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Astrocytes retain their antioxidant capacity into advanced old age
Author(s) -
Liddell Jeff R.,
Robinson Stephen R.,
Dringen Ralf,
Bishop Glenda M.
Publication year - 2010
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.21024
Subject(s) - glutathione , glutathione reductase , biology , ageing , oxidative stress , antioxidant , glutathione peroxidase , buthionine sulfoximine , catalase , astrocyte , senescence , neuroglia , biochemistry , medicine , endocrinology , microbiology and biotechnology , central nervous system , enzyme , genetics
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 μM hydrogen peroxide, mature, old, and senescent astrocytes cleared the peroxide ∼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 ∼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. © 2010 Wiley‐Liss, Inc.