Could this be a hidden key to ME? How a Brain Area Implicated in Alzheimer’s May Be Vulnerable to Degeneration

[YippeeKi YOW !!]

At first glance this article would seem to be way off-base for ME, but when I read the following paragraph, I decided that it would be worthwhile posting if for the science-oriented members to take a look at and see what they think. I know what I do.

“A specific genetic mutation is implicated in a rare, neurogenetic disorder called
GPT2 Deficiency—a genetic syndrome that the Morrow lab first reported in 2016.​

The gene of interest is called GPT2 (Glutamate Pyruvate Transaminase 2),
and it generates an enzyme that is vital to metabolic pathways in
mitochondria, the energy centers of cells.”

​

How a Brain Area Implicated in Alzheimer’s May Be Vulnerable to Degeneration
https://neurosciencenews.com/lc-neurodegeneration-21346/

​

 

[YippeeKi YOW !!]

Let me explain ....

Some time back, I floated my observation that for some reason, a disproportionately large number of members here found that they were sensitive to glutamate, and had experienced varying degrees of reactions to it ranging from the mild to the more pronounced, a statement that met with, shall we say, a mixed response. Some members dismissed it out of hand, but others, who'd experienced that response themselves, agreed.

Which is why the article caught my attention. Glutamate-pyruvate transaminase is a blood enzyme
that is vital to metabolic pathways in mitochondria, the energy centers of cells, as stated in the article.
It also metabolizes the glutamate in blood, resulting in low extracellular levels of brain glutamate,
and in its absence, a serious overload of glutamate could ensue. Which might explain some of our reactions to exogenous glutamate.

I can see that a lot of you are taking a quick look at the thread, probably skipping the article, and moving on. Please give it a look. It's not the dead end, off-topic load o'crepe that it might appear to be .... at least it doesnt seem so to me. WHich is why I posted it. More and better, more sciencey-based, opinions are needed.

The article goes on to state:

"The GPT2 enzyme regulates neuronal growth through replenishment of
tricarboxylic acid cycle intermediates and the modulation of amino acid metabolism."​

This might explain why BCAA's have helped quite a few members here, improving their base levels and QOL, since they metabolize slightly differently than other proteins and may sidestep the need for the GPT2 enzyme, but that's just a poorly informed guess ...

"Because of the focus on the locus coeruleus in the development of drug treatments,
Morrow said this finding about the early impairment of this brain region
will have interest to a broad range of people in the neuroscience
and neuropsychiatric community."
​

.... but apparently not to too many in the PR community, even tho many of us have stated that the answer, when it comes, will almost doubtlessly come from left field, form some area that wasnt aimed specifically at our illness but that nonetheless provides a critical connecting link ...

EDIT ... for more clarity and several typos .... what a surprize ....

 

[Rufous McKinney]

I hope to read it. It sounds important. It just a scheduling and how long are the paragraphs, exercise.

Don't we have some big deal problem with pyruvate? maybe its a different pyruvate spot. I'd go wander out and query, but queries are off line.

too many queries yesterday. More vague today.

BCAAS seemed to help me some. I am off that, off most everything, for a long time now....I get the stomach stuff and off the protocols I go for months at a time...

 

[Rufous McKinney]

Don't we have some big deal problem with pyruvate

its pyruvate dehydrogenase....over in the mitochondria...we have issues there, too.

 

[Wishful]

ME doesn't seem to be degeneration, since it can switch out of the ME state so rapidly and completely. Glutamate doesn't bother me, and BCAAs don't affect my ME symptoms, so count me as counterevidence.

 

[Judee]

how long are the paragraphs

Same. Can't do long or wide right now. Brain protests.

 

[YippeeKi YOW !!]

I hope to read it. It sounds important. It just a scheduling and how long are the paragraphs, exercise.

It's short paragraphs, a pretty easy read if you dont need to understand all of the science terms. You can skip the far denser and harder to read study attached at the bottom of it, or you can skip it altogether and just trust my chosen quotes and spit balling of possible connections to ME. It's conjecture and dot-connecting, not particularly scientific.

But it's not like it's going to disappear at midnite like Cinderella's pumpkin coach, so please PLEASE dont pressure or stress yourself. It'll be here later ...

@Judee ... Im so sorry that you're both under the weatherish. I'm just clawing my way out of a nearly 2 week down-spike that was really miserable and fervently praying that it's over, so my heart goes out to you

 

[YippeeKi YOW !!]

ME doesn't seem to be degeneration, since it can switch out of the ME state so rapidly and completely. Glutamate doesn't bother me, and BCAAs don't affect my ME symptoms, so count me as counterevidence.

I wasn't referring to permanent degeneration, altho some cases of ME seem to qualify, but rather to the hints in the article that what contributes to, or even causes, other diseases might have a hand in our own.

If you have some easy references or links to the " ....switch out of the ME state SO RAPIDLY AND COMPLETELY....", it would be heartening to see them. I haven't bumped into anything but the slow slog up, down, up, down down, up, up, down down down down, up slog out of this morass ....

I did a quick site search for 'glutamate' and THREE FULL PAGES of posts popped up, so you can count yourself in the lucky column. Not something any of us get to do too often ....

 

[JES]

Getting a bit off topic, but there have been quite a few stories about temporary remissions, although they are quite buried somewhere in this information space. Quite a few people, even some severe patients, have reported temporary large improvements following Abilify, although it seems the more severe you are, the harder it is to find anything that works. Here is a recent one of somebody describing a full remission long ago following colonoscopy:

https://forums.phoenixrising.me/threads/temporary-improvement-after-colonoscopy.83269/

It seems that people fall into different categories. Some being very sensitive to supplements and some not reacting to anything. I think the first category might have more success finding (temporary) remissions. I belong to the first category, but unfortunately the improvements are always transient. Here is a list of things that helped me achieve some form remissions:

-Catching a cold. This is the best working one for me, but unfortunately I wasn't lucky enough to catch one since 2016. Ever since my ME/CFS symptoms started, I also seem to almost never get acutely ill.
-Brain MRI. This is a bit sketchy as I only did it once, so could have been some other factor involved, but it produced a great temporary improvement that lasted for 24 hours.
-Sleep deprivation. Not as complete as above, but still gave me let's say 50% improvement. Nowadays a bit less.
-VNS stimulation. This also gave what I thought was a cure, but then stopped working the next day.
-Switching in and out of ketosis, it seems my body gets fooled to work normally for a while.
-Alcohol. Very temporary, but following consumption of more than 2-3 portions, I usually feel better at some point in the next 24 hours.
-Certain drug and certain antidepressants. The remission only lasts a day or sometimes even less.
-Constipation. Weird one, but seemed to produce some improvements last time.
-Certain changes of environment or traveling have triggered weird improvements, but don't seem 100% replicable.

 

[Rufous McKinney]

But it's not like it's going to disappear at midnite like Cinderella's pumpkin coach,

well, my best intentions have a way of sometimes being forgotten, altho I do manage to slightly keep track of things like: try to read THAT. But don't forget how to find the THREAD.

There is an opportunity to devise a new notebook tracking scheme. Current notebook became chaotic.

 

[Rufous McKinney]

Catching a cold.

I got a cold for two days (took the chinese don't get sick pills) March 2018 while foreign traveling.
I think our exposure to germs is affected by our isolation.

Sharing I had a seven day intense gastroperesis flu, which results in my intestines being starved for about a week. I then experience nearly normal bowel activity, for about a week. Then, it reverts to the IBS confused state that is normal.

My ME symptoms tend to intensify hugely during these events. That when I might die of air hunger. Or everything is so swollen up I can't swallow. But other sort of classic ME symptoms- well maybe I am just ignmorig them due to teh misery, then later they gradually re-occupy the attention units.

 

[Rufous McKinney]

like Cinderella's pumpkin coach

I waded through that...I used to tell people I took Evelyn Woods reading dynamic course (I could read REALLY FAST). Wonder what happened?

This paper contains considerable info on ME CFS and the anatomy of the locus coreolus ...however that is spelled.

Review of the Midbrain Ascending Arousal Network Nuclei and Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and Postexertional Malaise (PEM)
James N. Baraniuk

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870178/

From the abstract:

"The nuclei of the ascending arousal network were addressed. Midbrain and isthmus nuclei participate in threat assessment, awareness, attention, mood, cognition, pain, tenderness, sleep, thermoregulation, light and sound sensitivity, orthostatic symptoms, and autonomic dysfunction and are likely to contribute to the symptoms of postexertional malaise in ME/CFS and GWI."

A whole lot of important info about this brain anatomy is in the review article.

so now I'll hope for help Translating.

 

[Wishful]

I did a quick site search for 'glutamate' and THREE FULL PAGES of posts popped up, so you can count yourself in the lucky column.

The article is about glutamate in the brain. That wouldn't--unless the individual has a BBB disorder--involve sensitivity to dietary glutamate, since glutamate doesn't pass the BBB.

If you have some easy references or links to the " ....switch out of the ME state SO RAPIDLY AND COMPLETELY....", it would be heartening to see them.

Sorry, just personal experience. It does seem like flipping a switch: ME on/off. I triggered on several seemingly unrelated chemicals, so it's not just one pathway. Sadly, the chance of triggering a temporary remission seems to decline over time; I had several in the first month or two, another two in the first few years, and another one a few years after that, but I haven't had one in 10+ years now. So sad.

BTW, none of my temporary remissions were predicted in advance. They were totally unexpected effects while trying things that might provide some reduction in my symptoms, or just something new in my diet.

 

[hapl808]

The article is about glutamate in the brain. That wouldn't--unless the individual has a BBB disorder--involve sensitivity to dietary glutamate, since glutamate doesn't pass the BBB.

I think there's a good chance many of us have BBB disorders. I've heard for years things like MSG can't have negative effects as it's just dietary glutamate, yet it would put me in bed for weeks. I've tried low glutamate diets and they're somewhat helpful. Not a huge difference, but seems noticeable. Why? No idea. There's some research on Gulf War Illness that also seems to show benefit with a low glutamate diet, but not sure how robust the data.

I think we just don't really understand what's going on. Maybe BBB disorders are a common element of ME/CFS or MCAS or whatever. Or maybe they're not. No idea.

BTW, came across some note I had from a book where it was comparing cumin's effect to aspirin which I thought was interesting.

 

[Rufous McKinney]

I think there's a good chance many of us have BBB disorders.

its all leaking. (my theory)

I've gotten very noticeably glutamate sensitive over the last two years.

 

[YippeeKi YOW !!]

The article is about glutamate in the brain. That wouldn't--unless the individual has a BBB disorder--involve sensitivity to dietary glutamate, since glutamate doesn't pass the BBB.

Sorry @Wishful, I missed this response and didnt get an alert ....

While glutamate may or may not cross the BBB (several sources state that it does, altho one NCBI study states that that is a tacit assumption, based on the nature of the transport system), GLUTAMINE easily crosses that barrier, and glutamine is the precursor to glutamate, and is converted by the brain into either GABA or glutamate, depending on numerous factors. A dysregulation in that assessment/conversion process would allow glutamine or glutamic acid to be automatically converted to glutamate, bypassing the need for GABA, no matter how exigent that need may be.