d) 并防止反应性星形胶质细胞丢失,其中芳香酶和脑源性雌激素水平显着增加。此外,在 G1 治疗动物的 CA1 星形胶质细胞中,传感器和转录激活因子 3 (STAT3) 的表达和激活增加。来曲唑消除了 G1 所观察到的所有益处。我们的研究结果表明,GPR30 激活介导 GCI 后海马中的长期神经保护和神经发生,其潜在机制与星形胶质芳香化酶-STAT3 信号传导的激活有关。其中芳香化酶和脑源性雌激素水平显着增加。此外,在 G1 治疗动物的 CA1 星形胶质细胞中,传感器和转录激活因子 3 (STAT3) 的表达和激活增加。来曲唑消除了 G1 所观察到的所有益处。我们的研究结果表明,GPR30 激活介导 GCI 后海马中的长期神经保护和神经发生,其潜在机制与星形胶质芳香化酶-STAT3 信号传导的激活有关。其中芳香化酶和脑源性雌激素水平显着增加。此外,在 G1 治疗动物的 CA1 星形胶质细胞中,传感器和转录激活因子 3 (STAT3) 的表达和激活增加。来曲唑消除了 G1 所观察到的所有益处。我们的研究结果表明,GPR30 激活介导 GCI 后海马中的长期神经保护和神经发生,其潜在机制与星形胶质芳香化酶-STAT3 信号传导的激活有关。

更新日期:2021-07-21
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