Pre-print: Innate immune signaling & sex differences contribute to [..] impairment, neuroinflammation, & mitochondrial rewiring in [GWI], 2020, Bryant

Andy

Retired committee member
Full title: Innate immune signaling and sex differences contribute to neurocognitive impairment, neuroinflammation, and mitochondrial rewiring in a mouse model of Gulf War illness
Gulf War Illness (GWI) is a chronic, multi-symptom disorder affecting approximately 30 percent of the nearly 700,000 veterans of the 1991 Persian Gulf War. Recent studies have revealed that GWI-related chemical (GWIC) exposure promotes immune activation and metabolic rewiring, which correlate with neurocognitive impairments and other symptoms of GWI. However, the molecular mechanisms and signaling pathways linking GWIC to inflammation, metabolic alterations, and neurological symptoms remain unclear. Mitochondrial dysfunction has been documented in veterans with GWI and rodent models, and because mitochondria are key immune regulators, we hypothesized that alterations to mitochondria-immune crosstalk could contribute to the development of GWI-related symptoms.

Here we show that acute exposure of murine macrophages to GWIC alters mitochondrial respiration and potentiates innate immune signaling and inflammatory cytokine secretion. Using an established mouse model of GWI, we report that neurobehavioral changes, neuroinflammation, and mitochondrial protein rewiring are attenuated in mice lacking the cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) and NOD-, LRR- or pyrin domain-containing protein 3 (NLRP3) innate immune pathways.

Finally, we report sex differences in response to GWIC, with female mice showing more pronounced cognitive impairment, neuroinflammation, and mitochondrial protein alterations in the brain compared to male mice. Our results provide novel information on sex differences in this model and suggest that STING and NLRP3 are key mediators of the cognitive impairment, inflammation, and mitochondrial dysfunction observed in GWI.
https://www.biorxiv.org/content/10.1101/2020.08.28.271833v1
 
I simply cannot understand, and never will, why people do not understand that all of these mysterious diseases are druven by dysfunctional mitochondria.

I mean in me/cfs this should be seen as quasi factious until there is 100% proof for it because it is so unbelievably obvious and everything points in that direction for gods sake.

Is it not obvious that when you do not have enough energy that you do not produce enough?

WE ARE NOT TALKING ABOUT FATIGUE BUT LACK OF ENERGY IN ME/CFS!

It would be nice and timely if scientists and doctors start to recognize this.

The reason we know so little about me/cfs is that we know so little about how to identify malfunctioning mitochondria in diverse tissue. 99% (my personal experience) of doctors still believe you can not have a mitochondrial disease without raised lactate.

Everything, I mean really everything screams: MITOCHONDRIA.

People still look at cytokines for f*** sake!
 
Is it not obvious that when you do not have enough energy that you do not produce enough?
No, it is not obvious.

It is empirical clear that drugs can change the feeling of "having energy" or "not having energy".

And only because there isn´t any drug that has been found to influence any fatique-feelings in CFS on any longer run, this doens´t mean that there is really no energy.

The feeling of no energy can have a lack of something at any place in the row (say in the muscles, in the nerves, in any special parts of the brain, or whatever).
 
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No, it is not obvious.

It is empirical clear that drugs can change the feeling of "having energy" or "not having energy".

And only because there isn´t any drug that has been found to influence any fatique-feelings in CFS on any longer run, this doens´t mean that there is really no energy.

The feeling of no energy can have a lack of something at any place in the row (say in the muscles, in the nerves, in any special parts of the brain, or whatever).


crazy talk. people keep doing that.

if you just feel fatigued, I guess you could go for a 10 k run, right?

If the actual energy is no issue there is absolutely zero risk whatsoever for you to do just that.

It does not matter because you just FEEL you have no energy.
 
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If the actual energy is no issue there is absolutely zero risk whatsoever for you to do just that.
No, for example, you might miss-wire you nerves.

The machinery of feeling could be ill. And the worse you would make it, the more difficult would it be to reverse it.
 
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