DIET AND BRAIN AGING IN A CANINE MODEL
Cotman, C.W.1*, Head, E.1, Muggenburg, B.A.2, and Milgram, N.W.3
1University of California, Irvine, Irvine, CA 92697; 2Lovelace Respiratory Research Laboratory, Albuquerque, NM 87108-5127; 3University of Toronto, Scarborough, Ontario, Canada M1C 1A4
Advanced age is accompanied by cognitive decline indicative of central
nervous system dysfunction. One possibly critical causal factor is
oxidative stress. Accordingly, we studied the effects of dietary
antioxidants and age in a canine model of aging that parallels the key
features of cognitive decline and neuropathology in humans. Old and
young animals were placed on either a standard control food, or a food
enriched with a broad spectrum of antioxidants and mitochondrial
enzymatic cofactors. The dietary components included vitamin E,
vitamin C, fruits, vegetables, alpha-lipoic acid and l-carnitine. At
multiple time points during the 2.5 year intervention study, changes in
different types of learning abilities (landmark discrimination, oddity
discrimination, size discrimination and reversal learning, intensity
discrimination learning and reversal) and spatial memory were examined.
Overall, old animals performed more poorly than young animals. However,
this age-associated decline was reduced in the animals fed the enriched
food, particularly on the more difficult learning tasks. These results
indicate that maintenance on foods fortified with complex mixtures of
antioxidants can partially counteract the deleterious effects of aging
on cognition. A series of neurobiological studies are currently
underway. The first experiments indicate that the diet rich in
antioxidants slowed, but did not reverse, senile plaque formation in
the aged canines. The largest reduction in A? was achieved in
posterior cortical regions including the parietal and occipital
cortices, which accumulate plaque pathology at later ages in the
canine. These regions showed reduced A? deposition in the
antioxidant-treated aged animals. Thus, a diet rich in antioxidants
may slow cognitive decline and reduce senile plaque formation in a
higher mammalian species and may be useful for promoting successful
brain aging in humans.
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