Late-in-life neurodegeneration after chronic sleep loss in young adult mice.
Late-in-life neurodegeneration after chronic sleep loss in young adult mice.
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DOI：
10.1093/sleep/zsab057
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发表时间：
2021-08-13
期刊：
影响因子：
5.6
通讯作者：
Veasey S
中科院分区：
文献类型：
--
作者：
Owen JE;Zhu Y;Fenik P;Zhan G;Bell P;Liu C;Veasey S
慢性短睡眠在现代社会中很普遍，已被认为是阿尔茨海默病(AD)的危险因素。此外，短期睡眠不足会显著增加野生型(WT)小鼠和人类的淀粉样蛋白β(Aβ)和tau的水平，睡眠障碍预示着老年人的认知能力下降。我们已经证明，在AD中，CS可导致蓝斑神经元(LCN)的损伤和丢失，蓝斑神经元具有高度易感性。然而，在没有阿尔茨海默病遗传风险的情况下，青年时期的CS是否会持续Aβ和/或tau变化和/或神经损伤还没有确定。在这里，我们研究了年轻成年WT小鼠暴露于css对两个AD脆弱神经元组-Lcn和海马CA1神经元-晚年Aβ和tau变化和神经反应的影响。染毒12个月后，染毒小鼠的CA1神经元数量和体积减少，空间记忆障碍，CA1神经胶质细胞激活，LCN丢失。Aβ 42和过度磷酸化的tau在CA1区增加，但没有观察到淀粉样斑块和tau缠结。总而言之，这些发现表明，在年轻成年小鼠中暴露于css会导致晚年神经退化，并导致淀粉样蛋白和tau蛋白稳态的持续紊乱。这些发现是在没有神经变性遗传易感性的情况下发生的，并首次证明了CS可以导致与晚发性AD的一些特征(但不是全部)一致的持久的、显著的神经损伤。
Chronic short sleep (CSS) is prevalent in modern societies and has been proposed as a risk factor for Alzheimer’s disease (AD). In support, short-term sleep loss acutely increases levels of amyloid β (Aβ) and tau in wild type (WT) mice and humans, and sleep disturbances predict cognitive decline in older adults. We have shown that CSS induces injury to and loss of locus coeruleus neurons (LCn), neurons with heightened susceptibility in AD. Yet whether CSS during young adulthood drives lasting Aβ and/or tau changes and/or neural injury later in life in the absence of genetic risk for AD has not been established. Here, we examined the impact of CSS exposure in young adult WT mice on late-in-life Aβ and tau changes and neural responses in two AD-vulnerable neuronal groups, LCn and hippocampal CA1 neurons. Twelve months following CSS exposure, CSS-exposed mice evidenced reductions in CA1 neuron counts and volume, spatial memory deficits, CA1 glial activation, and loss of LCn. Aβ 42 and hyperphosphorylated tau were increased in the CA1; however, amyloid plaques and tau tangles were not observed. Collectively the findings demonstrate that CSS exposure in the young adult mouse imparts late-in-life neurodegeneration and persistent derangements in amyloid and tau homeostasis. These findings occur in the absence of a genetic predisposition to neurodegeneration and demonstrate for the first time that CSS can induce lasting, significant neural injury consistent with some, but not all, features of late-onset AD.