Long-term antioxidant supplementation attenuates oxidative stress markers and cognitive deficits in senescent-accelerated OXYS rats

Oxidative damage of biomolecules increases with age and is postulated to be a major causal factor of various neurodegenerative disorders. Consequently, the concept of neuroprotection by antioxidants has been developed. Recently we have shown that the behaviour of young senescent-accelerated OXYS rats is similar to the behaviour of old Wistar animals. To determine the role of oxidative stress in this phenomenon we investigated age-related changes in protein carbonyls (PrC), lipid peroxides (LP), reduced glutathione (GSH), alpha-tocopherol (TP) and SOD activity in the brain of OXYS and Wistar rats. We also studied the effect of long-term supplementation with bilberry extract (2 g/kg of diet) and Vitamin E (140 mg/kg of diet) on oxidative stress markers and on learning in passive avoidance test. In both rat strains LP, PrC and TP increased with age and at 24 months PrC was significantly higher (p < 0.0001) in OXYS rats. At 3 months GSH was higher and SOD activity was lower in OXYS rats than in Wistar rats. SOD activity decreased with age in OXYS whereas increased in Wistar rats. Cognitive impairments in OXYS rats were manifested earlier than significant differences in the level of brain oxidative stress markers between two strains. By contrast, differences in antioxidant systems of Wistar and OXYS rats were registered at 3 months. Antioxidants attenuated cognitive deficits in OXYS rats, providing evidence for therapeutic role of antioxidants. Nevertheless, the exact mechanisms of neuroprotective effects of antioxidants in vivo and the real impact of oxidative stress on the development of cognitive impairments in OXYS rats still needs to be further investigated. (c) 2005 Elsevier Inc. All rights reserved.