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慢性睡眠剥夺对家族性阿尔茨海默病(5xFAD)小鼠模型中与年龄相关的神经退行性变的影响

Contribution of Chronic Sleep Deprivation to Age-Related Neurodegeneration in a Mouse Model of Familial Alzheimer's Disease (5xFAD).

作者信息

Klimenko Maria O, Mishchenko Tatiana A, Mitaeva Yaroslava I, Kondakova Elena V, Mitroshina Elena V, Vedunova Maria V

机构信息

Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia.

出版信息

Neurol Int. 2023 Jun 27;15(3):778-791. doi: 10.3390/neurolint15030049.

DOI:10.3390/neurolint15030049
PMID:37489355
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10366916/
Abstract

Sleep-wake cycle disorders most often accompany the elderly and are frequently associated with the development of neurodegenerative processes, primarily Alzheimer's disease. Sleep disturbances can be diagnosed in patients with AD even before the onset of memory and cognitive impairment, and become more pronounced as the disease progresses. Therefore, the expansion of our knowledge of how sleep relates to AD pathogenesis needs to be addressed as soon as possible. Here, we investigated the influence of chronic sleep deprivation on the motor and orienting-exploratory activity of 5xFAD mice, as well as their spatial learning ability and long-term memory retention. The studies carried out revealed that chronic sleep deprivation negatively affects the processes of spatial memory reconsolidation in 5xFAD mice. This leads to the development of stress-related behavioral responses, including aggressive behavior. In addition, the morphological changes in the cerebral cortex, including changes in the nuclear-cytoplasmic ratio and degradation of neuronal processes are observed. Moreover, we found an increase in the level of total DNA methylation in the blood of the sleep-deprived mice, which may be one of the mechanisms of the two-way relationship between sleep and neurodegeneration.

摘要

睡眠-觉醒周期障碍最常出现在老年人身上,并且经常与神经退行性过程的发展相关,主要是阿尔茨海默病。在患有阿尔茨海默病的患者中,甚至在记忆和认知障碍出现之前就可以诊断出睡眠障碍,并且随着疾病的进展而变得更加明显。因此,需要尽快解决我们对睡眠与阿尔茨海默病发病机制之间关系的认识扩展问题。在这里,我们研究了慢性睡眠剥夺对5xFAD小鼠运动和定向探索活动的影响,以及它们的空间学习能力和长期记忆保持能力。进行的研究表明,慢性睡眠剥夺对5xFAD小鼠的空间记忆再巩固过程有负面影响。这导致与应激相关的行为反应的发展,包括攻击性行为。此外,观察到大脑皮层的形态变化,包括核质比的变化和神经元突起的退化。此外,我们发现睡眠剥夺小鼠血液中总DNA甲基化水平升高,这可能是睡眠与神经退行性变双向关系的机制之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/63324df6757d/neurolint-15-00049-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/782c41742eaf/neurolint-15-00049-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/c4c3161b01ad/neurolint-15-00049-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/10f6290206d9/neurolint-15-00049-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/45c6c355183c/neurolint-15-00049-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/6fd84769e85b/neurolint-15-00049-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/63324df6757d/neurolint-15-00049-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/782c41742eaf/neurolint-15-00049-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/c4c3161b01ad/neurolint-15-00049-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/10f6290206d9/neurolint-15-00049-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/45c6c355183c/neurolint-15-00049-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/6fd84769e85b/neurolint-15-00049-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/10366916/63324df6757d/neurolint-15-00049-g006.jpg

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