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

Journal Article


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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


  •   Braidy, Nady (external author)
  •   Essa, Musthafa (external author)
  •   Poljak, Anne (external author)
  •   Selvaraju, Subash (external author)
  •   Al-Adawi, Samir (external author)
  •   Manivasagm, Thamilarasan (external author)
  •   Thenmozhi, Arokiasamy (external author)
  •   Ooi, Lezanne
  •   Sachdev, Perminder (external author)
  •   Guillemin, Gilles (external author)

Publication Date


  • 2016

Citation


  • Braidy, N., Essa, M. Mohammed., Poljak, A., Selvaraju, S., Al-Adawi, S., Manivasagm, T., Thenmozhi, A. Justin., Ooi, L., Sachdev, P. & Guillemin, G. J. (2016). Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease. Oncotarget, 7 (40), 64589-64604.

Scopus Eid


  • 2-s2.0-84994097012

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1959&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/934

Has Global Citation Frequency


Number Of Pages


  • 15

Start Page


  • 64589

End Page


  • 64604

Volume


  • 7

Issue


  • 40

Place Of Publication


  • United States

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


  •   Braidy, Nady (external author)
  •   Essa, Musthafa (external author)
  •   Poljak, Anne (external author)
  •   Selvaraju, Subash (external author)
  •   Al-Adawi, Samir (external author)
  •   Manivasagm, Thamilarasan (external author)
  •   Thenmozhi, Arokiasamy (external author)
  •   Ooi, Lezanne
  •   Sachdev, Perminder (external author)
  •   Guillemin, Gilles (external author)

Publication Date


  • 2016

Citation


  • Braidy, N., Essa, M. Mohammed., Poljak, A., Selvaraju, S., Al-Adawi, S., Manivasagm, T., Thenmozhi, A. Justin., Ooi, L., Sachdev, P. & Guillemin, G. J. (2016). Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease. Oncotarget, 7 (40), 64589-64604.

Scopus Eid


  • 2-s2.0-84994097012

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1959&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/934

Has Global Citation Frequency


Number Of Pages


  • 15

Start Page


  • 64589

End Page


  • 64604

Volume


  • 7

Issue


  • 40

Place Of Publication


  • United States