An Adrenalectomy Mouse Model Reflecting Clinical Features for Chronic Fatigue Syndrome, 2020, Lee et al

Another dubious mouse model, this time from Korea.

Open access, https://www.mdpi.com/2218-273X/10/1/71

 

Cut, cut, cut. NO WAY.

Why would you want to activate astrocytes and transforming growth factor beta (TGF-β) ?????

Ain't astrocytes not already activated in ME patients?

 

Yes, but what will that tell????

 

They are saying that removal of adrenal glands appears to create an illness that is closer to ME/CFS than the illness created by injecting mice with compounds that the immune system interprets as bacterial and viral infection.

Of course adrenal insufficiency is not ME/CFS and mice are not humans but I thought this was interesting.

 

Yes, but I do not see what it can tell.

Why create an Addison-patiënt? Addison is very difficult to control.

 

Adrena glands have a7nach receptors.

 

This has reminded me of this radio show that was posted here a couple of weeks ago about Doug Lindsay who came down with a sort of M.E like illness, after his mum and aunt had suffered for decades, and pretty much self diagnosed and got someone to do surgery on his adrenal glands. https://www.bbc.co.uk/programmes/p07xpjb9

 

An idea that came to me in the days when I gave up animal model work was:

If there are 100 models of illness X, each based on a different causal mechanism, then 99 of them must be the wrong mechanism. That makes it statistically highly likely that 100 of them are the wrong mechanism.

 

I think its a bit premature to do these kind of animal studies. We don't know if hypocortisolism really has something to do with the pathology of ME/CFS or if its just a consequence of it and findings for TGF beta are rather conflicting. So I don't think these could be seen as indicators wether an animal model resembles ME/CFS or not.

It thought it was interesting that they thought the immune model (injecting mice with compounds that the immune system interprets as bacterial and viral infection) looked more like depression than CFS, cause this theory is quite popular among CFS researchers. Then again I'm not sure if the tests they made the mouse do would be able to show a clear difference between depression or CFS. If mise can have CFS, i think they would look pretty depressed.

 

Isn't that going to be true of any models for illness X, animal models or otherwise? Presumably research is primarily about trying to find the right illness model, even if it turns out to be the 999th, whatever? (I suspect I may be missing your point here).

 

Feeds into the cortisol resistance narrative ? @alex3619

 

I haven't seen any followup published on the beta cortisol receptor problem. I think the researcher retired though. So many lines of research need to be solidly established or disproved. Its not happening fast enough.

 

Several years ago I felt so horrible and I begged my dr to ‘do something’. She is a bunch of blood tests, one of which was the AM and PM cortisol. It came back flagged at a critical low. Something like 45 when the normal range would be 180-800. I was sent to the endocrinologist, which was delayed because of the holiday season, but in the meantime was started on Cortef, which did not seem to do anything for me. Usually people feel a little jolt (a burst of energy) when given cortico-steroids. Not me. A month later, i had my consultation. My AM Cortisol still flagged as critical low, though a bit higher this time in the 80’s, i still did not feel better. I had the Corticotropin stimulation test (not sure if it’s the right name for it) which showed i did not have Addison. I was (very painfully) weaned off the Cortef and that was that.

i would welcome animal study of the Korean kind, because I believe the HPA axis hormones are involved, but with the caution that it may represent a subset of the patients and that it may explain one event in time, without explaining all of the symptomatology.

 

If there was only one, or maybe three models based on different causal mechanisms then the chance that one of them was the right mechanism could be fair. The only model for tuberculosis was injecting animals with Mycobacterium tuberculosis - and that turned out to be the right model.

But if there are 100 models each based on a different explanation then it looks very much as if people are struggling.

As an example, animal models of rheumatoid arthritis included immunising mice with cartilage collagen, immunising rabbits to milk by diet, injecting mycobacterial cell wall into rats, introducing trangenes encoding for absence of lymphocyte death in mice, intruding transcends for unregulated secretion of TNF, injecting mice with pristine oil, injecting ovalbumin into rat knees, and so on... None had any relevance at all to the aetiology of the illness (except that TNF turns out to be involved for other reasons).

 

I suspect that feeling horrible when waking up might could have something to do with cortisol awakening response not working well. By the time blood is typically drawn, the cortisol levels would however already be fairly normal.

I did a diurnal salivary cortisol curve once and the first sample in the morning was well below the norm.

 

They remove the whole glands. Look at all the things you have to compensate for.

 

Not exactly high on the "all other things being equal" scale.