星形胶质细胞介导的脆性 X 小鼠模型中 ROS 稳态的破坏

Astrocyte-mediated disruption of ROS homeostasis in Fragile X mouse model.

Keywords：Antioxidants, Astrocyte, Fragile X Syndrome, Mitochondrial respiration, Mouse model, Oxidative stress, Reactive species  

关键词：抗氧化剂、星形胶质细胞、脆性 X 综合征、线粒体呼吸、小鼠模型、氧化应激、反应性物种 

哺乳动物：小鼠
作者：Vandenberg Gregory G、Dawson Neal J、Head Alison、Scott Graham R、Scott Angela L

出版期刊：《Neurochem Int》（2021）

Abstract：

Astrocytes, glial cells within the brain, work to protect neurons during high levels of activity by maintaining oxidative homeostasis via regulation of energy supply and antioxidant systems. In recent years, mitochondrial dysfunction has been highlighted as an underlying factor of pathology in many neurological disorders. In animal studies of Fragile X Syndrome (FXS), the leading genetic cause of autism, higher levels of reactive oxygen species, lipid peroxidation, and protein oxidation within the brain indicates that mitochondria function is also altered in FXS. Despite their integral contribution to redox homeostasis within the CNS, the role of astrocytes on the occurrence or progression of neurodevelopmental disorders in this way is rarely considered. This study specifically examines changes to astrocyte mitochondrial function and antioxidant expression that may occur in FXS. Using the Fmr1 knockout (KO) mouse model, mitochondrial respiration and reactive oxygen species (ROS) emission were analyzed in primary cortical astrocytes. While mitochondrial respiration was similar between genotypes, ROS emission was significantly elevated in Fmr1 KO astrocytes. Notably, NADPH-oxidase 2 expression in Fmr1 KO astrocytes was also enhanced but only changes in catalase antioxidant enzyme expression were noted. Characterization of astrocyte factors involved in redox imbalance is invaluable to uncovering potential sources of oxidative stress in neurodevelopmental disorders and more specifically, the intercellular mechanisms that contribute to dysfunction in FXS.

文章摘要：

星形胶质细胞是大脑中的神经胶质细胞，通过调节能量供应和抗氧化系统来维持氧化稳态，从而在高水平活动期间保护神经元。近年来，线粒体功能障碍已被强调为许多神经系统疾病的潜在病理因素。在脆性 X 综合征 (FXS) 的动物研究中，自闭症的主要遗传原因、较高水平的活性氧、脂质过氧化和大脑内的蛋白质氧化表明线粒体功能也在 FXS 中发生了改变。尽管星形胶质细胞对中枢神经系统内的氧化还原稳态做出了不可或缺的贡献，但星形胶质细胞以这种方式在神经发育障碍的发生或进展中的作用很少被考虑。这项研究专门检查了 FXS 中可能发生的星形胶质细胞线粒体功能和抗氧化表达的变化。使用 Fmr1 敲除 (KO) 小鼠模型，在初级皮质星形胶质细胞中分析线粒体呼吸和活性氧 (ROS) 排放。虽然基因型之间的线粒体呼吸相似，但 Fmr1 KO 星形胶质细胞的 ROS 排放显着升高。值得注意的是，Fmr1 KO 星形胶质细胞中 NADPH 氧化酶 2 的表达也有所增强，但仅注意到过氧化氢酶抗氧化酶表达的变化。参与氧化还原失衡的星形胶质细胞因子的表征对于揭示神经发育障碍中氧化应激的潜在来源，更具体地说，是揭示导致 FXS 功能障碍的细胞间机制非常宝贵。

点击链接即可查看和下载文章：https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(21)00082-6

文章题目、关键词与摘要译文仅用于参考。