Intermittent hypoxia improves cognition and reduces anxiety‐related behavior in APP/PS1 mice

INTRODUCTION: Although hypoxia can exacerbate symptoms of various neurological disorders, accumulating evidence has indicated that intermittent hypoxia (IH) may exert protective effects against brain diseases. In the present study, we aimed to determine whether exposure to IH exerts beneficial effects in a transgenic murine model of Alzheimer's disease (AD). Because comorbid anxiety is prevalent among patients with AD, we explored the effects of IH on anxiety‐like behaviors and associated factors in APP/PS1 mice. METHODS: APP/PS1 mice were subjected to IH for two weeks. We assessed cognitive performance and anxiety‐related behavior using standard behavioral assessments. Amyloid beta (Aβ) levels in the hippocampus were assessed using immunofluorescence and enzyme‐linked immunosorbent assays (ELISA). We also assessed cell morphology and brain‐derived neurotrophic factor (BDNF) expression in the hippocampus. RESULTS: Exposure to IH significantly increased cognitive performance and decreased anxiety‐related behaviors in APP/PS1 mice. Immunofluorescence and ELISA results revealed that IH pretreatment significantly lowered Aβ levels in the cortex and hippocampus. Morphological studies validated the neuroprotective effect of IH exposure on hippocampal neurogenesis. Molecular studies revealed IH‐enhanced BDNF expression and inhibition of apoptosis‐related protein expression in the hippocampus of APP/PS1 mice. CONCLUSIONS: Our study demonstrates that IH improves cognition and reduces anxiety in a murine model of AD. Thus, further studies are required to determine whether IH can be used as a preventive/adjuvant therapy in patients with AD.