Antioxidants and cognitive training interact to affect oxidative stress and memory in APP/PSEN1 mice.
The present study investigated the relationships among oxidative stress, beta-amyloid and cognitive abilities in the APP/PSEN1 double-transgenic mouse model of Alzheimer's disease. In two experiments, long-term dietary supplements were given to aged APP/PSEN1 mice containing vitamin C alone (1 g/kg diet; Experiment 1) or in combination with a high (750 IU/kg diet, Experiments 1 and 2) or lower (400 IU/kg diet, Experiment 2) dose of vitamin E. Oxidative stress, measured by F(4)-neuroprostanes or malondialdehyde, was elevated in cortex of control-fed APP/PSEN1 mice and reduced to wild-type levels by vitamin supplementation. High-dose vitamin E with C was less effective at reducing oxidative stress than vitamin C alone or the low vitamin E+C diet combination. The high-dose combination also impaired water maze performance in mice of both genotypes. In Experiment 2, the lower vitamin E+C treatment attenuated spatial memory deficits in APP/PSEN1 mice and improved performance in wild-type mice in the water maze. Amyloid deposition was not reduced by antioxidant supplementation in either experiment.
Harrison
F E
FE
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-0475, USA. fiona.harrison@vanderbilt.edu
Allard
J
J
Bixler
R
R
Usoh
C
C
Li
L
L
May
J M
JM
McDonald
M P
MP
D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000172:deficiency / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis; D001522:Behavior, Animal / Q000502:physiology; D001923:Brain Chemistry; D003071:Cognition; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D008099:Liver / Q000737:chemistry; D008297:Male; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D058225:Plaque, Amyloid / Q000378:metabolism; D053764:Presenilin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014810:Vitamin E / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis
D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D053764:Presenilin-1; D014810:Vitamin E; D001205:Ascorbic Acid