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

Oncotarget. 2016 Oct 4;7(40):64589-64604. doi: 10.18632/oncotarget.10905.

Abstract

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.

Keywords: Gerotarget; amyloid beta protein; amyloid precursor protein; inflammation; pomegranates; synapse.

MeSH terms

  • Alzheimer Disease / diet therapy*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Brain / immunology*
  • Brain / pathology
  • Diet
  • Disease Models, Animal
  • Disks Large Homolog 4 Protein / metabolism
  • Electrical Synapses / metabolism*
  • Female
  • Humans
  • Inflammation / diet therapy*
  • Inflammation / metabolism
  • Lythraceae*
  • Mice
  • Mice, Transgenic
  • Munc18 Proteins / metabolism
  • Neuronal Plasticity / drug effects
  • Neuroprotective Agents
  • Oncogene Protein v-akt / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Plant Extracts / therapeutic use*
  • Plaque, Amyloid / metabolism*
  • Signal Transduction / drug effects
  • Synaptosomal-Associated Protein 25 / metabolism
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • Disks Large Homolog 4 Protein
  • Munc18 Proteins
  • Neuroprotective Agents
  • Plant Extracts
  • Synaptosomal-Associated Protein 25
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Oncogene Protein v-akt