title: Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Aβ-Oligomers.
abstract: Increased reactive oxygen species (ROS) generation and the ensuing oxidative stress contribute to Alzheimer's disease pathology. We reported previously that amyloid-β peptide oligomers (AβOs) produce aberrant Ca(2+) signals at sublethal concentrations and decrease the expression of type-2 ryanodine receptors (RyR2), which are crucial for hippocampal synaptic plasticity and memory. Here, we investigated whether the antioxidant agent astaxanthin (ATX) protects neurons from AβOs-induced excessive mitochondrial ROS generation, NFATc4 activation, and RyR2 mRNA downregulation. To determine mitochondrial H2O2 production or NFATc4 nuclear translocation, neurons were transfected with plasmids coding for HyperMito or NFATc4-eGFP, respectively. Primary hippocampal cultures were incubated with 0.1 μM ATX for 1.5 h prior to AβOs addition (500 nM). We found that incubation with ATX (≤10 μM) for ≤24 h was nontoxic to neurons, evaluated by the live/dead assay. Preincubation with 0.1 μM ATX also prevented the neuronal mitochondrial H2O2 generation induced within minutes of AβOs addition. Longer exposures to AβOs (6 h) promoted NFATc4-eGFP nuclear translocation and decreased RyR2 mRNA levels, evaluated by detection of the eGFP-tagged fluorescent plasmid and qPCR, respectively. Preincubation with 0.1 μM ATX prevented both effects. These results indicate that ATX protects neurons from the noxious effects of AβOs on mitochondrial ROS production, NFATc4 activation, and RyR2 gene expression downregulation.
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile.
authors.forename: Pedro
authors.initials: P
authors.lastname: Lobos
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bruna
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile.
authors.forename: Alex
authors.initials: A
authors.lastname: Cordova
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Barattini
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Galáz
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Adasme
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Institute of Biomedical Sciences and Center for Molecular Studies of the Cell, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hidalgo
authors.affiliation: Interdisciplinary Center for Innovation in Health (CIIS), School of Medicine, University of Valparaíso, 2341369 Valparaíso, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Muñoz
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, 8380492 Santiago, Chile.
authors.forename: Andrea
authors.identifier: 0000-0002-0466-7561
authors.initials: A
authors.lastname: Paula-Lima
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D050778:NFATC Transcription Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C477593:Nfatc4 protein, rat; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D024341:Xanthophylls; C075222:amyloid beta-protein (1-42); C005948:astaxanthine; D006861:Hydrogen Peroxide