Insular cortex neurons encode and retrieve specific immune responses, 2021, Tamar Koren et al.

Trish

Trish

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https://www.cell.com/cell/pdf/S0092-8674(21)01223-X.pdf
Research done in mice.

Highlights
  • Neuronal ensembles in the InsCtx are activated during peripheral inflammation
  • Reactivation of these neurons is sufficient to retrieve peripheral inflammation
  • These InsCtx neurons project to autonomic nervous system control sites (DMV, RVLM)
  • Inhibition of the InsCtx alleviates inflammation during DSS-induced colitis
Summary
Increasing evidence indicates that the brain regulates peripheral immunity, yet whether and how the brain represents the state of the immune system remains unclear. Here, we show that the brain’s insular cortex (InsCtx) stores immune-related information. Using activity-dependent cell labeling in mice (FosTRAP), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (dextran sulfate sodium [DSS]-induced colitis and zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Thus, we show that the brain can store and retrieve specific immune responses, extending the classical concept of immunological memory to neuronal representations of inflammatory information.
 
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I posted this because someone passed me a short article in today's inews newspaper where one of the researchers is quoted:

'Neuroimmunologist Professor Asya Rolls said: "It suggests the brain stores some representation of the inflammation". While offering the caveat that mice were not humans, she told the Times of Israel that it "opens up a new line of investigation for psychosomatic illnesses"
"I was surprised to see the effect so clearly with inflammation starting soon after the neurons were activated, even though there was no pathogen or other physical trigger."

She then suggests that if the brain can initiate inflammatory activity, then that might be useful in treating inflammatory conditions by finding a way to dial down the brain activity, instead of using immunosuppressants that leave patients vulnerable to other conditions.
 
It looks potentially very interesting.

I wouldn't call this a specific immune response, although it would be fair to call it a tissue-specific inflammatory response.

We already have evidence of something a bit like this in humans in terms of inflammation in one joint inducing symptoms in the mirror image joint on the other side. However, it is not clear that it has much real clinical significance.

If this was genuinely a 'psychosomatic pathway' it would be a commonplace observation that worrying about a particular part of the body made it swell up. In reality that does not happen, despite the fact that lots of people are very worried about bits of their bodies.

On the other hand this might be a cerebro-somatic pathway that our 'minds' have no access to, as for the hypothalamus.

I don't seem to be able to get the full text despite going through college e-journals. It may be available next week though.
 
I rather hoped that her reference to psychosomatic illnesses was to suggest that they may not be psychosomatic, in the sense of a result of wrong thinking or anxiety about symptoms recurring, but rather a way of showing they are not thought initiated, but brain initiated. Does that make sense?
 
Trish said:
I rather hoped that her reference to psychosomatic illnesses was to suggest that they may not be psychosomatic, in the sense of a result of wrong thinking or anxiety about symptoms recurring, but rather a way of showing they are not thought initiated, but brain initiated. Does that make sense?
Click to expand...
Trish said:
'Neuroimmunologist Professor Asya Rolls said: "It suggests the brain stores some representation of the inflammation". While offering the caveat that mice were not humans, she told the Times of Israel that it "opens up a new line of investigation for psychosomatic illnesses"
Click to expand...
I interpreted Rolls' quote as meaning "opens up a new line of investigation for otherwise-presumed psychosomatic illnesses".

So if I understand correctly, the suggestion is that a part of the brain stores immune response signatures of some kind, so that if faced with the same threat subsequently, then a look-up mechanism retrieves and applies the previously-learned immune response, without wasting precious time and energy relearning how to respond.

Presumably - and I appreciate this is all extremely tentative - this could go badly wrong, if the look up mechanism became unreliable, and an immune response learned from a previous infection, could instead be erroneously activated by a completely different and innocuous trigger. I suppose the lookup mechanism could get corrupted at any point after its data was stored, or it could even go wrong at the point of storing it. Once corrupted it subsequently then matches against the wrong trigger(s).
 
Yes, big problem is that the psychosomatic theories of illness are now embedded in sectors of psychiatry (consultation-liaison in Australasia) and in “popular” psychology, so basically society (and the wellness industry) and this is the language to explain MUS and ME/CFS.
 
This offers another possibility for chronic inflammation: those neurons might be maintaining the active state after the trigger has been removed. If you add in ME altering neural function, it could be locking us into a feedback loop, with the inflammation altering the neurons in a way that sustains the brain-initiated inflammatory response.
 
Sam Carter said:
Here's a linky to the preprint fulltext on bioRxiv: Remembering immunity: Neuronal ensembles in the insular cortex encode and retrieve specific immune responses.
Click to expand...

I am worried that this is all a bit too high tech and not very feet on the ground.
Inflammation was judged by complicated counting of immune cells. I would have preferred to see some old fashioned pathology actually showing inflammation. The gut is normally full of immune cells and counting cell populations using fluorescence is something easily skewed by enthusiasm and cherry picking.

But apart from that the procedures used to manipulate the neutrons are way outside anything physiological and pretty science fiction. If you mess around with transgenics long enough you are bound to find a model that will produce a result that seems to confirm your theories.
 
This to me sounds very exciting. I hope some me/cfs researchers can review this research and try to find a way if it is related to the underlying cause of me/cfs. For me I wonder if my first bout of ebv 15 years ago primed by brain to malfunction (ie these ‘memory pathways’) when i came across subsequent minor virus that triggered my me/cfs. This makes a lot of sense to me. Thanks for posting!
 
Merged thread

Article in Nature:

Inflammation in the gut is encoded by neurons in the brain

"The nervous and immune systems interact in a bidirectional manner. It emerges that inflammation in the body activates brain cells that, when later reactivated, can trigger a recapitulation of the inflammatory response"

Haven't got a link to the paper yet
[EDIT - @Andy post below seems to be paywalled]

"Interactions between the nervous and the immune systems have been a topic of great interest over the past few decades. Neuronal signals can affect immune functions, and immune cells can modulate the activity of neurons in the brain and spinal cord, or in the rest of the body (known as the periphery), in health and disease1,2. Writing in Cell, Koren et al.3 demonstrate that inflammation in the abdominal cavity results in the stimulation of certain neurons in a brain area called the insular cortex, or the insula.

The rest of the article is paywalled.
 
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