Interactions between apolipoprotein E gene and dietary alpha-tocopherol influence cerebral oxidative damage in aged mice

Cerebral oxidative damage is a feature of aging and is increased in a numbe r of neurodegenerative diseases. We pursued the gene-environment interactio n of lack of apolipoprotein E (apoE) and modulation of dietary alpha -tocop herol on cerebral oxidative damage in aged male and female mice by quantify ing the major isomers of cerebral isoprostanes, derived from arachidonic ac id (AA) oxidation, and neuroprostanes, derived from docosahexaenoic acid (D HA) oxidation. Mice fed alpha -tocopherol-deficient, normal, or -supplement ed diet had undetectable, 4486 +/- 215, or 6406 +/- 254 ng of alpha -tocoph erol per gram of brain tissue ( p < 0.0001), respectively. Two factors, mal e gender and lack of apoE, combined to increase cerebral AA oxidation by 28 %, whereas three factors, male gender, lack of apoE, and deficiency in <alp ha>-tocopherol, combined to increase cerebral DHA oxidation by 81%. alpha - Tocopherol supplementation decreased cerebral isoprostanes but not neuropro stanes 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 alpha -tocopherol contributed differently to oxidative damage to cerebral AA and DHA in aged mice.