RELATIONSHIP BETWEEN AGE AND GSH METABOLISM IN SYNAPTOSOMES OF RAT CEREBRAL-CORTEX

A comprehensive analysis on glutathione metabolism in rat cerebral cor tex synaptosomes as a function of age was performed. All different glu tathione system components (GSH, GSSG, total GSH, and GSH redox index) changed significantly only during aging. GSH, total GSH, and GSH redo x index decreased by about 40%, 24%, and 52%, respectively, while GSSG showed a remarkable increase of about 60%. On the contrary, some GSH- related enzyme activities showed characteristic changes both during gr owth and aging. GSH peroxidase and GSH-S-transferase activities signif icantly increased both during growth and aging, GSH reductase and gamm a-glutamylcysteine synthetase activities showed lower levels only duri ng aging, while glucose-6-phosphate dehydrogenase activity did not cha nge throughout the life of the rat. The results obtained suggest an in crease of the oxidative status due to a reduced antioxidant capacity o f the GSH system in the synaptosomal compartment during aging. The mai n cause of these metabolic modifications is a lowering of the rates of both GSSG reduction to GSH and GSH synthesis. Moreover, an irreversib le loss of GSH as GSH-S-conjugates due to a high detoxification mechan ism during aging is also possible. These alterations in glutathione me tabolism, found mainly during aging in rat cerebral cortex synaptosome s may contribute to clarify some aspects of cerebral diseases.