Pathophysiology of sleep disturbances/unrefreshing sleep in pwME?

[rapidboson]

Sleep seems to be important for forming memories but an important part of that may be forgetting. Sleep may serve the function of erasing useless information from short term store while securing useful memories. In the past I have wondered whether the problem in ME/CFS may be a failure to 'forget' material from yesterday. Hence the interest in complement regulatory proteins since complement is apparently necessary for this forgetting process.

Interesting angle! As an analogy, would you in that case contribute e.g. impaired working memory with running out of RAM to process/save new information? Though the brain surely is more complex than this analogy would make it sound.

Do you know in which sleep stage this complement-mediated forgetting happens?

 

[Jonathan Edwards]

As an analogy, would you in that case compare e.g. impaired working memory with running out of RAM to process/save new information?

Yes.

Do you know in which sleep stage this complement-mediated forgetting happens?

No idea.

 

[rapidboson]

There was just a presentation of the "Sleep-Neuro-Path" study in Germany. More info here. Will share some screenshots of disturbances they found in (if I understood correctly) studies done before this new study. Seem to have found a difference in sleep spindles in NREM2 and will now look deeper into it and additionally check brainstem signals (arousals).
Very interesting stuff.

 

[rapidboson]

Here are the screenshots - I hope it's OK to share them here. Papers in preparation it says.

So they seem to have seen decreased sleep spindles in long COVID patients. Some potential correlations to ACE2-AAbs and serum MDA.
Will be interesting to see the bigger cohort where they will in addition to the thalamo-cortical network also monitor brainstem (HRV, arousals etc).

 

[Nightsong]

Sleep seems to be important for forming memories but an important part of that may be forgetting. Sleep may serve the function of erasing useless information from short term store while securing useful memories. In the past I have wondered whether the problem in ME/CFS may be a failure to 'forget' material from yesterday. Hence the interest in complement regulatory proteins since complement is apparently necessary for this forgetting process.

Is there any broader evidence for the role of complement in sleep-dependent memory pruning in humans? - in mice there is e.g. the Wang et al demonstration of the engulfment of synaptic components by microglia & that boosting CD55 prevented C1q/C3 tagging & protected memories from microglial pruning.

There's some evidence that certain signalling molecules (complement, ephrin) are affected by sleep deprivation (e.g. in Lucey et al (found C1q/C4-pathway proteins upregulated in CSF after one night without sleep) & Reis et al (showed blunted nocturnal C3a after 24 h wakefulness), & some additional evidence from studies of mild TBI. It's an interesting idea - also reminds me a little of the famous REM-dreaming Crick-Mitchison hypothesis (or, if you go well back into medical history, to William James).

 

[Jonathan Edwards]

Is there any broader evidence for the role of complement in sleep-dependent memory pruning in humans?

I don't think so. I think the data are from mice, as you say.

 

[Jonathan Edwards]

Zhang et al. pulled out three genes related to adenosine metabolism and apparently adenosine is important in sleep pattern. Alleles cover risk for insomnia for instance.