Resveratrol and Sir2 Reverse Sleep and Memory Defects Induced by Amyloid Precursor Protein

In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in aDrosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase ofDrosophila Sir2 (dSir2) by RES supplementation for up to 17 days inAPP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits inAPP flies. We further demonstrated that dSir2 acts as a sleep promotor inDrosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 indSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down inAPP flies. Finally, we showed that A β aggregates inAPP flies were reduced by RES and dSir2, probablyvia inhibitingDrosophilaβ-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively,via dSir2.
Source: Neuroscience Bulletin - Category: Neuroscience Source Type: research