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睡眠行为改变增强了阿尔茨海默病 ArcAβ 小鼠模型的表面效度。

Altered sleep behavior strengthens face validity in the ArcAβ mouse model for Alzheimer's disease.

机构信息

Department of Anesthesiology and Intensive Care, School of Medicine and Health, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

出版信息

Sci Rep. 2024 Jan 10;14(1):951. doi: 10.1038/s41598-024-51560-3.

DOI:10.1038/s41598-024-51560-3
PMID:38200079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10781983/
Abstract

Demographic changes will expand the number of senior citizens suffering from Alzheimer's disease (AD). Key aspects of AD pathology are sleep impairments, associated with onset and progression of AD. AD mouse models may provide insights into mechanisms of AD-related sleep impairments. Such models may also help to establish new biomarkers predicting AD onset and monitoring AD progression. The present study aimed to establish sleep-related face validity of a widely used mouse model of AD (ArcAβ model) by comprehensively characterizing its baseline sleep/wake behavior. Chronic EEG recordings were performed continuously on four consecutive days in freely behaving mice. Spectral and temporal sleep/wake parameters were assessed and analyzed. EEG recordings showed decreased non-rapid eye movement sleep (NREMS) and increased wakefulness in transgenic mice (TG). Vigilance state transitions were different in TG mice when compared to wildtype littermates (WT). During NREMS, TG mice had lower power between 1 and 5 Hz and increased power between 5 and 30 Hz. Sleep spindle amplitudes in TG mice were lower. Our study strongly provides sleep-linked face validity for the ArcAβ model. These findings extend the potential of the mouse model to investigate mechanisms of AD-related sleep impairments and the impact of sleep impairments on the development of AD.

摘要

人口结构变化将使老年痴呆症(AD)患者数量增加。AD 病理学的关键方面是睡眠障碍,与 AD 的发病和进展有关。AD 小鼠模型可以深入了解 AD 相关睡眠障碍的机制。这些模型还可以帮助建立新的生物标志物,用于预测 AD 的发病和监测 AD 的进展。本研究旨在通过全面描述其基线睡眠/觉醒行为,为广泛使用的 AD 小鼠模型(ArcAβ 模型)建立与睡眠相关的表面效度。在自由活动的小鼠上连续进行了四天的慢性 EEG 记录。评估和分析了光谱和时间睡眠/觉醒参数。脑电图记录显示,转基因小鼠(TG)的非快速眼动睡眠(NREMS)减少,觉醒增加。与野生型同窝仔鼠(WT)相比,TG 小鼠的警觉状态转换不同。在 NREMS 期间,TG 小鼠的 1 至 5 Hz 之间的功率较低,而 5 至 30 Hz 之间的功率增加。TG 小鼠的睡眠纺锤波振幅较低。我们的研究为 ArcAβ 模型提供了强有力的与睡眠相关的表面效度。这些发现扩展了小鼠模型在研究 AD 相关睡眠障碍机制以及睡眠障碍对 AD 发展影响方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa9/10781983/5b8405eb9b9c/41598_2024_51560_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa9/10781983/1f2077d43b53/41598_2024_51560_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa9/10781983/5051c0ec0046/41598_2024_51560_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa9/10781983/ee2fa0336848/41598_2024_51560_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa9/10781983/a3191996fe48/41598_2024_51560_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa9/10781983/5b8405eb9b9c/41598_2024_51560_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa9/10781983/1f2077d43b53/41598_2024_51560_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa9/10781983/5051c0ec0046/41598_2024_51560_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa9/10781983/ee2fa0336848/41598_2024_51560_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa9/10781983/a3191996fe48/41598_2024_51560_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa9/10781983/5b8405eb9b9c/41598_2024_51560_Fig5_HTML.jpg

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