School of Psychology & Psychiatry, Monash University, Clayton, Victoria, Australia.
Glia. 2010 Sep;58(12):1500-9. doi: 10.1002/glia.21024.
Oxidative stress has been implicated in the progression of ageing and in many age-related neurodegenerative conditions. Astrocytes play a major role in the antioxidant protection of the brain, yet little is known about how the antioxidant defenses of astrocytes change across the lifespan. This study assessed the antioxidant capacity and glutathione metabolism of astrocytes cultured from the brains of neonatal (<24 h old), mature (12-month-old), old (25-month-old), and senescent (31-month-old) C57BL/6J mice. When exposed to 100 microM hydrogen peroxide, mature, old, and senescent astrocytes cleared the peroxide approximately 30% more slowly than neonatal astrocytes. This difference persisted when catalase was inhibited by 3-aminotriazole, but was abolished when glutathione was depleted by application of buthionine sulfoximine, suggesting a deficit in the glutathione system. Correspondingly, the specific glutathione reductase activity of mature, old, and senescent astrocytes was approximately 30% lower than that of neonatal cultures, whereas no age-related change was observed in the specific activities of glutathione peroxidase, catalase, or in total antioxidant capacity. In addition, the specific rate of glutathione export was almost identical in mature, old, and senescent astrocytes, but was more than double that of neonatal astrocytes. These results indicate that the antioxidant capacity and glutathione metabolism of astrocytes are preserved from mature adulthood into senescence. It is concluded that the oxidative stress seen in ageing brains is likely due to factors extrinsic to astrocytes, rather than to an impairment of the antioxidative functions of astrocytes.
氧化应激与衰老的进展以及许多与年龄相关的神经退行性疾病有关。星形胶质细胞在大脑的抗氧化保护中起着重要作用，但人们对星形胶质细胞的抗氧化防御如何随年龄变化知之甚少。本研究评估了从小鼠大脑中培养的星形胶质细胞的抗氧化能力和谷胱甘肽代谢，这些小鼠分别为新生（<24 小时）、成熟（12 个月）、老年（25 个月）和衰老（31 个月）的 C57BL/6J 小鼠。当暴露于 100µM 过氧化氢时，成熟、老年和衰老的星形胶质细胞清除过氧化物的速度比新生星形胶质细胞慢约 30%。当过氧化氢酶被 3-氨基三唑抑制时，这种差异仍然存在，但当应用丁硫氨酸亚砜亚胺耗尽谷胱甘肽时，这种差异就消失了，这表明谷胱甘肽系统存在缺陷。相应地，成熟、老年和衰老的星形胶质细胞的特异性谷胱甘肽还原酶活性比新生培养物低约 30%，而谷胱甘肽过氧化物酶、过氧化氢酶或总抗氧化能力的特异性活性在年龄相关变化中没有观察到。此外，成熟、老年和衰老的星形胶质细胞的特异性谷胱甘肽输出率几乎相同，但比新生星形胶质细胞高两倍多。这些结果表明，星形胶质细胞的抗氧化能力和谷胱甘肽代谢从成熟成年期到衰老期都得到了保留。因此可以得出结论，衰老大脑中的氧化应激很可能是由于星形胶质细胞以外的因素引起的，而不是由于星形胶质细胞的抗氧化功能受损所致。
