AGE-RELATED REGIONAL CHANGES IN HYDROXYL RADICAL STRESS AND ANTIOXIDANTS IN GERBIL BRAIN

The levels of hydroxyl radicals and oxidized GSH have been examined as indices of oxidative stress in young (3 months), middle-aged (15 months), and old (20-24 months) gerbil brain hippocampus, cortex, and striatum. The hydroxyl radical stress was estimated by measuring the salicylate hydroxyl radical trapping products 2,5- and 2,3-dihydroxybenzoic acid. The stress was significantly higher in all three brain regions in middle-aged and old gerbils versus young animals (less-than-or-equal-to 66.0%). Regional comparisons showed that the stress was significantly higher in cortex than in either the hippocampus or striatum of the middle-aged and old gerbils (less-than-or-equal-to 32.0%). The ratio of oxidized to total GSH also increased progressively in middle-aged and old animals in all three brain regions (p < 0.05, less-than-or-equal-to 41.1%), further indicating a general age-related increase in oxidative stress. Parallel to this age-related increase in oxidative stress, a significant, albeit slight (8%), decrease in neuronal number in hippocampal CA1 region was observed in both the middle-aged and old animals. Possible differences in antioxidant levels were also examined. Total GSH levels were similar across age groups (variance < 1 2%). However, the regional comparison showed that it was highest in striatum in all age groups. The levels of alpha-tocopherol (vitamin E) were significantly higher in the middle-aged and old animals in all three regions (less-than-or-equal-to 70.4%). Vitamin E was highest in the hippocampus and the differences between the hippocampus and the cortex and striatum increased with age. Although of a lesser magnitude, significant increases in hippocampal total ascorbic acid level were also noted with age (p < 0.05, less-than-or-equal-to 10%). Ascorbic acid was the most regionally specific of the three antioxidants examined, with hippocampus > cortex > striatum for all age groups. The difference in ascorbic acid level between hippocampus and cortex also increased with age (less-than-or-equal-to 64.4%). The results suggest that the general age-related, regionally specific increases in oxidative stress stimulate the accumulation of antioxidants. It is interesting that the hippocampus, which is selectively vulnerable to various insults such as ischemia, epilepsy, and insulin-induced hypoglycemia, exhibits the greatest age-related increase in vitamin E and ascorbic acid, perhaps reflective of a greater impact of the progressive increase in baseline oxidative stress.