Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease

• DOI: 10.18632/oncotarget.10905
• Publication Date: 2016-07-29T02:53:49Z
• Authors: Nady Braidy; Musthafa Mohamed ...; Anne Poljak; Subash Selvaraju; Samir Al-Adawi; Thamilarasan Mani...; Arokiasamy Justin...; Lezanne Ooi; Perminder Sachdev; Gilles J. Guillemin
• Keywords: Aging; 32 Biomedical and Clinical Sciences; amyloid precursor protein; Neurodegenerative; Alzheimer's Disease; Transgenic; Amyloid beta-Protein Precursor; Mice; Phosphatidylinositol 3-Kinases; Research Paper: Gerotarget (Focus on Aging); 0302 clinical medicine; synapse; Medicine and Health Sciences; 2.1 Biological and endogenous factors; Plaque; Lythraceae; Neuronal Plasticity; Gerotarget; TOR Serine-Threonine Kinases; Brain; 3. Good health; Oncogene Protein v-akt; Neuroprotective Agents; Neurological; Female; Disks Large Homolog 4 Protein; Signal Transduction; Amyloid; 571; Synaptosomal-Associated Protein 25; pomegranates; 1.1 Normal biological development and functioning; 610; Mice, Transgenic; 03 medical and health sciences; anzsrc-for: 32 Biomedical and Clinical Sciences; Electrical Synapses; Munc18 Proteins; Alzheimer Disease; Complementary and Integrative Health; Acquired Cognitive Impairment; Animals; Humans; Nutrition; anzsrc-for: 3211 Oncology and Carcinogenesis; Inflammation; Animal; Plant Extracts; Neurosciences; Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD); 3211 Oncology and Carcinogenesis; Brain Disorders; Diet; Disease Models, Animal; amyloid beta protein; Dietary Supplements; Disease Models; Dementia

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by extracellular plaques containing abnormal Amyloid Beta (Aβ) aggregates, intracellular neurofibrillary tangles containing hyperphosphorylated tau protein, microglia-dominated neuroinflammation, and impairments in synaptic plasticity underlying cognitive deficits. Therapeutic strategies for the treatment of AD are currently limited. In this study, we investigated the effects of dietary supplementation of 4% pomegranate extract to a standard chow diet on neuroinflammation, and synaptic plasticity in APPsw/Tg2576 mice brain. Treatment with a custom mixed diet (pellets) containing 4% pomegranate for 15 months ameliorated the loss of synaptic structure proteins, namely PSD-95, Munc18-1, and SNAP25, synaptophysin, phosphorylation of Calcium/Calmodulin Dependent Protein Kinase IIα (p-CaMKIIα/ CaMKIIα), and phosphorylation of Cyclic AMP-Response Element Binding Protein (pCREB/CREB), inhibited neuroinflammatory activity, and enhanced autophagy, and activation of the phophoinositide-3-kinase-Akt-mammalian target of rapamycin signaling pathway. These neuroprotective effects were associated with reduced β-site cleavage of Amyloid Precursor Protein in APPsw/Tg2576 mice. Therefore, long-term supplementation with pomegranates can attenuate AD pathology by reducing inflammation, and altering APP-dependent processes.