An Excellent Explaination of How SSRI's Inhibit Sert

This is a place to post research you have done on the topic along with your conclusions.
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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MisterCharlie wrote: Fri Jan 21, 2022 6:24 pm
Tree wrote: Wed Jan 19, 2022 3:03 am
We want to try to activate wnt in the brain, particularly in the dorsal raphe, but can't find anything that does yet. I'm going to microdose simovastin when it arrives which will probably be sometime later this month or February. It activates wnt in the hippocampus in mice so it might activate in the raphe too. Who knows. It's worth a try. "Moreover, simvastatin can promote Wnt/β-catenin signaling in the hippocampus of adult mice, and enhance neurogenesis both in cultured adult neural stem cells and the mouse hippocampus".


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894260/
Thoughts?

https://pubmed.ncbi.nlm.nih.gov/8131066/
Myo-inositol reduces serotonin (5-HT2) receptor induced homologous and heterologous desensitization
I think the cause of pssd is loss of sert functioning which desensitizes 5ht1a receptors. There's too much serotonin concentrated in the dorsal raphe like mentioned in the report. I also crashed hard from a 5ht1a agonist so I know it's the 5ht1a receptor that's become significantly desensitized, especially for people suffering from extreme symptoms.
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by Tree »

Pkc, pla2, and pka activation desensitizes 5ht1a receptors and wnt/b inhibition blocks sert. I'm looking to find drugs/supplements that target and reverse these pathways. So far I've found vitamin e inhibits pla2 and pkc. Aspirin is a pka inhibitor. Simvastatin activates wnt/b.
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by Tree »

"In mice, chronic treatment with the SSRI fluoxetine (Prozac) increases miR-16 levels in serotonergic raphe nuclei, which reduces SERT expression." We need to activate wnt/b and decrease miR-16 expression in the dorsal raphe to reverse permanent sert inhibition caused by ssri.

https://www.jstor.org/stable/40803108
Answers
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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I don't know if it's that simple unfortunately because there are studies claiming it increases beta catenin instead. Plus there are more micro RNA impacted.
How does it change the micro RNA I wonder though? Is it all through beta catenin?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877532/
ryjoseph97
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by ryjoseph97 »

I think downregulation of sert could also be the cause for chronic serotonin syndrome, which I believe I have. There is new research coming out about this syndrome. But no one has investigated the mechanisms yet.

https://neurologyindia.com/article.asp? ... st=Prakash

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040149/
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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Answers wrote: Mon Mar 21, 2022 10:20 am I don't know if it's that simple unfortunately because there are studies claiming it increases beta catenin instead. Plus there are more micro RNA impacted.
How does it change the micro RNA I wonder though? Is it all through beta catenin?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877532/
I think it might be.. but the difficult part is figuring out how exactly and if it's reversible. There are dozen of other downstream effects from silencing sert but it's definitely the root cause of pssd in my opinion. It explains too why I crashed from a 5ht1a agonist and suffered serotonin syndrome. It explains why I haven't gotten any better and dozens of others on this forum. It also explains why I'm hypersensitive to every substance on earth.

"Fluoxetine increases miR-16 levels in raphe by antagonizing canonical Wnt signaling"

https://www.researchgate.net/figure/Flu ... 3_46288449
Tree
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by Tree »

https://www.frontiersin.org/articles/10 ... 00091/full

From a mechanistic point of view, the rise of miR-16 induced by fluoxetine in serotonergic neurons results from an increased maturation of pri/pre-miR-16 through a GSK3β-dependent process.
GIXXER
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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lots of youtube vids as well

https://youtu.be/iRs9tbUAHAc
Maxin
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

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Tree wrote: Mon Dec 13, 2021 2:45 pm
Answers wrote: Mon Dec 13, 2021 6:55 am The question is how do you increase WNT signalling and suppress mir-16?
Exactly, Simvastatin increases sert via wnt signalling independent of cholesterol lowering effects. It makes me very eager to try. We all need to research and find wnt activators.
I tried it last year. The reason being it’s cured a few people from cfs by accident. I noticed some really amazing reversal of things for the first few days but then made me worse. Got scared and stopped
pssdperson
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Re: An Excellent Explaination of How SSRI's Inhibit Sert

Unread post by pssdperson »

Tree wrote: Fri Dec 10, 2021 6:23 am Pssd suffers from France should try to contact the author. She seems to be knowledgeable of how ssri's affect the serotonin transporter. It would be interesting to know if she has any updated information, aware of pssd, and opinions on it.

https://t3s-1124.biomedicale.parisdesca ... ne-baudry/
Has anyone tried contacting her? I’m not from France but I could email her
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