Peripheral neurons, CRH, and sickness behavior

Though to your general point @Hutan about some negative feedback loop being at play here with the ME/CFS autopsy findings, I do think that has a good chance of being relevant. I’ve posted earlier in this thread that there are known mechanisms of regulating CRH production within a cell—the more stimulation it receives to produce CRH, the more the suppression mechanism ramps up. So if we’re thinking that the findings of reduced CRH in severe ME/CFS autopsies are because of some negative feedback, I think that does end up being helpful. Because it tells us that the specific CRH+ population looked at in the autopsy studies is affected. So either the problem starts at these CRH neurons, or theyre one of the brain regions receiving continuous input from somewhere else.

In which case it might be useful to look at this other CRH+ population in the BNST. Maybe the brain stem as well. If those are also depleted, it would tell us that the problem probably isn’t starting in any of those brain regions, but somewhere upstream that relays to all of them. Which would probably be either the dorsal root ganglion, or actual immune signaling somewhere. That might be something the Netherlands team would be interested in, though I think funding is going to be the most immediate hurdle for them to pick up new questions.

Edited to fix a typo
 
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Yes, agreed. There is CRH production outside the hypothalamus eg Wikipedia:
In addition to the hypothalamus, CRH is produced by neurons in other brain regions, including the neocortex, limbic system and brainstem. In the olivocerebellar tract, CRH is expressed in neurons that send their axons from the inferior olivary complex to the cerebellar cortex. CRH is also synthesized in peripheral tissues, such as T lymphocytes, and it is highly expressed in the placenta, where it regulates the length of gestation and the timing of parturition and delivery.
Click to expand...

Just noting for anyone looking up 'BSNT' that it's 'BNST'.
'bed nucleus of the stria terminalis'
(I've remembered it from a paper because I thought they were talking about 'brainstem' for a bit, and it's not.
 
Hutan said:
Yes, agreed. There is CRH production outside the hypothalamus eg Wikipedia:


Just noting for anyone looking up 'BSNT' that it's 'BNST'.
'bed nucleus of the stria terminalis'
(I've remembered it from a paper because I thought they were talking about 'brainstem' for a bit, and it's not.
Click to expand...
CRH is synthesised in T Lymphocytes? That's interesting if its not Wikipedia telling porkies.
[Edit: found this paper https://www.sciencedirect.com/science/article/abs/pii/016557289390262W]

Lots of interesting brain regions to look into too. We haven't seen the full CRH autopsy paper yet have we?
 
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