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=Volume 13 - 2021

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=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- (A) accumulation is unclear.  This study tested the hypothesis that IHT improves learning-memory behavior, diminishes A 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 (n=6), AD+IHT (n=6), and AD+sham-IHT (n=6) groups; 8 untreated wild-type (WT) mice also were studied.  AD+IHT mice alternately breathed 10% O2 for 6 min and room air for 4 min, 10 cycles/day for 21 days; AD+sham-IHT mice breathed room air.  Spatial memory-learning was assessed by Morris water maze.  Cerebrocortical and hippocampal A40 and A42 contents were determined by ELISA, and cerebrocortical erythropoietin and BDNF were analyzed by immunoblotting and ELISA.  The significance of time (12 months 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 A42 contents were greater in 3xTg-AD than WT mice, but neither time nor treatment significantly affected A40 or A42 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 accumulation in 3xTg-AD mice.