Chronic antioxidant treatment improves the cognitive performance of aged rats.

Free radicals and oxidative damage have been implicated in brain aging and several neurodegenerative diseases. The purpose of the present study was to determine whether antioxidants could alleviate age-associated cognitive and motor changes. Aged 24-month-old male Sprague-Dawley rats were treated for 4-5 months with daily i.p. injections of spin-trapping compound phenyl-alpha-tert-butylnitrone (PBN; 32 mg/kg) and alpha-tocopherol (200 mg/kg) or with vehicles. Antioxidant-treated animals also received ascorbate in their drinking water. In Morris water maze testing after two months, antioxidant-treated rats exhibited significantly greater memory retention than vehicle-treated rats in water maze testing. Subsequent tests for passive avoidance behavior and motor activity/skill revealed no effect of antioxidant treatment. In a separate group of aged 33-month-old rats that received the same combination of antioxidants for only 14 days, antioxidant treatment did not affect basal levels of brain lipid peroxidation (as indexed by TBAR formation) compared to controls. The results of this study provide initial evidence that chronic antioxidant treatment can improve cognitive function during aging, thus supporting the 'free radical hypothesis of aging' related to brain function.