Resveratrol increases cerebral glycogen synthase kinase phosphorylation as well as protein levels of drebrin and transthyretin in mice: an exploratory study

Alzheimer's disease (AD) is characterized by intraneuronal beta-amyloid plaques and hyperphosphorylated tau, leading to neuronal cell death and progressive memory losses. This exploratory work investigates if dietary resveratrol, previously shown to have broad antiaging effects and improve AD pathology in vivo, leads to neuroprotective changes in specific protein targets in the mouse brain. Both wild-type and APP/PS1 mice, a transgenic AD mouse model, received control AIN-93G diet or AIN-93G supplemented with resveratrol. Pathology parameters and AD risk were assessed via measurements on plaque burden, levels of phosphorylated glycogen synthase kinase 3-beta (GSK3-beta), tau, transthyretin and drebrin. Dietary resveratrol treatment did not decrease plaque burden in APP/PS1 mice. However, resveratrol-fed mice demonstrated increases in GSK3-beta phosphorylation, a 3.8-fold increase in protein levels of transthyretin, and a 2.2-fold increase in drebrin. This study broadens our understanding of specific mechanisms and targets whereby resveratrol provides neuroprotection.