Neuroprotective role of trans-resveratrol in a murine model of familial alzheimer's disease

David Porquet, Christian Griñán-Ferré, Isidre Ferrer, Antoni Camins, Coral Sanfeliu, Jaume Del Valle, Mercè Pallàs

Research output: Contribution to journalArticleResearchpeer-review

96 Citations (Scopus)

Abstract

© 2014-IOS Press and the authors. All rights reserved. The amyloid-β protein precursor/presenilin 1 (AβPP/PS1) mouse model of Alzheimer's disease (AD) has provided robust neuropathological hallmarks of familial AD-like pattern. AD is a neurodegenerative process that causes severe cognitive impairment; it is characterized by the accumulation of amyloid-β (Aβ) and hyperphosphorylated tau forms and by oxidative and inflammatory processes in brain. Currently, efforts are made to understand biochemical pathways because there is no effective therapy for AD. Resveratrol is a polyphenol that induces expression and activation of several neuroprotective pathways involving Sirtuin1 and AMPK. The objective of this work was to assess the effect of oral resveratrol administration on AβPP/PS1 mice. Long-term resveratrol treatment significantly prevented memory loss as measured by the object recognition test. Moreover, resveratrol reduced the amyloid burden and increased mitochondrial complex IV protein levels in mouse brain. These protective effects of resveratrol were mainly mediated by increased activation of Sirtuin 1 and AMPK pathways in mice. However, an increase has been observed in IL1β and TNF gene expression, indicating that resveratrol promoted changes in inflammatory processes, although no changes were detected in other key actors of the oxidative stress pathway. Taken together, our findings suggest that resveratrol is able to reduce the harmful process that occurs in AβPP/PS1 mouse hippocampus, preventing memory loss.
Original languageEnglish
Pages (from-to)1209-1220
JournalJournal of Alzheimer's Disease
Volume42
Issue number4
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • AMPK
  • inflammation
  • mitochondria
  • resveratrol
  • sirtuin 1

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