Articulo
Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of A beta-Oligomers
Fecha
2016Registro en:
1150736
WOS:000373588100001
Institución
Resumen
Increased reactive oxygen species (ROS) generation and the ensuing oxidative stress contribute to Alzheimer's disease pathology. We reported previously that amyloid-beta peptide oligomers (A beta Os) 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 A beta Os-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 mu M ATX for 1.5 h prior to A beta Os addition (500 nM). We found that incubation with ATX (<= 10 mu M) for <= 24 h was nontoxic to neurons, evaluated by the live/dead assay. Preincubation with 0.1 mu M ATX also prevented the neuronal mitochondrial H2O2 generation induced within minutes of A beta Os addition. Longer exposures to A beta Os (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 mu M ATX prevented both effects. These results indicate that ATX protects neurons from the noxious effects of A beta Os on mitochondrial ROS production, NFATc4 activation, and RyR2 gene expression downregulation.