Chen Lihong, Huang Junshan, Yang Lanfang, Zeng Xue-Ai, Zhang Ya, Wang Xiufeng, Chen Mingqi, Li Xing, Zhang Yifan, Zhang Min
Fujian Institute of Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fujian, 350003, China.
Fujian Institute of Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fujian, 350003, China.
Neurosci Lett. 2017 May 22;650:146-152. doi: 10.1016/j.neulet.2017.04.047. Epub 2017 Apr 25.
Sleep disorders have previously been connected with the neurodegenerative pathology of Alzheimer's disease (AD) due to the aggregation of β-amyloid(Aβ)peptides and tau proteinsinduced by sleep deprivation (SD). However, the underlying mechanisms remain unclear. Therefore, this study was performed to clarify how Aβ-related metabolism is regulated after SD. Three-month-old Sprague-Dawley rats (250-300g) were randomly divided into 5 groups: two SD groups(i.e.,SD-2d and SD-4d), two platform control groups(i.e.,PC-2d and PC-4d) and a home cage control group (CC). For the two SD groups, themodified multiple platform method (MMPM) was used to induce SD.Our experiments confirmed that SD impaired cognitive function and increased the levels of Aβ peptides, a hallmark of AD. Additionally, we found that SD significantly increasedthe levels of the β-site amyloid precursor protein (APP)-cleaving enzyme 1(BACE1, β-secretase), but had little impacton the levels of Aβ-degradationenzymes.This resultmay be the main cause of the over-expression of Aβ1-42 and Aβ1-40. Our results suggested that SD accelerates the progression of AD bymodulating Aβ-related metabolism. This findinghasimportant implications for the diagnosis and prevention of AD.
睡眠障碍先前已因睡眠剥夺（SD）诱导的β-淀粉样蛋白（Aβ）肽和tau蛋白聚集而与阿尔茨海默病（AD）的神经退行性病理相关联。然而，其潜在机制仍不清楚。因此，本研究旨在阐明睡眠剥夺后Aβ相关代谢是如何被调节的。将3个月大的Sprague-Dawley大鼠（250 - 300克）随机分为5组：两个睡眠剥夺组（即SD - 2d和SD - 4d）、两个平台对照组（即PC - 2d和PC - 4d）和一个饲养笼对照组（CC）。对于两个睡眠剥夺组，采用改良多平台法（MMPM）诱导睡眠剥夺。我们的实验证实，睡眠剥夺损害了认知功能并增加了Aβ肽水平，这是AD的一个标志。此外，我们发现睡眠剥夺显著增加了β-位点淀粉样前体蛋白（APP）裂解酶1（BACE1，β-分泌酶）的水平，但对Aβ降解酶的水平影响不大。这一结果可能是Aβ1 - 42和Aβ1 - 40过度表达的主要原因。我们的结果表明，睡眠剥夺通过调节Aβ相关代谢加速了AD的进展。这一发现对AD的诊断和预防具有重要意义。
