Objectives: 

Anti-aging therapies as the caloric restriction and substances that defense against oxidative stress reduce cognitive decline. Also, the neuroprotective pathway mediated by sirtuin 1 has recently drawn attention. The chronic effects of the antioxidants resveratrol and α-tocopherol (vitamin E) on cognitive performance in old rats were compared among themselves and with the control group.

Materials: 

To evaluate memory processes, two different tests were used, the spatial working memory 8-arm radial maze, and the novel object recognition, a form of non-spatial working memory. Old (19-20 months) Wistar male rats were treated intraperitoneal with resveratrol (20 mg/kg), α-tocopherol (20 mg/kg) or vehicle (corn oil, 1 ml/kg) for 28 days. Trials on radial maze were judged complete when rats had chosen all 8 baited arms or spent 20 min in the trial. Re-entered or non entered arms were computed as errors. In the novel object recognition, exploration was defined as direct contact of the nose with the object, or as pointing the nose to the object at a distance of 1 cm.

Results: 

Chronic vehicle treatment did not change working memory tasks along the treatment. A significant improvement in radial maze test was observed after chronic treatment with resveratrol respect to controls: 31% reduction in trial time and 38% errors reduction. A 25% reduction in trial time accompanied with an increase in errors number (20%) was observed after 28 days of α-tocopherol treatment. Moreover, the time spent exploring the novel compared to the familiar object increased 2 times in the group of rats treated with resveratrol, while α-tocopherol treated rats spent the same time to explore the objects along the treatment.

Conclusions: 

Resveratrol but not α-tocopherol clearly improved working memory. The results suggest that the sirtuin 1 enhancer resveratrol which has been reported to mimic the ability of dietary restriction is a promising mechanism to protect against the age cognitive decline.