List of causation hypothesis for follow up after DecodeME

[SNT Gatchaman]

Re: MAIT T cells being found in the meninges in Mucosal-associated invariant T cells restrict reactive oxidative damage and preserve meningeal barrier integrity and cognitive function (2022)

It has nothing to do with trafficking

Yes the claim is that they're tissue-resident, as part of the barrier function of meninges. From the editorial on the Zhang paper Meningeal MAIT cells maintain meningeal and brain function (2022) —

the meninges, a trilayer structure composed of the parenchyma-adjacent pia, the highly vascular arachnoid, and the outermost dense dura mater, contain various resident lymphocyte subsets, including innate lymphoid cells and γδ T cells in the non-inflamed state. The presence of these immune cells may affect cognition and memory, although the mechanisms underlying their function in this context are incompletely understood. Zhang et al. now add MAIT cells to the lymphocyte meningeal repertoire, exploring their importance for the integrity of protective barriers and how their loss affects homeostatic mechanisms that limit neuroinflammation.

 

[chillier]

I’m not a neuroscience person so maybe I’m missing some important context—but if it had to do with something traveling down a neuron that wasn’t an action potential, wouldn’t you expect the progression of PEM to be more, well, progressive across the body based on shortest to longest axonal length? I definitely get whole-body muscle weakness, stiffness, and pain as part of PEM and sometimes symptoms have a temporal offset between them, but not in any way that would correspond to neuron length. For me, it’s more that pain/stiffness/weakness is the worst in the muscle groups that I was using during activity, and then everywhere else it builds at the same rate and around the same intensity.

For that particular idea, it wouldn't be that you would feel PEM in different places over time. It would be that signals from eg just used muscles would take a while to reach the neuron nuclei and cause a transcriptional response, but once it did the whole neuron could be eg sensitised at once leading then to PEM (which is a whole body feeling, at least for me). In other words the length of the axons would correspond to how soon PEM is felt, not where it is felt.

Anyway I think the scaling idea might be a bit better.

 

[jnmaciuch]

I just wonder whether it would be worth looking for links with migraine on the basis that that seems to be another situation where a brain loop generates signals that should not be there.

Could you share any relevant papers about this? I read up on migraine quite often since several people in my life suffer from them, and have not come across any papers showing that migraine occurs when the brain generates a signal that should not be there. Spreading depolarization is the opposite phenomenon and next to nothing is known about what causes SD.

 

[DMissa]

@DMissa not sure if this is the right place to post this, but if you’re doing any high throughput screeen automation I’m happy to donate my time. I’m an automation engineer with 7+ years of experience in biotech specializing in high throughput screening on liquid handlers: Hamilton, Beckman (Bravos & echo), Tecans, thermo-fisher work cells, and custom integration work cells.

I’ve ask OMF in the past but have learned it’s cheaper outside of biotech to just hire grad students to pipette instead of buying robotics. If anyone working on CFS needs automation consulting happy to donate my time.

Thank you, and noted, but yes as you might imagine the obstacle is capital

 

[Hutan]

Please discuss the utility of AI/large language models for generating hypotheses here:
Can Large Language Models (LLMs) like ChatGPT be used to produce useful information?

We've moved some posts on that topic to that thread.

 

[Kitty]

For that particular idea, it wouldn't be that you would feel PEM in different places over time. It would be that signals from eg just used muscles would take a while to reach the neuron nuclei and cause a transcriptional response, but once it did the whole neuron could be eg sensitised at once leading then to PEM (which is a whole body feeling, at least for me).

Could molecules such as prostaglandins interact with this idea?

I keep thinking about the 'immune' symptoms in PEM, and prostaglandins could potentially be behind head-cold and gut symptoms. (They may also be implicated in 'period 'flu', the symptoms of which are the same as day 1 PEM.)

One of the things that prompts release from cells is injury, and I've wondered if alert signals could somehow be triggered when there is no injury, just activity.

Ignore me if I'm talking rubbish again, I really don't know anything!