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Metabolic Trap, wouldn't we suffer from serotonin abnormality?

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Wishful

Senior Member
Messages
5,751
Location
Alberta
It's possible that I'm misinterpreting my observations, but an increase in cerebral TRP seems to make my symptoms worse, and IFN-g does so in a similar way, so I still believe that I'm overconverting TRP into the nastier kynurenines.

Does anyone here know whether the research into IDO1&2 was done on cerebral cells (microglia) or just on regular tissue cells? I believe that the core ME problem is inside the BBB, and all the other ME issues in the body are secondary.
 
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wigglethemouse

Senior Member
Messages
776
Wishful said:
Does anyone here know whether the research into IDO1&2 was done on cerebral cells (microglia) or just on regular tissue cells?
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HealthRising: The Metabolic Trap Shines During the Symposium on the Molecular Basis of ME/CFS at Stanford
The group wasn’t sure if the trap even existed in the immune cells they were testing. It might have been only present in other cells.
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The Trap certainly highlighted how effective Working Groups can be. Different members offered to produce models of the trap were offered up. Among other things, those models will be able to provide ways to demonstrate that the trap is present in brain serotonergic neurons and to test potential therapies.
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Research 1st

Research 1st

Severe ME, POTS & MCAS.
Messages
768
Anyone of you lovely people thought of being a pioneer and getting a SERT PET brain scan? Yes I know it's hard to obtain. :(

So for now let's pretend we had this opportunity and we all got tested...

Do you guys think it would show we have: low, normal or elevated serotonin? I'd love to know if this would help bolster the research the OMF have been doing.

Hope you're all hanging in there. :hug:
 
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FMMM1

Senior Member
Messages
513
Wishful said:
It's possible that I'm misinterpreting my observations, but an increase in cerebral TRP seems to make my symptoms worse, and IFN-g does so in a similar way, so I still believe that I'm overconverting TRP into the nastier kynurenines.

Does anyone here know whether the research into IDO1&2 was done on cerebral cells (microglia) or just on regular tissue cells? I believe that the core ME problem is inside the BBB, and all the other ME issues in the body are secondary.
Click to expand...

They used peripheral blood mononuclear cell (PBMC); just Google that and you'll find out what these are. It's a blood test i.e. using readily accessible sample type. Problem with brain stuff is that you need cerebro spinal fluid. Most of the tersting (nano needle, seahorse, --) uses PBMC; check out Ron's talk at the 2018 Community Symposium.

Brain stuff is difficult; limited amount you can measure with scans e.g. inflammation (microglia) etc.
 
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andyguitar

Moderator
Messages
6,610
Location
South east England
As has been pointed out by @Horizon the fact that 40% of the population have this mutation does raise some questions. Earlier this year there was some research from Japan that was re-published. If I remember correctly it was found that sufferers had a lower density of the Serotonin transporter SERT. @Research 1st maybe interested to know that the SERT abnormality was detected using a PET scan (probably- not had time to check the research!) What we maybe seeing here is 2 problems that come together and create symptoms. The IDO1 and 2 defect combined with either a genetic or acquired defect with SERT. I have long suspected that Serotonin was heavily implicated in causing symptoms. If it turns out to be something along these lines then are we to suppose that ME/CFS is a metabolic disorder?
 
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FMMM1

Senior Member
Messages
513
andyguitar said:
As has been pointed out by @Horizon the fact that 40% of the population have this mutation does raise some questions. Earlier this year there was some research from Japan that was re-published. If I remember correctly it was found that sufferers had a lower density of the Serotonin transporter SERT. @Research 1st maybe interested to know that the SERT abnormality was detected using a PET scan (probably- not had time to check the research!) What we maybe seeing here is 2 problems that come together and create symptoms. The IDO1 and 2 defect combined with either a genetic or acquired defect with SERT. I have long suspected that Serotonin was heavily implicated in causing symptoms. If it turns out to be something along these lines then are we to suppose that ME/CFS is a metabolic disorder?
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I'm guessing here. If you check out Ron Davis's, and Robert Phair's, talk at the 2018 symposium then I think you'll find that Ron/Robert discuss serotonin levels in cells. Ron/Robert mention that serotonin may be high/low and the cell will have adapted to this level of serotonin. Would the level of serotonin transporter change to reflect this altered serotonin level? @JaimeS posted recently about having a low level of serotonin transporter.

Interesting that the "density of the Serotonin transporter SERT" can be measured using PET.
 
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FMMM1

Senior Member
Messages
513
Wishful said:
Well, the research doesn't mention microglial cells being tested, but since those cells do produce IDO, it's likely that a genetic defect would affect them.
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Yea if you check out the 2017 OMF symposium presentations you'll see one on activated microglia. Also, the PET study (5 years ago?) by researchers in Japan showed activation of microglia in people with ME/CFS.
 
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andyguitar

Moderator
Messages
6,610
Location
South east England
Suprising this thread has'nt had more attention. If they have'nt seen it yet i expect @Gondwanaland , @blueberry , and @ljimbo423 would find it interesting. For members who could afford it, looking for abnormalities in the SERT gene may be helpful. The gene is SLC6A4. There has been much research into it. I note what @FMMM1 says about Ron/Robert looking at Serotonin in cells. What I am interested in is what effect Serotonin has when it is outside of a cell. What I am proposing here is that findings relating to it's level in a cell is of little interest. It's what happens when it is what could be described as "Free". I shall stick my neck out and say it may be creating Hydrogen Peroxide which causes inflammation. And this is the cause of symptoms.
 
bertiedog

bertiedog

Senior Member
Messages
1,743
Location
South East England, UK
andyguitar said:
looking for abnormalities in the SERT gene may be helpful. The gene is SLC6A4.
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I have just checked my results for this gene and I am homozygous for the following -

rs140701, rs2020942, rs2066713 and heterozygous for the following

rs1042173, 11080121, 12449783, 28914833

Have to be honest, I haven't a clue what this means but I know one of my reports say I have a problem with breaking down all the neurotransmitters.

Pam
 
ljimbo423

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
@andyguitar - I haven't done much research into the metabolic trap theory, so I really can't add anything to it.

My personal feeling is, the trap or IDO dysfunction is probably a downstream affect of increased intestinal permeability or "leaky gut".

Caused by immune system activation and the oxidative stress from it.
 
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andyguitar

Moderator
Messages
6,610
Location
South east England
HI @bertiedog if you want to see some genetic research into what genes could be used as a marker for CFS put this in your search engine PMID19772600 There is a lot there but just reading the conclusion might be interesting. Also worth a look is to see if anything is amiss with gene NR3CI on your results.
 
bertiedog

bertiedog

Senior Member
Messages
1,743
Location
South East England, UK
andyguitar said:
Also worth a look is to see if anything is amiss with gene NR3CI on your results.
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Have found this one now and doesn't look great for me, homozygous for 7 and 1 heterozygous with 17 normal. Many of the other ones I looked up in the PMD you quoted I have issues with too so looks like I seem to have at least some of the genetics that are mentioned that might be an issue.

Was particularly interested to see that regarding AMPD1 I had 3 heterozygous out of 6 and this is to do with excessive muscle fatigue which is exactly what I get!

Thanks for your interest.

Pam
 
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