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阿尔茨海默病各种转基因小鼠模型中的进行性睡眠障碍。

Progressive sleep disturbance in various transgenic mouse models of Alzheimer's disease.

作者信息

Drew Victor J, Wang Chanung, Kim Tae

机构信息

Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.

Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States.

出版信息

Front Aging Neurosci. 2023 May 19;15:1119810. doi: 10.3389/fnagi.2023.1119810. eCollection 2023.

Abstract

Alzheimer's disease (AD) is the leading cause of dementia. The relationship between AD and sleep dysfunction has received increased attention over the past decade. The use of genetically engineered mouse models with enhanced production of amyloid beta (Aβ) or hyperphosphorylated tau has played a critical role in the understanding of the pathophysiology of AD. However, their revelations regarding the progression of sleep impairment in AD have been highly dependent on the mouse model used and the specific techniques employed to examine sleep. Here, we discuss the sleep disturbances and general pathology of 15 mouse models of AD. Sleep disturbances covered in this review include changes to NREM and REM sleep duration, bout lengths, bout counts and power spectra. Our aim is to describe in detail the severity and chronology of sleep disturbances within individual mouse models of AD, as well as reveal broader trends of sleep deterioration that are shared among most models. This review also explores a variety of potential mechanisms relating Aβ accumulation and tau neurofibrillary tangles to the progressive deterioration of sleep observed in AD. Lastly, this review offers perspective on how study design might impact our current understanding of sleep disturbances in AD and provides strategies for future research.

摘要

阿尔茨海默病(AD)是痴呆症的主要病因。在过去十年中,AD与睡眠功能障碍之间的关系受到了越来越多的关注。使用淀粉样β蛋白(Aβ)生成增加或tau蛋白过度磷酸化的基因工程小鼠模型,在理解AD的病理生理学方面发挥了关键作用。然而,它们关于AD中睡眠障碍进展的揭示高度依赖于所使用的小鼠模型以及用于检查睡眠的特定技术。在此,我们讨论15种AD小鼠模型的睡眠障碍和一般病理学。本综述涵盖的睡眠障碍包括非快速眼动(NREM)和快速眼动(REM)睡眠持续时间、发作时长、发作次数和功率谱的变化。我们的目的是详细描述AD个体小鼠模型中睡眠障碍的严重程度和时间顺序,并揭示大多数模型共有的睡眠恶化的更广泛趋势。本综述还探讨了与Aβ积累和tau神经原纤维缠结相关的各种潜在机制,这些机制与AD中观察到的睡眠逐渐恶化有关。最后,本综述就研究设计如何影响我们目前对AD中睡眠障碍问题的理解提供了观点,并为未来研究提供了策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d2a/10235623/cc516985f610/fnagi-15-1119810-g001.jpg

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