title: Evaluation of Neuropathological Effects of a High-Fat Diet in a Presymptomatic Alzheimer's Disease Stage in APP/PS1 Mice.
abstract: Alzheimer's disease (AD) is currently an incurable aging-related neurodegenerative disorder. Recent studies give support to the hypotheses that AD should be considered as a metabolic disease. The present study aimed to explore the relationship between hippocampal neuropathological amyloid-β (Aβ) plaque formation and obesity at an early presymptomatic disease stage (3 months of age). For this purpose, we used APPswe/PS1dE9 (APP/PS1) transgenic mice, fed with a high-fat diet (HFD) in order to investigate the potential molecular mechanisms involved in both disorders. The results showed that the hippocampus from APP/PS1 mice fed with a HFD had an early significant decrease in Aβ signaling pathway specifically in the insulin degrading enzyme protein levels, an enzyme involved in (Aβ) metabolism, and α-secretase. These changes were accompanied by a significant increase in the occurrence of plaques in the hippocampus of these mice. Furthermore, APP/PS1 mice showed a significant hippocampal decrease in PGC-1α levels, a cofactor involved in mitochondrial biogenesis. However, HFD does not provoke changes in neither insulin receptors gene expression nor enzymes involved in the signaling pathway. Moreover, there are no changes in any enzymes (kinases) involved in tau phosphorylation, such as CDK5, and neither in brain oxidative stress production. These results suggest that early changes in brains of APP/PS1 mice fed with a HFD are mediated by an increase in Aβ1 ‒ 42, which induces a decrease in PKA levels and alterations in the p-CREB/ NMDA2B /PGC1-α pathway, favoring early AD neuropathology in mice.
authors: Unitat de Farmacologia i Farmacognòsia, Institut de Neurociencias, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.|Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors: Miren
authors: M
authors: Ettcheto
authors: Unitat de Farmacologia i Farmacognòsia, Institut de Neurociencias, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.|Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors: Dmitry
authors: D
authors: Petrov
authors: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus (Tarragona), Spain.|Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors: Ignacio
authors: I
authors: Pedrós
authors: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
authors: Norma
authors: N
authors: Alva
authors: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
authors: Teresa
authors: T
authors: Carbonell
authors: Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, CIBO, IMSS, México.|Laboratorio de Regeneración y Desarrollo Neural, Instituto de Neurobiología, Departamento de Biología Celular y Molecular, CUCBA, México.
authors: Carlos
authors: C
authors: Beas-Zarate
authors: Unitat de Farmacologia i Farmacognòsia, Institut de Neurociencias, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.|Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors: Merce
authors: M
authors: Pallas
authors: Departament de Biologia Cellular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
authors: Carme
authors: C
authors: Auladell
authors: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus (Tarragona), Spain.|Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors: Jaume
authors: J
authors: Folch
authors: Unitat de Farmacologia i Farmacognòsia, Institut de Neurociencias, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.|Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors: Antoni
authors: A
authors: Camins
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D062706:Prodromal Symptoms; D021641:Recognition, Psychology / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007328:Insulin; C558298:Mapt protein, mouse; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D002784:Cholesterol; D005947:Glucose
keywords: APPSwe/PS1dE9; Alzheimer’s disease; hippocampus; insulin receptor; mitochondria; tau