Indexed on: 05 Jun '14Published on: 05 Jun '14Published in: Neurochemical Research
Amyloid-β (Aβ)-induced mitochondrial dysfunction has been recognized as a prominent, early event in Alzheimer's disease (AD). Therefore, therapeutics targeted to improve mitochondrial function could be beneficial. Quercetin, a bioflavanoid, has been reported to have potent neuro-protective effects, but its preventive effects on Aβ-induced mitochondrial dysfunction and cognitive impairment have not been well characterised. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two quercetin (either 20 or 40 mg kg(-1) day(-1)) groups, or an Aricept (2 mg kg(-1) day(-1)) group. After 16 weeks of treatment, we observed beneficial effects of quercetin (40 mg kg(-1) day(-1)), including lessening learning and memory deficits, reducing scattered senile plaques, and ameliorating mitochondrial dysfunction, as evidenced by restoration of mitochondrial membrane potential, reactive oxygen species and ATP levels in mitochondria isolated from the hippocampus compared to control. Furthermore, the AMP-activated protein kinase (AMPK) activity significantly increased in the quercetin-treated (40 mg kg(-1) day(-1)) group. These findings suggest that a reduction in plaque burden and mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms by which quercetin improves cognitive functioning in the APPswe/PS1dE9 transgenic mouse model of AD.