title: Neuroprotective role of trans-resveratrol in a murine model of familial Alzheimer's disease.
abstract: 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.
authors.affiliation: Secció de Farmacologia, Departament Farmacologia i Química Terapéutica, Facultat de Farmácia, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: David
authors.initials: D
authors.lastname: Porquet
authors.affiliation: Secció de Farmacologia, Departament Farmacologia i Química Terapéutica, Facultat de Farmácia, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Griñán-Ferré
authors.affiliation: Institut de Neuropatologia de l'Hospital Universitari de Bellvitge, Institut d'Investigació Biomédica de Bellvitge, Universitat de Barcelona, Bellvitge, Spain Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Secció de Farmacologia, Departament Farmacologia i Química Terapéutica, Facultat de Farmácia, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.affiliation: Institut d'Investigacions Biomèdiques de Barcelona, CSIC, IDIBAPS, Barcelona, Spain.
authors.forename: Coral
authors.initials: C
authors.lastname: Sanfeliu
authors.affiliation: Secció de Farmacologia, Departament Farmacologia i Química Terapéutica, Facultat de Farmácia, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain Grup de Neuroplasticitat i Regeneració, Institut de Neurociències i Departament de Biologia Cellular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Bellaterra, Spain Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Del Valle
authors.affiliation: Secció de Farmacologia, Departament Farmacologia i Química Terapéutica, Facultat de Farmácia, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Pallàs
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D008569:Memory Disorders / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; C508853:PSEN1 protein, human; D053764:Presenilin-1; D013267:Stilbenes; D000077185:Resveratrol
keywords: AMPK; inflammation; mitochondria; resveratrol; sirtuin 1