Cerebral oxidative damage is a feature of aging and is increased in a number of neurodegenerative diseases. We pursued the gene-environment interaction of lack of apolipoprotein E (apoE) and modulation of dietary α-tocopherol on cerebral oxidative damage in aged male and female mice by quantifying the major isomers of cerebral isoprostanes, derived from arachidonic acid (AA) oxidation, and neuroprostanes, derived from docosahexaenoic acid (DHA) oxidation. Mice fed α-tocopherol-deficient, normal, or -supplemented diet had undetectable, 4486 ± 215, or 6406 ± 254 ng of α-tocopherol per gram of brain tissue (p < 0.0001), respectively. Two factors, male gender and lack of apoE, combined to increase cerebral AA oxidation by 28%, whereas three factors, male gender, lack of apoE, and deficiency in α-tocopherol, combined to increase cerebral DHA oxidation by 81%. α-Tocopherol supplementation decreased cerebral isoprostanes but not neuroprostanes and enhanced DHA, but not AA, endoperoxide reduction in vivo and in vitro. These results demonstrated that the interaction of gender, inherited susceptibilities, and dietary α-tocopherol contributed differently to oxidative damage to cerebral AA and DHA in aged mice.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Neuroscience|
|State||Published - Aug 15 2001|
- Apolipoprotein E
- Oxidative damage