Sleep loss damages the fatty insulation protecting the nerve cells in our brain, according to a paper published in the journal Proceedings of the National Academy of Sciences. The research also explains why we often feel slow and groggy after a bad night’s sleep.
Most of us will experience sleep loss at one time or another and suffer the consequences of tiredness and slower reactions the next day. The biological mechanisms for these are not well understood and often attributed to tired or overworked neurons. Researchers led by scientists at the University of Camerino in Italy thought there might be other factors at play, so they decided to investigate.
Searching for the cause
The team studied MRI scans of 185 volunteers who self-reported poor sleep quality, which confirmed previous studies that found a link between inadequate sleep and changes in the structure of white matter (the bundles of nerve fibers that carry impulses between neurons). To find the cause, the researchers ran tests on rats that had their sleep restricted for ten days.
First, they performed electrical tests on the rats’ brains and discovered that sleep loss caused nerve signals to take around 33% longer to travel between the two hemispheres. Later analysis of brain tissue found a likely cause. The myelin sheaths were much thinner. These are the fatty layers that wrap around nerve fibers to insulate them and speed up electrical signals.
Cholesterol bottleneck
Analysis of the lipid composition of the brain and the activity of genes that regulate oligodendrocytes revealed that the main issue was cholesterol deficiency. The scientists focused on these cells because they are responsible for creating and maintaining myelin. They found that cholesterol, which is essential for keeping the insulation thick and healthy, was not being properly transported to the myelin sheaths, so they were thinner and less able to do their job.
To test this, the researchers administered a compound called cyclodextrin, which works to flush trapped cholesterol out of cells and back into circulation. This prevented myelin sheaths from thinning any further and eliminated the roughly 33% delay in signal speed. In behavioral tests, the rodents performed just as well as those that were well-rested.
It is too early to talk about treatments for sleep deprivation based on the conclusions of this study. However, if confirmed in humans, the results would open up new possibilities, as the researchers acknowledge in their paper.
“Our findings highlight a possible role of oligodendrocyte cholesterol dysregulation in behavioral deficits associated with sleep loss and unveil a novel target for intervention,” said the researchers.
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Publication details
Reyila Simayi et al, Sleep loss induces cholesterol-associated myelin dysfunction, Proceedings of the National Academy of Sciences (2026). DOI: 10.1073/pnas.2523438123
Journal information:
Proceedings of the National Academy of Sciences
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