Abstract
Objective:We examined genetic and dietary challenge on hippocampal oxidative damage. Mice expressing (ApoE+/+) or lacking apolipoprotein E (ApoE-/-) were maintained on a standard diet or a high fat /high cholesterol (challenge) diet for 11-31 weeks. Similar levels of oxidative species were observed for ApoE+/+ and -/- mice maintained on the basal diet.Method:However, treatment of ApoE-/- homogenates with hydrogen peroxide and iron increased oxidative species by >100%, indicating an equivalent amount of potential oxidative species in latent form. We observed a time- and region-specific induction of oxidative damage in the hippocampi of ApoE-/- but not +/+ mice while maintained on the challenge diet. Notably, however, additional significant latent oxidative products were detected during this time. After 31 weeks of dietary challenge, by which time hippocampal oxidative species had doubled, there was an additional 50% in the latent form.Conclusion:This highlights the degree to which ApoE deficiency places hippocampal tissue at risk for oxidative damage. Even a modest dietary deficiency may be sufficient to provoke oxidative damage to hippocampal tissue. These results highlight the combinatorial impact of genetic and dietary deficiencies on oxidative damage to hippocampal tissue.
Highlights
In addition to their well-known deleterious impact on cardiovascular physiology [1], diets high in saturated fat have been implicated in contributing to cognitive decline and neuronal degeneration observed with aging and with diseases such as Alzheimer’s Disease (AD) [2 - 8].Cholesterol and its metabolism may play a role in the pathogenesis of AD
We focused on the hippocampus due to its central and critical role in memory and since it displays some of the earliest impacts on AD [21, 22]
The conversion of latent oxidative species to TBARs revealed significant latent oxidative species in hippocampi of Apolipoprotein E (ApoE)-/- mice maintained on a standard diet
Summary
In addition to their well-known deleterious impact on cardiovascular physiology [1], diets high in saturated fat have been implicated in contributing to cognitive decline and neuronal degeneration observed with aging and with diseases such as Alzheimer’s Disease (AD) [2 - 8].Cholesterol and its metabolism may play a role in the pathogenesis of AD. In addition to their well-known deleterious impact on cardiovascular physiology [1], diets high in saturated fat have been implicated in contributing to cognitive decline and neuronal degeneration observed with aging and with diseases such as Alzheimer’s Disease (AD) [2 - 8]. The incidence of AD is higher in countries with high-fat, high-cholesterol diets [9]. High-fat diets can lead to increases in free radical formation [11] and oxidative stress is a major contributing factor to AD [12, 13]. Endogenous antioxidants such as glutathione help to prevent oxidative damage to tissues [14]. Dietary supplementation with folic acid, vitamin E, and other antioxidants has been shown to slowdown the progress of oxidative stress in brain tissue with subsequent reduction in cognitive deficits in mouse models [11, 14]
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