Astaxanthin protects primary hippocampal neurons against noxious effects of A β-oligomers

Abstract

© 2016 Pedro Lobos et al.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 M ATX for 1.5 h prior to AβOs addition (500 nM). We found that incubation with ATX (≤10 M) for ≤24 h was nontoxic to neurons, evaluated by the live/dead assay. Preincubation with 0