title: Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease.
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.
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Nady
authors.initials: N
authors.lastname: Braidy
authors.affiliation: Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al Khoudh, Oman.|Ageing and Dementia Research Group, Sultan Qaboos University, Al Khoudh, Oman.
authors.forename: Musthafa Mohamed
authors.initials: MM
authors.lastname: Essa
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.|College of Medicine and Health Sciences, Sultan Qaboos University, Al Khoudh, Oman.
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.affiliation: Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al Khoudh, Oman.|Ageing and Dementia Research Group, Sultan Qaboos University, Al Khoudh, Oman.
authors.forename: Subash
authors.initials: S
authors.lastname: Selvaraju
authors.affiliation: Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al Khoudh, Oman.|College of Medicine and Health Sciences, Sultan Qaboos University, Al Khoudh, Oman.
authors.forename: Samir
authors.initials: S
authors.lastname: Al-Adawi
authors.affiliation: Department of Biochemistry and Biotechnology, Annamalai University, Tamil Nadu, India.
authors.forename: Thamilarasan
authors.initials: T
authors.lastname: Manivasagm
authors.affiliation: Department of Biochemistry and Biotechnology, Annamalai University, Tamil Nadu, India.
authors.forename: Arokiasamy Justin
authors.initials: AJ
authors.lastname: Thenmozhi
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia.
authors.forename: Lezanne
authors.initials: L
authors.lastname: Ooi
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.|Neuropsychiatric Institute, The Prince of Wales Hospital, Sydney, Australia.
authors.forename: Perminder
authors.initials: P
authors.lastname: Sachdev
authors.affiliation: Neuroinflammation Group, MND and Neurodegenerative Diseases Research Centre, Macquarie University, NSW, Australia.
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
mesh_terms: D000544:Alzheimer Disease / Q000178:diet therapy* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein / Q000378:metabolism; D054351:Electrical Synapses / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000178:diet therapy* / Q000378:metabolism; D029561:Lythraceae; D051379:Mice; D008822:Mice, Transgenic; D051938:Munc18 Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D018696:Neuroprotective Agents; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000627:therapeutic use*; D058225:Plaque, Amyloid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D000076122:Disks Large Homolog 4 Protein; D051938:Munc18 Proteins; D018696:Neuroprotective Agents; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D010936:Plant Extracts; D050825:Synaptosomal-Associated Protein 25; D058570:TOR Serine-Threonine Kinases; C546843:mTOR protein, mouse
keywords: Gerotarget; amyloid beta protein; amyloid precursor protein; inflammation; pomegranates; synapse