Oncotarget

Research Papers: Gerotarget (Focus on Aging):

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

Nady Braidy, Musthafa Mohamed Essa, Anne Poljak, Subash Selvaraju, Samir Al-Adawi, Thamilarasan Manivasagm, Arokiasamy Justin Thenmozhi, Lezanne Ooi, Perminder Sachdev and Gilles J. Guillemin _

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Oncotarget. 2016; 7:64589-64604. https://doi.org/10.18632/oncotarget.10905

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Abstract

Nady Braidy1,*, Musthafa Mohamed Essa2,3,*, Anne Poljak1,4, Subash Selvaraju2,3, Samir Al-Adawi2,4, Thamilarasan Manivasagm5, Arokiasamy Justin Thenmozhi5, Lezanne Ooi6, Perminder Sachdev1,7 and Gilles J. Guillemin8

1 Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia

2 Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al Khoudh, Oman

3 Ageing and Dementia Research Group, Sultan Qaboos University, Al Khoudh, Oman

4 College of Medicine and Health Sciences, Sultan Qaboos University, Al Khoudh, Oman

5 Department of Biochemistry and Biotechnology, Annamalai University, Tamil Nadu, India

6 Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia

7 Neuropsychiatric Institute, The Prince of Wales Hospital, Sydney, Australia

8 Neuroinflammation Group, MND and Neurodegenerative Diseases Research Centre, Macquarie University, NSW, Australia

* These authors have contributed equally to this work

Correspondence to:

Gilles J. Guillemin, email:

Musthafa Mohamed Essa, email:

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

Received: April 04, 2016 Accepted: June 17, 2016 Published: July 28, 2016

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.


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