Oxidative Damage to Behavior During Aging

The proposition that free radicals may be an important factor in aging remains to be rigorously proven; but the presence of increased amounts of oxidized proteins in aging biological systems supports the notion. The results of new experiments in Mongolian gerbils indicate that the accumulation of oxidatively damaged proteins during aging may be a cause of behavioral deficits in aging experimental animals and that this chronic oxidation may be reversible with compounds that react with and stabilize free radicals. PBN (N-tert-butyl-alpha-phenyl nitrone), a spin-trapping compound, reacts with free radicals and yields a stable nitroxyl product. PBN offers protection from, and traps free radicals during, ischemia-reperfusion-mediated injury to heart and brain of experimental animals. Daily administration of PBN to old gerbils causes a decrease in the amount of oxidized protein and an increase in both glutamine synthetase and neutral protease activity in brain, as well as a decrease in the number of errors made in the radial-arm maze test for memory. In other words, PBN administration reversed the chemical and behavioral parameters of the older gerbils to nearly those values observed in the younger gerbils. Furthermore, after cessation of PBN administration, the amount of both oxidized protein as well as glutaminemore » synthetase and neutral protease activities gradually returned to the values found in normal, older gerbils. PBN did not have these effects in young gerbils. « less