Antioxidant treatment with phenyl-alpha-tert-butyl nitrone (PBN) improves the cognitive performance and survival of aging rats.
Accumulating evidence has implicated free radical production and resultant oxidative damage as a major contributing factor in brain aging and cognitive decline. In the present study, aging 24-month-old rats were chronically treated with the synthetic spin-trapping antioxidant phenyl-alpha-tert-butyl nitrone (PBN) for up to 9.5 months. Chronic PBN treatment (1) improved the cognitive performance of aged rats in several tasks, (2) resulted in greater survival during the treatment period, and (3) decreased oxidative damage within brain areas important for cognitive function. These results not only provide a direct linkage between free radicals/oxidative damage and cognitive performance in old age, but also suggest that synthetic brain antioxidants could be developed to treat or prevent age-associated cognitive impairment and Alzheimer's disease.
Sack
C A
CA
Department of Biology and Institute on Aging, University of South Florida, Tampa 33620, USA.
Socci
D J
DJ
Crandall
B M
BM
Arendash
G W
GW
D000375:Aging / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009589:Nitrogen Oxides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D016019:Survival Analysis
D000975:Antioxidants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone