title: Quercetin Exerts Differential Neuroprotective Effects Against H2O2and Aβ Aggregates in Hippocampal Neurons: the Role of Mitochondria.
abstract: Amyloid-β peptide (Aβ) is one of the major players in the pathogenesis of Alzheimer's disease (AD). Despite numerous studies, the mechanisms by which Aβ induces neurodegeneration are not completely understood. Oxidative stress is considered a major contributor to the pathogenesis of AD, and accumulating evidence indicates that high levels of reactive oxygen species (ROS) are involved in Aβ-induced neurodegeneration. Moreover, Aβ can induce the deregulation of calcium homeostasis, which also affects mitochondrial function and triggers neuronal cell death. In the present study, we analyzed the effects of quercetin, a plant flavonoid with antioxidant properties, on oxidative stress- and Aβ-induced degeneration. Our results indicate that quercetin efficiently protected against H2O2-induced neuronal toxicity; however, this protection was only partial in rat hippocampal neurons that were treated with Aβ. Treatment with quercetin decreased ROS levels, recovered the normal morphology of mitochondria, and prevented mitochondrial dysfunction in neurons that were treated with H2O2. By contrast, quercetin treatment partially rescued hippocampal neurons from Aβ-induced mitochondrial injury. Most importantly, quercetin treatment prevented the toxic effects that are induced by H2O2in hippocampal neurons and, to a lesser extent, the Aβ-induced toxicity that is associated with the superoxide anion, which is a precursor of ROS production in mitochondria. Collectively, these results indicate that quercetin exerts differential effects on the prevention of H2O2- and Aβ-induced neurotoxicity in hippocampal neurons and may be a powerful tool for dissecting the molecular mechanisms underlying Aβ neurotoxicity.
authors: Centro de Envejecimiento y Regeneración (CARE UC), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile.
authors: Juan A
authors: JA
authors: Godoy
authors: Centro de Envejecimiento y Regeneración (CARE UC), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile.
authors: Carolina B
authors: CB
authors: Lindsay
authors: Laboratory of Neurodegenerative Diseases, Centro de Investigación Biomédica, Universidad Autónoma de Chile, Santiago de Chile, Chile.
authors: Rodrigo A
authors: RA
authors: Quintanilla
authors: Laboratorio de Función y Patología Neuronal, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile.
authors: Francisco J
authors: FJ
authors: Carvajal
authors: Laboratorio de Función y Patología Neuronal, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile. wcerpa@bio.puc.cl.
authors: Waldo
authors: W
authors: Cerpa
authors: Centro de Envejecimiento y Regeneración (CARE UC), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile. ninestrosa@bio.puc.cl.|Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia. ninestrosa@bio.puc.cl.|Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile. ninestrosa@bio.puc.cl.
authors: Nibaldo C
authors: NC
authors: Inestrosa
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D006624:Hippocampus / Q000473:pathology*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D066329:Protein Aggregates; D011794:Quercetin / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D066329:Protein Aggregates; D017382:Reactive Oxygen Species; D011794:Quercetin; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase
keywords: Alzheimer’s disease; Oxidative stress; Quercetin; Sod −/+ mice; Αβ aggregates