Lei Ming, Hua Xiangdong, Xiao Ming, Ding Jiong, Han Qunying, Hu Gang
Key Laboratory of Neurodegeneration of Jiangsu Province, Department of Anatomy, Histology and Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
Biochem Biophys Res Commun. 2008 May 16;369(4):1082-7. doi: 10.1016/j.bbrc.2008.02.151. Epub 2008 Mar 7.
Astrocyte dysfunction is implicated in course of various age-related neurodegenerative diseases. Chronic injection of d-galactose can cause a progressive deterioration in learning and memory capacity and serve as an animal model of aging. To investigate the involvement of astrocytes in this model, oxidative stress biomarkers, biochemical and pathological changes of astrocytes were examined in the hippocampus of the rats with six weeks of d-galactose injection. d-galactose-injected rats displayed impaired antioxidant systems, an increase in nitric oxide levels, and a decrease in reduced glutathione levels. Consistently, western blotting and immunostaining of glial fibrillary acidic protein showed extensive activation of astrocytes. Double-immunofluorescent staining further showed activated astrocytes highly expressed inducible nitric oxide synthase. Electron microscopy demonstrated the degeneration of astrocytes, especially in the aggregated area of synapse and brain microvessels. These findings indicate that impairments of astrocytes are involved in oxidative stress-induced brain aging by chronic injection of d-galactose.
星形胶质细胞功能障碍与多种年龄相关神经退行性疾病的病程有关。长期注射d-半乳糖可导致学习和记忆能力逐渐衰退，并可作为衰老的动物模型。为了研究星形胶质细胞在该模型中的作用，对注射d-半乳糖六周的大鼠海马体中星形胶质细胞的氧化应激生物标志物、生化和病理变化进行了检测。注射d-半乳糖的大鼠表现出抗氧化系统受损、一氧化氮水平升高和还原型谷胱甘肽水平降低。同样，胶质纤维酸性蛋白的蛋白质印迹法和免疫染色显示星形胶质细胞广泛激活。双重免疫荧光染色进一步显示激活的星形胶质细胞高表达诱导型一氧化氮合酶。电子显微镜显示星形胶质细胞退化，尤其是在突触和脑微血管的聚集区域。这些发现表明，长期注射d-半乳糖导致的星形胶质细胞损伤参与了氧化应激诱导的脑衰老过程。
