Long-term (15 mo) dietary supplementation with pomegranates from Oman attenuates cognitive and behavioral deficits in a transgenic mice model of Alzheimer's disease

Abstract

ObjectiveTransgenic (Tg) mice, which possess an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid β (Aβ) deposition in the brain, and severe memory and behavioral deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving quality of life in individuals with AD. The aim of this study was to investigate the effect of dietary supplementation of Omani pomegranate extract on memory, anxiety, and learning skills in an AD mouse model possessing the double Swedish APP mutation (APPsw/Tg2576). MethodsThe experimental groups of APP-Tg mice from the age of 4 mo were fed a custom mixed diet (pellets) containing 4% pomegranate. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4 to 5 mo and 18 to 19 mo using the Morris water maze test, rotarod performance test, elevated plus-maze test, and open field test. ResultsAPPsw/Tg2576 mice that were fed a standard chow diet without pomegranates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability, and motor coordination compared with the wild-type mice on the same diet, at the age of 18 to 19 mo. In contrast, APPsw/Tg2576 mice that were fed a diet containing 4% pomegranates showed significant improvements in memory, learning, locomotor function, as well as reduction in anxiety, compared with APPsw/Tg2576 mice fed the standard chow diet. ConclusionOur results suggest that dietary supplementation with pomegranates may slow the progression of cognitive and behavioral impairments in AD.