Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Aβ-Oligomers
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 Ca2+ signals at sublethal concentrations and decrease the expression of type-2 ryanodine re...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2016/3456783 |
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| author | Pedro Lobos Barbara Bruna Alex Cordova Pablo Barattini Jose Luis Galáz Tatiana Adasme Cecilia Hidalgo Pablo Muñoz Andrea Paula-Lima |
| author_facet | Pedro Lobos Barbara Bruna Alex Cordova Pablo Barattini Jose Luis Galáz Tatiana Adasme Cecilia Hidalgo Pablo Muñoz Andrea Paula-Lima |
| author_sort | Pedro Lobos |
| collection | DOAJ |
| description | 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 Ca2+ 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. |
| format | Article |
| id | doaj-art-afac18c5045a4f49b04c3054e031acb0 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-afac18c5045a4f49b04c3054e031acb02025-02-03T05:59:18ZengWileyNeural Plasticity2090-59041687-54432016-01-01201610.1155/2016/34567833456783Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Aβ-OligomersPedro Lobos0Barbara Bruna1Alex Cordova2Pablo Barattini3Jose Luis Galáz4Tatiana Adasme5Cecilia Hidalgo6Pablo Muñoz7Andrea Paula-Lima8Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, ChileBiomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, ChileBiomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, ChileBiomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, ChileBiomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, ChileBiomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, ChileBiomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, ChileInterdisciplinary Center for Innovation in Health (CIIS), School of Medicine, University of Valparaíso, 2341369 Valparaíso, ChileBiomedical Neuroscience Institute, Faculty of Medicine, University of Chile, 8380453 Santiago, ChileIncreased 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 Ca2+ 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.http://dx.doi.org/10.1155/2016/3456783 |
| spellingShingle | Pedro Lobos Barbara Bruna Alex Cordova Pablo Barattini Jose Luis Galáz Tatiana Adasme Cecilia Hidalgo Pablo Muñoz Andrea Paula-Lima Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Aβ-Oligomers Neural Plasticity |
| title | Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Aβ-Oligomers |
| title_full | Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Aβ-Oligomers |
| title_fullStr | Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Aβ-Oligomers |
| title_full_unstemmed | Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Aβ-Oligomers |
| title_short | Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Aβ-Oligomers |
| title_sort | astaxanthin protects primary hippocampal neurons against noxious effects of aβ oligomers |
| url | http://dx.doi.org/10.1155/2016/3456783 |
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