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 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.

Haematococcus Pluvialis Extract Promoting the Recovery of Memory Impairment in Alzheimer’s Rats: Anti-Inflammatory and Antiapoptotic Effects

“…In the same line, it has been found that ASTA promoted anti-inflammatory effect by inhibiting the mitochondrial β-oxidation and suppressing the free radicals generation [47]. ASTA, a red-orange carotenoid originates the red of microalgae and other sea organisms, exhibits antioxidant, anti-inflammatory, and antiapoptotic effects [48]. Recently, ASTA was observed to protect neurons in laboratory experiments against chronic and acute neurodegenerative dysfunction, neurological disorders and was proposed as a beneficial strategy to treat neurological diseases [49].…”

Calcium-Involved Action of Phytochemicals: Carotenoids and Monoterpenes in the Brain

“…Incubation of primary hippocampal neurons with AβOs results in significant downregulation of RyR2 mRNA and protein levels; it is possible that these reductions are crucial to the synaptotoxicity induced by β-A. Of note, postmortem samples of patients who died with AD display significantly reduced RyR2 expression at early stages of the disease [40].…”

“…During the prolonged Ca 2+ signaling evoked in Alzheimer's disease, the isoform NFATc4 is activated by CaN, resulting in such abnormalities as neuritic dystrophy and loss of dendritic branching and spines. In vitro research on hippocampal neurons indicates that preincubation with AXT prevents NFATc4 activation by β-A and CaN [40].…”

Serotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?

“…After stimulation with serotype b LPS for 48 h, cell viability was evaluated by the Live/Dead kit (Molecular Probes) as previously described [32]. Briefly, following manufacturer's instructions, the culture medium was Table 1.…”