RT Journal Article
T1 Acute and Chronic Sustained Hypoxia Do Not Substantially Regulate Amyloid-β Peptide Generation In Vivo.
A1 Serrano-Pozo, Alberto
A1 Sanchez-Garcia, Manuel A
A1 Heras-Garvin, Antonio
A1 March-Diaz, Rosana
A1 Navarro, Victoria
A1 Vizuete, Marisa
A1 Lopez-Barneo, Jose
A1 Vitorica, Javier
A1 Pascual, Alberto
K1 Alzheimer Disease
K1 Amyloid beta-Peptides
K1 Aspartic Acid Endopeptidases
K1 Hypoxia-Inducible Factor 1, alpha Subunit
K1 Mice, Transgenic
K1 Real-Time Polymerase Chain Reaction
AB Recent epidemiological evidence has linked hypoxia with the development of Alzheimer disease (AD). A number of in vitro and in vivo studies have reported that hypoxia can induce amyloid-β peptide accumulation through various molecular mechanisms including the up-regulation of the amyloid-β precursor protein, the β-secretase Bace1, or the γγ-secretase complex components, as well as the down-regulation of Aβ-degrading enzymes. To investigate the effects of acute and chronic sustained hypoxia in Aβ generation in vivo. 2-3 month-old C57/Bl6J wild-type mice were exposed to either normoxia (21% O2) or hypoxia (9% O2) for either 4 to 72 h (acute) or 21-30 days (chronic sustained) in a hermetic chamber. Brain mRNA levels of Aβ-related genes were measured by quantitative real-time PCR, whereas levels of Bace1 protein, full length AβPP, and its C-terminal fragments (C99/C88 ratio) were measured by Western blot. In addition, 8 and 14-month-old APP/PS1 transgenic mice were subjected to 9% O2 for 21 days and levels of Aβ40, Aβ42, full length AβPP, and soluble AβPPα (sAβPPα) were measured by ELISA or WB. Hypoxia (either acute or chronic sustained) did not impact the transcription of any of the Aβ-related genes in young wild-type mice. A significant reduction of Bace1 protein level was noted with acute hypoxia for 16 h but did not correlate with an increased level of full length AβPP or a decreased C99/C83 ratio. Chronic sustained hypoxia did not significantly alter the levels of Bace1, full length AβPP or the C99/C83 ratio. Last, chronic sustained hypoxia did not significantly change the levels of Aβ40, Aβ42, full length AβPP, or sAβPPα in either young or aged APP/PS1 mice. Our results argue against a hypoxia-induced shift of AβPP proteolysis from the non-amyloidogenic to the amyloidogenic pathways. We discuss the possible methodological caveats of previous in vivo studies.
PB Public Library of Science
YR 2017
FD 2017-01-18
LK http://hdl.handle.net/10668/10784
UL http://hdl.handle.net/10668/10784
LA en
NO Serrano-Pozo A, Sánchez-García MA, Heras-Garvín A, March-Díaz R, Navarro V, Vizuete M, et al. Acute and Chronic Sustained Hypoxia Do Not Substantially Regulate Amyloid-β Peptide Generation In Vivo. PLoS One. 2017 Jan 18;12(1):e0170345.
DS RISalud
RD Aug 8, 2025