Chronic Intermittent Hypoxia Induces Cognitive Impairment in Alzheimer's Disease Mouse Model Via Postsynaptic Mechanisms

Overview

Journal Sleep Breath

Publisher Springer

Date 2024 Jan 24

PMID 38267641

Authors

Juan Li

Jingying Ye

Affiliations

Soon will be listed here.

Abstract

Purpose: Obstructive sleep apnea (OSA) is highly comorbid with Alzheimer's disease (AD) and may represent a risk factor for inducing or accelerating cognitive impairment in AD. Chronic intermittent hypoxia (CIH) has been considered to be a predictor of developing cognitive decline and AD. However, the precise underlying mechanisms by which CIH contributes to cognitive impairment remain unknown. In the present study, we examined the effects of CIH on cognition and hippocampal function in APP/PS1 mice, an animal model of AD.

Methods: Wild-type (WT) and APP/PS1 mice were subjected to one of the following conditions for 2 weeks: (1) sham condition (continuous room air) or (2) CIH condition. The oxygen concentration of the CIH condition transitioned from 5 to 21%. Behavioral tests, electrophysiological recording, real-time polymerase chain reaction, and Western blot were used to assess the effect of CIH on cognitive performance and synaptic plasticity.

Results: CIH exposure did not affect motor coordination, general locomotor activity, anxiety, or willingness to explore. However, behavioral test results indicated that APP/PS1-CIH mice showed more spatial learning and memory deficits. CIH induced long-term potentiation (LTP) dysfunction of the hippocampus in WT mice. These effects were aggravated in APP/PS1 mice. The N-methyl-D-aspartic acid receptor (NMDAR) NR1 subunit and postsynaptic density 95 (PSD95) in the hippocampus of WT and APP/PS1 mice were downregulated.

Conclusions: These findings showed that a postsynaptic mechanism was involved in the effect of CIH on cognitive impairment.

Citing Articles

Intermittent Hypoxia as a Model of Obstructive Sleep Apnea: Present and Future.

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PMID: 39894602 PMC: 11788578. DOI: 10.1016/j.jsmc.2024.10.009.

The relationship between hypoxia and Alzheimer's disease: an updated review.

Tao B, Gong W, Xu C, Ma Z, Mei J, Chen M Front Aging Neurosci. 2024; 16:1402774.

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