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Correction: Acute and Chronic Sustained Hypoxia Do Not Substantially Regulate Amyloid-β Peptide Generation In Vivo

  • The PLOS ONE Staff

There are several errors throughout the paper. The publisher apologizes for these errors. The figure legend for Fig 1 is incorrect. Please see the Fig 1 and the correct figure legend below.

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Fig 1. Characterization of hypoxia treatment protocols used in this study.

(A) Schematic of acute (top) and chronic sustained (bottom) hypoxia treatment protocol used in this study. White arrowheads represent reoxygenation (21% O2) for 24 h. (B) Top, WB for HIF1α in brain extracts from 2–3 month-old wild-type mice subjected to AH (9% O2) for either 4 h or 16 h. Bottom, quantification of HIF1α WB. p < 0.05; Kruskal-Wallis ANOVA with Dunn’s multiple comparison test, n = 3 per group. (C) Vegfa mRNA levels measured by qRT-PCR in 2–3 month-old wild-type mice in normoxia and after AH (9% O2) for 16 h. Note the ~5-fold up-regulation of Vegfa expression caused by AH, which was reverted by 24 h reoxygenation. * p < 0.05; Kruskal-Wallis ANOVA with Dunn’s multiple comparison test, n = 4 per group. (D) Vegfa mRNA levels measured by qRT-PCR in 2–3 month-old wild-type mice in normoxia and after CSH (21 days, 9% O2), with and without reoxygenation (24 h, 21% O2). Note the ~2-fold up-regulation caused by CSH, which was not reverted by 24 h reoxygenation.* p < 0.05; Kruskal-Wallis ANOVA with Dunn’s multiple comparison test, n = 4 per group. (E) Vegf protein levels were measured by ELISA in 2–3 month-old wild-type mice subjected to either CSH (30 days, 9% O2) or normoxia (30 days, 21% O2 within the same chamber). A non-significant ~3-fold increase was observed in CSH compared to normoxia. Mann-Whitney U test, n = 4 per group. (F) Hematocrit of 14-month-old APP/PS1 mice subjected to CSH (21 days, 9% O2) or normoxia (21 days, 21% O2 within the same chamber). CSH was associated with a ~2-fold increase. p = 0.003; Mann-Whitney U test, n = 4 per group. Bars ± error bars represent mean ± s.e.m. HIF1α = hypoxia inducible factor 1 alpha; α-tub = alpha-tubulin; Vegf = vascular endothelial growth factor.

https://doi.org/10.1371/journal.pone.0181510.g001

The Table 2 legend is incorrectly incorporated into the body of the manuscript. Additionally, the order of rows for Table 2 is incorrect. The correct order of columns from left to right should be: Author / year, Model, Hypoxia method, Hypoxia level, Hypoxia duration, CO2 level, Results (APP, BACE, γ-secretase, Aβ, Neprilysin, Tau, Synapses, Behavior). Please see the correct Table 2 and Table 2 legend below.

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Table 2. Literature review on regulation of Aβ Metabolism by hypoxia.

Results of a search in the US National Library of Medicine of the National Institutes of Health (http://www.ncbi.nlm.nih.gov/pubmed/) using the combination of keywords “hypoxia AND Alzheimer”. Both in vitro and in vivo studies were included. In vitro studies used either exposure to a low O2 level within the cell incubator or treatment with hypoxia mimics (i.e. NiCl2 or DMOG), and either cell lines stably expressing an AβPP construct, (i.e. the 695 amino acid wild-type form or the Swedish mutation) or primary rat cortical cultures, both neuronal and astrocytic. Note: Articles were excluded if: 1) they exclusively described the effects of hypoxia on tau phosphorylation/pathology or some other aspect of AD pathophysiology (i.e. mitochondrial dysfunction) without addressing its effects on Aβ; 2) they used a paradigm other than pure hypoxia (i.e. ischemia, hypocapnia, oxygen and glucose deprivation, oxidative stress), and 3) they were written in a language different from English.

Abbreviations: ↓: significant decrease; ↑: significant increase; =: no significant change; d: days; EM: electron microscopy; F: female; FA: formic acid; h: hours; hu: human; M: male; Mme = neprilysin mRNA; mo: month; mu: murine; MWM: Morris water maze (↓ indicates worse performance); NA: not available; NFT: neurofibrillary tangle; OF: open field; syn: synaptophysin; TST: tail suspension test (↓ indicates worse performance). Note: mRNAs are expressed in Italics, whereas proteins are Capitalized.

https://doi.org/10.1371/journal.pone.0181510.t001

Reference

  1. 1. Serrano-Pozo A, Sánchez-García MA, Heras-Garvín A, March-Díaz R, Navarro V, Vizuete M, et al. (2017) Acute and Chronic Sustained Hypoxia Do Not Substantially Regulate Amyloid-β Peptide Generation In Vivo. PLoS ONE 12(1): e0170345. pmid:28099462