{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:18:07Z","timestamp":1791955087617,"version":"4.3.4"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>In mouse models of Alzheimer's disease (AD), normobaric intermittent hypoxia training (IHT) can preserve neurobehavioral function when applied before deficits develop, but IHT's effectiveness after onset of amyloid-\u03b2 (A\u03b2) accumulation is unclear. This study tested the hypothesis that IHT improves learning-memory behavior, diminishes A\u03b2 accumulation in cerebral cortex and hippocampus, and enhances cerebrocortical contents of the neuroprotective trophic factors erythropoietin and brain-derived neurotrophic factor (BDNF) in mice manifesting AD traits. Twelve-month-old female 3xTg-AD mice were assigned to untreated 3xTg-AD (<jats:italic>n<\/jats:italic> = 6), AD+IHT (<jats:italic>n<\/jats:italic> = 6), and AD+sham-IHT (<jats:italic>n<\/jats:italic> = 6) groups; 8 untreated wild-type (WT) mice also were studied. AD+IHT mice alternately breathed 10% O<jats:sub>2<\/jats:sub> for 6 min and room air for 4 min, 10 cycles\/day for 21 days; AD+sham-IHT mice breathed room air. Spatial learning-memory was assessed by Morris water maze. Cerebrocortical and hippocampal A\u03b2<jats:sub>40<\/jats:sub> and A\u03b2<jats:sub>42<\/jats:sub> contents were determined by ELISA, and cerebrocortical erythropoietin and BDNF were analyzed by immunoblotting and ELISA. The significance of time (12 vs. 12 months + 21 days) and treatment (IHT vs. sham-IHT) was evaluated by two-factor ANOVA. The change in swimming distance to find the water maze platform after 21 d IHT (\u22121.6 \u00b1 1.8 m) differed from that after sham-IHT (+5.8 \u00b1 2.6 m). Cerebrocortical and hippocampal A\u03b2<jats:sub>42<\/jats:sub> contents were greater in 3xTg-AD than WT mice, but neither time nor treatment significantly affected A\u03b2<jats:sub>40<\/jats:sub> or A\u03b2<jats:sub>42<\/jats:sub> contents in the 3xTg-AD mice. Cerebrocortical erythropoietin and BDNF contents increased appreciably after IHT as compared to untreated 3xTg-AD and AD+sham-IHT mice. In conclusion, moderate, normobaric IHT prevented spatial learning-memory decline and restored cerebrocortical erythropoietin and BDNF contents despite ongoing A\u03b2 accumulation in 3xTg-AD mice.<\/jats:p>","DOI":"10.3389\/fnagi.2021.674688","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T15:31:16Z","timestamp":1625153476000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Intermittent Hypoxia Training Prevents Deficient Learning-Memory Behavior in Mice Modeling Alzheimer's Disease: A Pilot Study"],"prefix":"10.3389","volume":"13","author":[{"given":"Myoung-Gwi","family":"Ryou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna E.","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Metzger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Mallet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangrong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0024-20.2020","article-title":"A HIF1a-dependent pro-oxidant state disrupts synaptic plasticity and impairs spatial memory in response to intermittent hypoxia","author":"Arias-Cavieres","year":"2020","journal-title":"eNeuro"},{"key":"B2","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/0968-0004(94)90173-2","article-title":"Role of the beta-amyloid precursor protein in Alzheimer's disease","volume":"19","author":"Ashall","year":"1994","journal-title":"Trends Biochem. 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