Suppression of age-related changes in mouse hippocampal CA3 nerve cells by a free radical scavenger

This study was designed to evaluate the relationship between oxygen free radicals and age-related morphological changes in hippocampal nerve cells using K-7259 (N,N' bis[4-(3,4,5-trimethoxyphenyl)butyl] homopiperazine dihydrochloride), a known neuro-protective agent. A chemiluminescence assay has shown that this agent is a potent free radical scavenger with an IC50 of 1.6 x 10(-5)M. Mice fed diets containing 10, 20, 40 mg/kg/day of K-7259, for periods ranging from 25 to 40 or 50 weeks of age were used as test groups, and 10-, 20-, 30-, 40-, and 50-week-old mice fed a standard diet were used as controls. We measured the number and area of pyramidal nerve cells within a defined frame in the hippocampal CA3 field using an image analyzer and the density of nerve cells by the disector method. These values decreased gradually in controls as expected, and the number and area yielded a significant difference between control mice at the ages of 10 and 30 weeks. As compared with the corresponding controls, all test groups had greater cell numbers (statistical significance at 40 weeks in the 40 mg/kg/day group) and density, while cell areas were greater in all but a 10 mg/kg/day group (statistical significance at 50 weeks). In summary, the free radical scavenger K-7259 forestalled an age-related decrease in the number and size of hippocampal CA3 nerve cells, thus suggesting that free radicals play an important role in the cellular morphological changes which appear with age.