Long-term dietary supplementation of pomegranates, figs and dates alleviate neuroinflammation in a transgenic mouse model of Alzheimer's disease.

Musthafa Mohamed Essa,Samir Al-Adawi,Selvaraju Subash,Gilles J Guillemin,Mohammed Akbar,Markus M Heimesaat

doi:10.1371/journal.pone.0120964

Abstract

Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disease with no specific treatment at present. The APPsw/Tg2576 mice exhibit age-related deterioration in memory and learning as well as amyloid-beta (Aβ) accumulation, and this mouse strain is considered an effective model for studying the mechanism of accelerated brain aging and senescence. The present study was aimed to investigate the beneficial effects of dietary supplements pomegranate, figs, or the dates on suppressing inflammatory cytokines in APPsw/Tg2576 mice. Changes in the plasma cytokines and Aβ, ATP, and inflammatory cytokines were investigated in the brain of transgenic mice. Significantly enhanced levels of inflammatory cytokines IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, TNF-α and Eotaxin activity were decreased by administration of the diet supplements containing pomegranates, figs, or dates. In addition, putative delays in the formation of senile plaques, as indicated by a decreasing tendency of brain Aβ1–40 and Aβ1–42 contents, were observed. Thus, novel results mediated by reducing inflammatory cytokines during aging may represent one mechanism by which these supplements exert their beneficial effects against neurodegenerative diseases such as AD.

Highlights

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, characterized by abnormal accumulation of amyloid plaques and neurofibrillary tangles throughout the PLOS ONE | DOI:10.1371/journal.pone.0120964 March 25, 2015Fruits Alleviate Neuroinflammation in Alzheimer's Transgenic Mice cerebrocortical and limbic regions [1]
We have recently reported that the dietary supplementation of pomegranates, figs, or date palm fruits growing in Oman can provide benefits against behavior and oxidative stress related abnormalities in an APPSw2576 transgenic mouse model of AD [71,72,73]
We examined whether dietary supplementation with pomegranates, figs or date palm fruits can attenuate the levels of AD-like Aβ, inflammatory cytokines and ATP in aged APPsw/Tg2576 mice as an in vivo model for AD in comparison to wild type aged mice

Summary

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, characterized by abnormal accumulation of amyloid plaques and neurofibrillary tangles throughout the PLOS ONE | DOI:10.1371/journal.pone.0120964 March 25, 2015Fruits Alleviate Neuroinflammation in Alzheimer's Transgenic Mice cerebrocortical and limbic regions [1]. The neuropathological hallmarks of the disease are amyloid plaques and neurofibrillary tangles (NFT), which progressively accumulate in the brain. These neuropathologies are closely linked with chronic inflammation and neuronal dysfunction. Proinflammatory cytokines, such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF-α), have been reported to be involved in the formation of neuritic plaques in AD [6,7,8]. The Aβ plaques and NFTs accumulated in the brain activate inflammatory cells (i.e. astrocytes and microglia) and tissue levels of pro- and anti-inflammatory mediators, including cytokines and chemokines, are altered. In contrast to the epidemiological studies, patients with a clinical AD syndrome do not benefit from treatment with anti-inflammatory drugs [19]

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