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, Gilles J. Guillemin

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)64589-64604
Number of pages16
JournalOncotarget
Volume7
Issue number40
DOIs
Publication statusPublished - 2016

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Transgenic Mice
Alzheimer Disease
Punicaceae
Neuronal Plasticity
Phosphorylation
Diet
tau Proteins
Cyclic AMP Response Element-Binding Protein
Calcium-Calmodulin-Dependent Protein Kinases
Synaptophysin
Neurofibrillary Tangles
Amyloid beta-Protein Precursor
Autophagy
Microglia
Neuroprotective Agents
Sirolimus
Dietary Supplements
Amyloid
Neurodegenerative Diseases

Keywords

  • Amyloid beta protein
  • Amyloid precursor protein
  • Gerotarget
  • Inflammation
  • pomegranates
  • Synapse

ASJC Scopus subject areas

  • Oncology

Cite this

Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease. / Braidy, Nady; Essa, Musthafa Mohamed; Poljak, Anne; Selvaraju, Subash; Al-Adawi, Samir; Manivasagm, Thamilarasan; Thenmozhi, Arokiasamy Justin; Ooi, Lezanne; Sachdev, Perminder; Guillemin, Gilles J.

In: Oncotarget, Vol. 7, No. 40, 2016, p. 64589-64604.

Research output: Contribution to journalArticle

Braidy, N, Essa, MM, Poljak, A, Selvaraju, S, Al-Adawi, S, Manivasagm, T, Thenmozhi, AJ, Ooi, L, Sachdev, P & Guillemin, GJ 2016, 'Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease', Oncotarget, vol. 7, no. 40, pp. 64589-64604. https://doi.org/10.18632/oncotarget.10905
Braidy, Nady ; Essa, Musthafa Mohamed ; Poljak, Anne ; Selvaraju, Subash ; Al-Adawi, Samir ; Manivasagm, Thamilarasan ; Thenmozhi, Arokiasamy Justin ; Ooi, Lezanne ; Sachdev, Perminder ; Guillemin, Gilles J. / Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease. In: Oncotarget. 2016 ; Vol. 7, No. 40. pp. 64589-64604.
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