Loss of Sleep Affects the Ultrastructure of Pyramidal Neurons in the Adolescent Mouse Frontal Cortex
Loss of Sleep Affects the Ultrastructure of Pyramidal Neurons in the Adolescent Mouse Frontal Cortex
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DOI：
10.5665/sleep.5644
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发表时间：
2016-04-01
期刊：
影响因子：
5.6
通讯作者：
Cirelli, Chiara
中科院分区：
文献类型：
--
作者：
de Vivo, Luisa;Nelson, Aaron B.;Cirelli, Chiara
研究目的：青少年大脑可能受到急性睡眠剥夺（ASD）和慢性睡眠限制（CSR）的独特影响，但缺乏直接证据。我们使用电子显微镜研究了ASD和CSR如何影响青春期小鼠额叶皮层的锥体神经元，重点关注线粒体、核内体和溶酶体，它们共同执行最基本的细胞功能，从营养摄入到预防细胞应激。方法：青春期（1个月大）小鼠在光期的前6-8小时睡眠(S)或睡眠剥夺（ASD，有新物体和跑步轮），慢性睡眠限制（CSR） bbbb4天（使用新物体，跑步轮，社交互动，强迫运动，含咖啡因的水），或允许恢复睡眠（RS）类似于CSR后32小时。对350个锥体神经元进行超微结构分析（S = 82; ASD = 86; CSR = 103; RS = 79； 4 ~ 5只/组）。结果：S与ASD、S与CSR、CSR与RS以及S与RS之间的一些超微结构参数存在差异，尽管用于强制唤醒的不同方法可能导致了短睡眠和长睡眠缺失之间的一些差异。差异包括CSR与S相比，线粒体占据的细胞质面积更大，CSR与S和RS相比，次级溶酶体数量更多。我们还发现，睡眠不足可能会揭示在基线睡眠期间不明显的个体间差异。此外，使用11个超微结构参数的组合，我们可以在高达80%的病例中预测睡眠或觉醒是否发生在单细胞水平。结论：超微结构分析可能是一种强有力的工具，可以识别哪些细胞器，从而确定哪些细胞功能最受睡眠和睡眠不足的影响。
Study Objective: The adolescent brain may be uniquely affected by acute sleep deprivation (ASD) and chronic sleep restriction (CSR), but direct evidence is lacking. We used electron microscopy to examine how ASD and CSR affect pyramidal neurons in the frontal cortex of adolescent mice, focusing on mitochondria, endosomes, and lysosomes that together perform most basic cellular functions, from nutrient intake to prevention of cellular stress.Methods: Adolescent (1-mo-old) mice slept (S) or were sleep deprived (ASD, with novel objects and running wheels) during the first 6-8 h of the light period, chronically sleep restricted (CSR) for > 4 days (using novel objects, running wheels, social interaction, forced locomotion, caffeinated water), or allowed to recover sleep (RS) for similar to 32 h after CSR. Ultrastructural analysis of 350 pyramidal neurons was performed (S = 82; ASD = 86; CSR = 103; RS = 79; 4 to 5 mice/group).Results: Several ultrastructural parameters differed in S versus ASD, S versus CSR, CSR versus RS, and S versus RS, although the different methods used to enforce wake may have contributed to some of the differences between short and long sleep loss. Differences included larger cytoplasmic area occupied by mitochondria in CSR versus S, and higher number of secondary lysosomes in CSR versus S and RS. We also found that sleep loss may unmask interindividual differences not obvious during baseline sleep. Moreover, using a combination of 11 ultrastructural parameters, we could predict in up to 80% of cases whether sleep or wake occurred at the single cell level.Conclusions: Ultrastructural analysis may be a powerful tool to identify which cellular organelles, and thus which cellular functions, are most affected by sleep and sleep loss.