To date there are no mouse lines that model late-onset/age-related Alzheimer's disease (AD), the feature which accounts for the vast majority of cases. The senescence-accelerated mouse (SAMP8), a model of aging, displays many features that are known to occur early in the pathogenesis of AD. Therefore, SAMP8 mice may be an excellent model for studying the earliest neurodegenerative changes associated with AD and determine the effectiveness of therapies. Recent studies have implicated resveratrol and pterostilbene, a resveratrol derivative, in the protection against age-related diseases, such as cancer, diabetes, and neurodegenerative diseases in addition to age-related conditions such as cognitive decline, a risk factor for AD. The purpose of this study was to compare the effectiveness of physiologically relevant doses of resveratrol and pterostilbene on age-related cognitive changes and signaling pathways associated with AD. Our findings demonstrate that both resveratrol and pterostilbene, at equivalent doses, were able to upregulate SIRT1. However, pterostilbene and resveratrol differentially modulated stress/survival pathways and pterostilbsene was more effective than resveratrol at modulating cognitive function and oxidative stress levels. These findings indicate that pterostilbene is more potent both at a behavior and cellular level. Increased lipophilicity by the substitution of hydroxy with methoxy group in pterostibene may result in better bioavailability and, therefore, increased biological activity than an equivalent dose of resveratrol.

Modulation of cognition and stress/survival signaling pathways by resveratrol and pterostilbene in age-accelerated SAMP8 mice

239th National Meeting (2010)

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