Erratum: The Antioxidant N-Acetylcysteine Prevents the Mitochondrial Fragmentation Induced by Soluble Amyloid-F Peptide Oligomers

Background: Soluble amyloid-F peptide oligomers (AFOs), which are centrally involved in the pathogenesis of Alzheimer’s disease, trigger Ca2+ influx through N-methyl-D-aspartate receptors and stimulate reactive oxygen species generation in primary hippocampal neurons. We have previously reported that AFOs promote Ca2+ release mediated by ryanodine receptors (RyR), which in turn triggers mitochondrial fragmentation. We have also reported that the antioxidant N-acetylcysteine (NAC) prevents AFOs-induced Ca2+ signal generation. Objectives: To determine if RyR-mediated Ca2+ release activated by the specific agonist 4-chloro-m-cresol (4-CMC) induces fragmentation of the mitochondrial network, and to ascertain if NAC prevents the mitochondrial fragmentation induced by AFOs and/or 4-CMC. Methods: Mature primary rat hippocampal neurons were incubated for 24 h with sublethal concentrations of AFOs (500 nM) or for 1–3 h with 4-CMC (0.5–1 mM), w10 mM NAC. Mitochondrial morphology was assessed by confocal microscopy of fixed neurons stained with anti-mHsp70. Intracellular Ca2+ levels were determined by time series microscopy of neurons preloaded with Fluo-4 AM. Results: Preincubation of neurons for 30 min with NAC prevented the mitochondrial fragmentation induced by AFOs or 4-CMC. In addition, we confirmed that preincubation with NAC abolished the stimulation of RyR-mediated Ca2+ release induced by AFOs or 4-CMC. Conclusion: The present results strongly suggest that the general antioxidant NAC prevents AFO-induced mitochondrial fragmentation by preventing RyR-mediated Ca2+-induced Ca2+ release. Copyright i 2012 S. Karger AG, Basel