Grape extract and resveratrol mitigate sleep fragmentation, Aβ accumulation, and abnormal neuronal excitability in a Drosophila model of Alzheimer's disease

Consumption of red wine and grape extracts may offer a range of health benefits, largely attributable to the grapes rich content of vitamins, fiber, and antioxidant compounds, such as polyphenols. To determine if resveratrol (RES) present in grape extracts is responsible for these benefits, we conducted a study on the effects of red grape skin extract (GSKE), seed extract (GSEE), and RES on sleep patterns, amyloid-beta (A{beta}) deposition, neuronal excitability, and lifespan in a Drosophila model expressing A{beta}42. A{beta}42 flies experienced significant sleep fragmentation at night, yet their overall sleep duration was unaffected. Dietary GSKE significantly enhanced sleep duration and mitigated sleep fragmentation in these flies, whereas GSEE only increased the duration of sleep bouts during the day. RES demonstrated a similar effect, albeit to a lesser extent compared to GSKE. All three dietary interventions led to a reduction in A{beta}42 levels and an extension of the lifespan in A{beta}42 flies, with GSEE showing the least pronounced effects. Furthermore, GSEE and RES were able to reverse the hyperexcitability of mushroom body neurons (MBNs) caused by A{beta}42 expression. These results suggest that GSKE and RES are potent promoters of sleep and have the potential to ameliorate sleep disturbances. Additionally, the study highlights that other bioactive component in GSKE, beyond RES, may contribute to its diverse pharmacological activities, which could differ from those of GSEE or RES alone. This underscores the multifaceted nature of grape extracts and their potential therapeutic applications in addressing sleep disorders and neurodegenerative conditions associated with A{beta} deposition.