Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep, 2025, Natalie L Hauglund et al

[Mij]

Highlights
•
Norepinephrine release from the locus coeruleus drives slow vasomotion in NREM sleep
•
Infraslow norepinephrine oscillations control opposing changes in blood and CSF volumes
•
Norepinephrine oscillation frequency during NREM sleep predicts glymphatic clearance
•
The sleep aid zolpidem suppresses norepinephrine oscillations and glymphatic flow

Summary
As the brain transitions from wakefulness to sleep, processing of external information diminishes while restorative processes, such as glymphatic removal of waste products, are activated. Yet, it is not known what drives brain clearance during sleep.

We here employed an array of technologies and identified tightly synchronized oscillations in norepinephrine, cerebral blood volume, and cerebrospinal fluid (CSF) as the strongest predictors of glymphatic clearance during NREM sleep. Optogenetic stimulation of the locus coeruleus induced anti-correlated changes in vasomotion and CSF signal. Furthermore, stimulation of arterial oscillations enhanced CSF inflow, demonstrating that vasomotion acts as a pump driving CSF into the brain.

On the contrary, the sleep aid zolpidem suppressed norepinephrine oscillations and glymphatic flow, highlighting the critical role of norepinephrine-driven vascular dynamics in brain clearance. Thus, the micro-architectural organization of NREM sleep, driven by norepinephrine fluctuations and vascular dynamics, is a key determinant for glymphatic clearance.
LINK

 

[Ravn]

in mice

Danish article about this study with brief mention of CFS (which doesn't appear to figure in the study itself, assuming my word search didn't miss it)

But just as importantly, the new knowledge about noradrenaline also provides a potentially new understanding of chronic fatigue syndrome, where you feel tired even though you are asleep [auto-translate may have been the one asleep here].
The condition cannot be diagnosed by standard sleep studies because nothing abnormal shows up on the EEG, which measures the brain's electrical activity.
“This may indicate that the pumps are not working in chronic fatigue syndrome and that sleep does not cleanse the brain sufficiently,” says Maiken Nedergaard.

 

[SNT Gatchaman]

Also an article in Science —

https://www.science.org/content/article/scientists-uncover-how-brain-washes-itself-during-sleep

 

[Murph]

POssible linkages here from adrenergic theories of me/cfs / cerebral blood flow theories of mecfs to why sleep is non-restorative in me/cfs, but you'd need a lot more work to establish them as any sort of fact.
Still, could be worth someone applying for funding to look at cerebral blood flow during sleep and adrenergic markers in pwme and controls.

 

[EndME]

POssible linkages here from adrenergic theories of me/cfs / cerebral blood flow theories of mecfs to why sleep is non-restorative in me/cfs, but you'd need a lot more work to establish them as any sort of fact.
Still, could be worth someone applying for funding to look at cerebral blood flow during sleep and adrenergic markers in pwme and controls.

Or perhaps the different levels of Norepinephrine between ME/CFS and HC's recorded in the intramural study?

 

[hotblack]

And a write up on Arstechnica
https://arstechnica.com/science/202...-with-the-brains-internal-cleaning-mechanism/

I was also pondering potential ME/CFS relationships too. Either something disrupting norepinephrine and this process which triggers some symptoms or perhaps something else causing a build up of junk and the brain/body responds with increases in norepinephrine to try to clean up with this process.

Given this how this process is theorised to work I’m not sure if just checking norepinephrine levels in blood would tell us much? And I don’t think anyone would want the same sort of investigations that the mice had…

 

[Sean]

POssible linkages here from adrenergic theories of me/cfs / cerebral blood flow theories of mecfs to why sleep is non-restorative in me/cfs, but you'd need a lot more work to establish them as any sort of fact.
Still, could be worth someone applying for funding to look at cerebral blood flow during sleep and adrenergic markers in pwme and controls.

Definitely worth looking into.