Astrocytes retain their antioxidant capacity into advanced old age.
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.
Liddell
Jeff R
JR
School of Psychology & Psychiatry, Monash University, Clayton, Victoria, Australia. jliddell@unimelb.edu.au
Robinson
Stephen R
SR
Dringen
Ralf
R
Bishop
Glenda M
GM
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000502:physiology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D039481:CD11b Antigen / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism
D039481:CD11b Antigen; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D019328:Buthionine Sulfoximine; D006861:Hydrogen Peroxide; D005978:Glutathione