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I noticed this paper being referenced by some organisations as evidence of biological changes after exertion and while it has been referenced on the forum we didn’t have a thread on it. So now we do!

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome Abstract Objectives. To determine mRNA expression differences in genes involved in signalling and modulating sensory fatigue, and muscle pain in patients...

Thanks. Unfortunately it doesn’t tell us much as far as I can tell, seems very much a drug company report on levels in the blood and safety rather than mechanisms. Why have they given it the silly acronym? Presumably to try and get a new patent or trade ark or whatever and make money of it as...

It’s described as a muscle relaxant, sort of, but seems related to tricyclic antidepressants. From wikipedia, also here’s a link to the info on what it acts on And has been doing the rounds for a while...

Interesting thanks. Yes that’s on the list. Looks to mainly affect D2 (and D2 like) and doesn’t seem to have shown up in any papers or theories posted to the forum. May be interesting looking at a wider search.

Ah, thanks, wasn’t sure if I’d missed something. I’m sure there’s all sorts of tangential or unknown effects of things :) It’s probably going to be complicated enough so am trying to stick to more clearly understood dopamine modifiers.

Looks to be an NSAID so more a COX inhibitor and unrelated to dopamine as far as I can tell?

This is less about ‘can we find a drug that works’ and more ‘can we learn anything about mechanisms’. I also think it may not be entirely black and white, neurotransmitters seem to have different effects in different cells. And the picture would likely get even more confusing to interpret with...

It’s very likely I’ve confused some things here and am really not sure how much this all stands up, I’m less proposing a definite mechanism as getting an idea of what potentials (hah!) there are here. But they tell a story of how proteins are reused for different purposes and the same ion...

A couple more papers https://pmc.ncbi.nlm.nih.gov/articles/PMC9409431/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5833991/ https://pmc.ncbi.nlm.nih.gov/articles/PMC3973911/ https://pubmed.ncbi.nlm.nih.gov/41459943/ (unfortunately no full text for this one but it looks interesting)

So from more reading, KCNC2 is part of the Kv3 family while KCNIP4 is a subunit of the Kv4 family, so don’t directly interact. But they do form parts of the same network so effects could compound. And DPP3 and DPP6 which were also identified as relevant in the PrecisionLife analysis can have a...

Yes, worse or at least more noticeable the worse I am. When I’m at my best I’m not very aware of it but it is still there. Given I spent time with unprotected ears in loud places (clubs and music venues with big speaker systems and motorsport events) it wouldn’t be surprising if I had it anyway...

PrecisionLife highlighted the following, AIUI their pipeline sometimes showed things differently partly due to their method but also differences in QC/cleaning of the raw data. KCNIP4 (beta subunit which modulates the activity of Kv channels) This showed up in the brain/neuron/glutamate cluster...

Some more a reading on voltage gated potassium ion channels and involvement with neurological and psychiatric conditions, it seems an area of interest Voltage-gated potassium channels as a potential therapeutic target for the treatment of neurological and psychiatric disorders, 2024, Faulkner...

Source

This is dense and tbh I’m not sure how intelligible to most of us let alone relevant. But I found it while looking at papers in this thread on voluntary and involuntary movements. Why post it? Well it seems to be predict dopaminergic effects on Kv4.2 in D1-MSNs. Kv4.2 being a potassium...

Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales—Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic Effects and Predict the Role of Kv4.2 Abstract The basal ganglia are involved in the motivational and habitual control of motor and...

Thanks @Andy this looks really interesting, looking forward to it. I assume it will be recorded and made available after? Is this looking at existing DecodeMe data or looking forward to SequenceME? I’m sure we all have a lot of questions on both. On existing data it would be interesting to hear...

Just got to the whole video. Thank you so so much for this, it's always so inspiring to hear @Chris Ponting speak, he is such a great scientist and communicator. We’re lucky to have him and the group he’s built with others. The project ofc sounds really interesting and @dave30th does a great...

I guess it is fair to say there is no evidence for complete rest. But in the wider context the tone seems standard NHS ‘assume the patient is lazy’ stuff which completely ignores the reality of severe me/cfs and lack of any specialist services for severe patients it signposts. Fine for keeping...