Posted by A study published in Proceedings of the National Academy of Sciences (https://www.pnas.org/doi/10.1073/pnas.2523438123) suggests that lack of sleep harms the fatty insulation that protects nerve cells in the brain. Fatigue and slower reflexes the next day are commonly blamed on overworked neurons, the underlying biology has remained unclear. It was suspected that additional mechanisms might be involved and these were set out to be explored.
Looking for the source
Researchers led by scientists at the University of Camerino in Italy first analyzed MRI scans from 185 volunteers who reported poor sleep quality. The scans supported earlier findings linking insufficient sleep to structural changes in white matter—the nerve fiber pathways that transmit signals throughout the brain. To pinpoint the cause, the scientists then conducted experiments on rats whose sleep was restricted for ten days.
Electrical measurements revealed that sleep deprivation slowed nerve signal transmission between the brain’s hemispheres by about 33%. Examination of brain tissue provided a likely explanation: the myelin sheaths surrounding nerve fibers were significantly thinner. Myelin is a fatty coating that insulates neurons and enables rapid electrical communication.
A cholesterol traffic jam
Further analysis of brain lipids and gene activity in oligodendrocytes—the cells responsible for producing and maintaining myelin—pointed to a shortage of cholesterol. Although cholesterol is essential for healthy myelin, it was not being efficiently delivered to the sheaths. As a result, the insulation deteriorated and signal transmission slowed.
To test this idea, the researchers treated the sleep-deprived rats with subcutaneous (2 g / bwkg) 2-hydroxypropyl beta cyclodextrin (HPBCD), which is thought to release trapped cholesterol back into circulation. Three injections of cyclodextrin were delivered over 10 days of sleep restriction. The treatment prevented further thinning of myelin, restored normal signal speed, and eliminated the 33% delay. In behavioral tests, the treated rats performed as well (in novel object discrimination) as animals that had not been sleep deprived.
While the findings are too preliminary to suggest treatments for sleep loss in humans, they open intriguing new avenues for research. If similar mechanisms are confirmed in people, they could point toward novel therapeutic strategies.
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