Sleep deprivation impairs molecular clearance from the human brain, Eide et al, 2021

cassava7

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Per Kristian Eide, Vegard Vinje, Are Hugo Pripp, Kent-Andre Mardal, Geir Ringstad

Brain, Volume 144, Issue 3, March 2021, Pages 863–874, https://doi.org/10.1093/brain/awaa443

Published: 23 March 2021

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.



Commentary: "A step forward in understanding the role of sleep and its link to neurodegeneration", Stefani and Högl
 
There was another research paper last year that explained how the slow brainwaves of deep sleep helped pump fluids from the brain. Astrocytes also open the BBB a bit during sleep to transfer waste out. I'm not sure whether they used markers to prove it.

I've just posted the paper that you might be thinking of: here.
 
The commentary paper said:
Over the past few years, sleep disorders have increasingly been recognized as being among the earliest signs of ongoing neurodegeneration, suggesting that they may be risk factors for the development of neurodegenerative disease. However, despite growing data on this topic, how sleep is linked to neurodegeneration remains a largely open question with many issues yet to be addressed. In this issue of Brain, Eide and co-workers provide an important piece of this complex puzzle.

Back in 2012, a completely new path in the field of sleep and neurodegeneration was paved with the first description of the glymphatic—or ‘glial-dependent lymphatic’—system (Fig. 1). This system was initially identified in mice as a brain-wide pathway for fluid transport, dependent upon trans-astrocytic water movement. The article that provided the first description of the glymphatic system also reported its critical role in the clearance of brain interstitial solutes including soluble amyloid-β1–40. Subsequent work has shown that this glial cell-dependent paravascular network not only removes soluble proteins and metabolites from the CNS, but also supplies the brain with glucose, lipids and neuromodulators. However, the existence of this glymphatic system still does not sufficiently explain how sleep disruption may lead to or contribute to the onset of neurodegeneration.

Further insights came from the finding that there is a 90% reduction in glymphatic clearance during wakefulness, and that the clearance of amyloid-β from the brain doubles during sleep whereas sleep deprivation leads to a reduction in CSF metabolite removal. These findings offer a possible explanation for the biological need for sleep and for why loss of sleep is linked to neurodegeneration. If sleep disruption leads to impaired functioning of the glymphatic system, then the subsequent reduction in clearance of waste products may lead to the accumulation of pathological proteins in the brain, and eventually trigger neurodegeneration.

In the video, it isn't made clear that when it is said that further sleep does not clear their tracer, they mean only that it wasn't cleared after 48 hours, when they did a second scan; the first scan being after one night of sleep deprivation and sleep being allowed the second night (with the contol group sleeping normally throughout). After four weeks, all the tracer was cleared in both groups. The moral of the story seems to be that more than one night of catch-up sleep is required after an episode of poor sleep, which fits with my experience. But others might have more serious dysfunctions, of course.
 
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