Sleep deprivation impairs molecular clearance from the human brain.
Sleep deprivation impairs molecular clearance from the human brain.
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DOI：
10.1093/brain/awaa443
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发表时间：
2021-04-12
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影响因子：
--
通讯作者：
Ringstad, Geir
中科院分区：
文献类型：
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作者：
Eide, Per Kristian;Vinje, Vegard;Ringstad, Geir
为什么人的一生中有三分之一的时间是在睡觉，这仍然是一个谜。实验数据表明，睡眠是清除大脑代谢废物所必需的。然而，这一点从未在人类身上得到证实。本研究的主要目的是在体内研究一个晚上的完全睡眠剥夺是否会影响人类大脑的分子清除。其次，我们研究了清除率是否受到随后睡眠的影响。在鞘内注射造影剂钆布醇（0.5 ml，1 mmol/ml）（作为示踪分子）后48 h内进行标准化T1序列的多相MRI。使用FreeSurfer软件，我们量化了85个脑区域内的示踪剂富集，作为标准化T1信号从基线的百分比变化。在两个个体队列之间比较大脑示踪剂富集;一个队列（n=7）从第1天到第2天（睡眠剥夺组）进行完全睡眠剥夺，而年龄和性别匹配的对照组（n=17;睡眠组）从第1天到第2天允许自由睡眠。从第2天到第3天，所有个体都允许自由睡眠。示踪剂同样丰富了两组人的大脑。睡眠剥夺是唯一的干预措施。如干预（睡眠剥夺/睡眠）后第2天早晨所示，一夜睡眠剥夺损害了示踪物质从大部分脑区域（包括大脑皮层、白色物质和边缘结构）的清除。此外，睡眠剥夺组中受损的脑清除率在第2天至第3天的后续睡眠中没有得到补偿。目前的结果提供了体内证据，证明一夜的完全睡眠剥夺会损害人类大脑的分子清除，并且人类不会弥补失去的睡眠。
It remains an enigma why human beings spend one-third of their life asleep. Experimental data suggest that sleep is required for clearance of waste products from brain metabolism. This has, however, never been verified in humans. The primary aim of the present study was to examine in vivo whether one night of total sleep deprivation affects molecular clearance from the human brain. Secondarily, we examined whether clearance was affected by subsequent sleep. Multiphase MRI with standardized T1 sequences was performed up to 48 h after intrathecal administration of the contrast agent gadobutrol (0.5 ml of 1 mmol/ml), which served as a tracer molecule. Using FreeSurfer software, we quantified tracer enrichment within 85 brain regions as percentage change from baseline of normalized T1 signals. The cerebral tracer enrichment was compared between two cohorts of individuals; one cohort (n=7) underwent total sleep deprivation from Day 1 to Day 2 (sleep deprivation group) while an age and gender-matched control group (n=17; sleep group) was allowed free sleep from Day 1 to Day 2. From Day 2 to 3 all individuals were allowed free sleep. The tracer enriched the brains of the two groups similarly. Sleep deprivation was the sole intervention. One night of sleep deprivation impaired clearance of the tracer substance from most brain regions, including the cerebral cortex, white matter and limbic structures, as demonstrated on the morning of Day 2 after intervention (sleep deprivation/sleep). Moreover, the impaired cerebral clearance in the sleep deprivation group was not compensated by subsequent sleep from Day 2 to 3. The present results provide in vivo evidence that one night of total sleep deprivation impairs molecular clearance from the human brain, and that humans do not catch up on lost sleep.