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

Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that A beta aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila beta-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and A beta burden largely, but not exclusively, via dSir2.

Automated summary

This study found that the natural polyphenolic phytochemical resveratrol (RES) improves sleep and courtship memory in a Drosophila model of Alzheimer's disease (AD) by activating sirtuin 1 (Sirt1/Sir2), and reduces behavioral deficits and A beta burden.