Bone, not adrenaline, drives fight or flight response

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"Mediation of the acute stress response by the skeleton," Cell Metabolism (2019). DOI: 10.1016/j.cmet.2019.08.012 , https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30441-3

Mediation of the Acute Stress Response by the Skeleton
Author links open overlay panelJulian MeyerBerger12GerardKarsenty19
https://doi.org/10.1016/j.cmet.2019.08.012Get rights and content
Highlights

The ASR stimulates osteocalcin release from bone within minutes


Glutamate uptake into osteoblasts is required for osteocalcin release during an ASR


Osteocalcin inhibits the parasympathetic tone during an ASR


In adrenal insufficiency, increased osteocalcin levels enable an ASR to occur

Summary
We hypothesized that bone evolved, in part, to enhance the ability of bony vertebrates to escape danger in the wild. In support of this notion, we show here that a bone-derived signal is necessary to develop an acute stress response (ASR). Indeed, exposure to various types of stressors in mice, rats (rodents), and humans leads to a rapid and selective surge of circulating bioactive osteocalcin because stressors favor the uptake by osteoblasts of glutamate, which prevents inactivation of osteocalcin prior to its secretion. Osteocalcin permits manifestations of the ASR to unfold by signaling in post-synaptic parasympathetic neurons to inhibit their activity, thereby leaving the sympathetic tone unopposed. Like wild-type animals, adrenalectomized rodents and adrenal-insufficient patients can develop an ASR, and genetic studies suggest that this is due to their high circulating osteocalcin levels. We propose that osteocalcin defines a bony-vertebrate-specific endocrine mediation of the ASR.


Bone, not adrenaline, drives fight or flight response
September 12, 2019 , Columbia University Irving Medical Center
https://m.phys.org/news/2019-09-bone-adrenaline-flight-response.html

But a new study from Columbia researchers suggests that bony vertebrates can't muster this response to danger without the skeleton. The researchers found in mice and humans that almost immediately after the brain recognizes danger, it instructs the skeleton to flood the bloodstream with the bone-derived hormone osteocalcin, which is needed to turn on the fight or flight response.
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A series of studies since then have shown that osteocalcin helps regulate metabolism by increasing the ability of cells to take in glucose, improves memory, and helps animals run faster with greater endurance.
 
Exciting stuff, at least intrinsically. It's new to me - to the better informed?

Spans a range of topics related to ME, at least tangentially. Seemed interesting to flag for those better equipped to comment.

A question I would have is whether the post viral element of ME would be incompatible with this phenomenon having a role in ME? And if not, could chemical, allergic or other osteo responses have similar effects.

I'm sure others will have better Qs.
 
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I would imagine that most vertebrates that have had their skeletons removed do not exhibit any stress reactions, afterwards.

This could be seen as evidence that a skeleton is necessary for such a response.

As to the idea that the stress response is influenced by the skeleton, I have no clue.
 
What it shows is that basic physiology of mammals is completely known. It may be a long time before the relevance to ME treatment can be worked out, but it gives the lie to medically unexplained as if everything was already discovered.
 
Tagging @Jonathan Edwards

V interested in what is speculatable as reasonable initial testable hypotheses wrt this and ME.

I don't really get what they are getting at. Presumably sharks have fight and flight responses but they don't have any bones.

We fight or fly long before these hormones get going. OK the body readjusts its physiology, but loads of factors contribute to that. The fact that adrenalectomised animals have the response seems to me not very surprising since they still have adrenergic neurons.

Not sure how it would relate to ME.
 
I don't really get what they are getting at. Presumably sharks have fight and flight responses but they don't have any bones.

We fight or fly long before these hormones get going. OK the body readjusts its physiology, but loads of factors contribute to that. The fact that adrenalectomised animals have the response seems to me not very surprising since they still have adrenergic neurons.

Not sure how it would relate to ME.
Many thanks for the gut response - invaluable.

In terms of ME relevance, it was limited to my mind extrapolating potential and wanting to flag it for more expert imagination :)
 
I am not an expert so i cannot make any connections, but i am really curious to know if you believe that high levels of stress affect negatively your ME symptoms.
 
For what it is worth, high levels of stress make my me feel better. I believe that I work on adrenalin (or something, it would be good to have it tested). When I first read about this idea it explained many things about my illness I could not work out before.

I was once in bed feeling too sick to do anything when I realised my mother in law had left my 2 year old escape artist in the front garden of our house on a road with steady traffic. I was downstairs and grabbing him before I had time for thought.

When my mother was dying I managed to hold things together for almost 3 months. I would not have manage to visit every day for much longer and was getting sicker but still.

I did deteriorate at a time of constant worry with problems pressing on all sides but I think that was more because I could not sleep. Usually it is the physical effort which determines how much I can do.
 
The balance between the three types of energy impact does definitely vary for me, and presumably across people too. I am also pretty sure that, for me, cumulative adrenaline does come with a come down eventually. It's a function of too many things to even be sure something is, or isn't, a problem sometimes. With different delays for each of them also. So I'm v careful in what I assume tbh
 
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I waited over a year for my PIP Tribunal, this was incredibly stressful for me. During that year I had suicidal ideas, not something that I had prior to the longstanding stress over Tribunal. Once Tribunal over, with a very positive result for me, I was totally exhausted. That exhaustion lasted for well over a year, nearer two. (Missed over 2 years of my grandkids' lives and fun with them as just too flattened. :cry:)

Suspect it's the ongoing stress of a situation like that, that you have no control over is the problem. Research does support control being important in stressful situations. OK, that's work place stress, but I don't see that as being different to general life stress for people who aren't in work.
 
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