AUTHOR=Ryou Myoung-Gwi , Chen Xiaoan , Cai Ming , Wang Hong , Jung Marianna E. , Metzger Daniel B. , Mallet Robert T. , Shi Xiangrong 

TITLE=Intermittent Hypoxia Training Prevents Deficient Learning-Memory Behavior in Mice Modeling Alzheimer's Disease: A Pilot Study

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.674688

DOI=10.3389/fnagi.2021.674688

ISSN=1663-4365

ABSTRACT=<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-β (Aβ) accumulation is unclear. This study tested the hypothesis that IHT improves learning-memory behavior, diminishes Aβ 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 (<italic>n</italic> = 6), AD+IHT (<italic>n</italic> = 6), and AD+sham-IHT (<italic>n</italic> = 6) groups; 8 untreated wild-type (WT) mice also were studied. AD+IHT mice alternately breathed 10% O<sub>2</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 Aβ<sub>40</sub> and Aβ<sub>42</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 (−1.6 ± 1.8 m) differed from that after sham-IHT (+5.8 ± 2.6 m). Cerebrocortical and hippocampal Aβ<sub>42</sub> contents were greater in 3xTg-AD than WT mice, but neither time nor treatment significantly affected Aβ<sub>40</sub> or Aβ<sub>42</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 Aβ accumulation in 3xTg-AD mice.</p>