5-HT1A/Gene Coding related research - singlecell OP

[Moloch]

SingleCell on Fri Dec 12, 2014 10:58 am

Cell


1.
"We present evidence that by targeting specific transcription factors it may be possible to oppositely regulate 5-HT1A auto- and heteroreceptor expression, synergistically increasing serotonergic neurotransmission for the treatment of depression."
http://www.ncbi.nlm.nih.gov/pubmed/24180393 - 2014

2.
"These results suggest that the interaction between HTR1A+272G>A and 5-HTT VNTR is involved in the response to mirtazapine treatment and that a combination of these may be a useful marker for predicting treatment response to mirtazapine."
http://www.ncbi.nlm.nih.gov/pubmed/24911443 - 2014 Note: I don't see how this is any help, but interesting.


3.
"As regards the genes that influence the drug's pharmacodynamics, polymorphisms of SLC6A4, HTR1A and MAO-A seem to be involved in the response to fluoxetine, while the genes COMT, CRHR1, PDEA1, PDEA11 GSK3B and serpin-1 also seem to play a role."
http://www.ncbi.nlm.nih.gov/pubmed/22791347

4.
"We found that TSA did not antagonize the hypoxia-induced activation of D3 and D4 dopamine receptor genes, implying that induction of thesegenes is not mediated directly by hypoxia inducible factor-1alpha. On the other hand, TSA dramatically upregulated the expression of DAT and SLC6A4 (45-fold and 15-fold, respectively), while transcript levels of MAO-A and COMT were significantly reduced (by 70% and by more than 90%, respectively). Induction of DAT protein expression was detected by western blotting. These results suggest that inhibition of histone deacetylases might help restore presynaptic monoamine pools via suppression of catecholamine breakdown and facilitation of monoamine reuptake in neurons.

http://www.ncbi.nlm.nih.gov/pubmed/21785940 - Note: Restoring presynaptic ..pools.

5. "Extensive characterization of the transcriptional regulation of the 5-HT1A gene (HTR1A) using cell culture systems has revealed a GC-rich "housekeeping" promoter that non-selectively drives its expression; this is flanked by a series of upstream repressor elements for REST, Freud-1/CC2D1A and Freud-2/CC2D1B factors that not only restrict its expression to neurons, but may also regulate the level of expression of 5-HT1A receptors in various subsets of neurons, including serotonergic neurons. A separate set of allele-specific factors, including Deaf1, Hes1 and Hes5 repress at the HTR1A C(-1019)G (rs6295) polymorphism in serotonergic neurons in culture, as well as in vivo. Pet1, an obligatory enhancer for serotonergic differentiation, has been identified as a potent activator of 5-HT1A autoreceptor expression. Taken together, these results highlight an integrated regulation of 5-HT1A autoreceptors that differs in several aspects from regulation of post-synaptic 5-HT1A receptors, and could be selectively targeted to enhance serotonergic neurotransmission."

http://www.ncbi.nlm.nih.gov/pubmed/21619616 - Note: This might be something, if we break it down..

6. "Our data suggest that an enhanced capacity of HTR1B or HTR1A transcriptional activity may impair desensitization of the autoreceptors during SSRI treatment."

http://www.ncbi.nlm.nih.gov/pubmed/19829169 Note: NO SHIT! These motherfuckers studied this in 2009

7."sociopathy is made based on their specific dysfunctions in emotional processing, behavioral profiles, etiological pathways, HPA-axis functioning, and serotonergic profiles. Next, it is examined how various polymorphisms in serotonergic genes (e.g., TPH, 5HTT, HTR1A, HTR2A, HTR2C, and HTR3) might contribute either individually or interactively to the development of these disorders and through which specific biological and behavioral endophenotypes this effect could be mediated. http://www.ncbi.nlm.nih.gov/pubmed/23644029 -

8. Aerobic and exhaustive exercise transiently changed the expression of 21 and 16 genes, respectively, with the peak at 4 hours. Only 2 genes significantly responded to both types of exercise. Exhaustive but not aerobic exercise produced a secondary response with significantly altered expression of 14 genes at 24 hours. Five of those genesencode receptors for neurotransmitters (HTR1A, CHRNB2, GABRB3, GABRG3, and LOC51289).

http://www.ncbi.nlm.nih.gov/pubmed/17873550 - Note: What is the difference between HTR1A verse 5-HT1A receptor. Exercise works

[Moloch]

Ghost on Fri Dec 12, 2014 3:00 pm

Good Stuff , Cell.

This kind of technology is used in genetically modifying corn and food products, just not on humans yet.

I really think that this is what will eventually be able to cure us. I really do. All the other stuff is just beating around the problem.

1)That is one hell of an article.

"We propose that by understanding the transcriptional regulation of the 5-HT1A receptor it may be possible to regulate its expression differentially in raphe and projection regions. Here we review the transcriptional architecture of the 5-HT1A gene (HTR1A) with a focus on specific DNA elements and transcription factors that have been shown to regulate 5-HT1A receptor expression in the brain.

I think that I'm going to try and email the authors and ask them a few questions regarding their research within the next week. I could run it by someone here who really understands this stuff and has good questions to ask.

This is his bio:

"working in the area of molecular mechanisms of autoreceptor desensitization. Successful therapy of major depression (as well as generalized anxiety, obsessive-compulsive, and other mental disorders) using a variety of antidepressant compounds (e.g., serotonin-specific reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, and 5-HT1A receptor agonists) is associated with a three-week time course before clinical improvement may be observed. Antidepressants appear to act by directly modifying the serotonin (5-HT) system which originates in the raphe nuclei of the brain. Desensitization of inhibitory serotonin-1A (5-HT1A) autoreceptors occurs following chronic (but not acute) antidepressant treatment, and allows for enhanced firing of serotonergic raphe neurons in the presence of antidepressant

The importance of transcriptional and post-transcriptional events in regulating the 5-HT system is being probed using 5-HT1A receptor promoter constructs with the ultimate aim of identifying genetic sequences that may confer susceptibility to mental disorders or responsiveness to anti-depressant treatment."

This is...wow...this hits the nail on the head...You couldn't pay someone to do research more directed at us.

2) Another good read.

3) HTR1A gene coming up again. I think we're onto it. The gene responsible that is.

4) Another good study.

5) This is another good lead of people to maybe email...

6) HTR1A is simply the piece of genetic code that codes the 5HT-1A receptor. According to Sonny...this is all that's messed up. If you could splice in the HTR1A gene from your mother or father or brothers/ sisters, and they haven't taken an SSRI...you're cured I think. Your body would start producing good 5HT-1A auto-receptors, the post-synaptic side would no longer be bombarded with Serotonin because the autoreceptor would realize that you already have enough. Dopamine would rise because it would no longer be inhibited. PSSD would disappear in a day or 2. The receptors are always being replaced and new ones are being made. They are being MADE desensitized, they aren't the same ones you had while on the med. Hope this helps.

This is good, cell. Great research. Especially article 1, that's recent and really hopeful for the gene theory. Thanks for posting this.

[Moloch]

anacleta on Sat Dec 13, 2014 4:47 am

add
Genetic determinants of selective serotonin reuptake inhibitor related sexual dysfunction.
http://www.ncbi.nlm.nih.gov/pubmed/25493571

[Moloch]

forexworld12 on Sat Dec 13, 2014 12:03 pm

Great stuff man !!

I searched on the internet And the only possible way I see where one can change the expression of HTRIA gene is though exhaustive Exercise ...! bad the bad thing is it was not a permanent effect

Aerobic and exhaustive exercise transiently changed the expression of 21 and 16 genes, respectively, with the peak at 4 hours

http://www.ncbi.nlm.nih.gov/pubmed/17873550

[Moloch]

SingleCell on Sat Dec 13, 2014 2:02 pm

forexworld12 wrote:
Great stuff man !!

I searched on the internet And the only possible way I see where one can change the expression of HTRIA gene is though exhaustive Exercise ...!

http://www.ncbi.nlm.nih.gov/pubmed/17873550

Results: Aerobic and exhaustive exercise transiently changed the expression of 21 and 16 genes, respectively, with the peak at 4 hours. Only 2 genes significantly responded to both types of exercise. Exhaustive but not aerobic exercise produced a secondary response with significantly altered expression of 14 genes at 24 hours. Five of those genes encode receptors for neurotransmitters (HTR1A, CHRNB2, GABRB3, GABRG3, and LOC51289).


Has anyone ever tried EXHAUSTIVE EXERCISE?? For like 4 hours a day? everyday? I assume you can alter the expression, but will you do it long enough to heal your desensitized auto-receptor?

[Moloch]

Ghost on Sat Dec 13, 2014 2:28 pm

SingleCell wrote:
forexworld12 wrote:
Great stuff man !!

I searched on the internet And the only possible way I see where one can change the expression of HTRIA gene is though exhaustive Exercise ...!

http://www.ncbi.nlm.nih.gov/pubmed/17873550

Results: Aerobic and exhaustive exercise transiently changed the expression of 21 and 16 genes, respectively, with the peak at 4 hours. Only 2 genes significantly responded to both types of exercise. Exhaustive but not aerobic exercise produced a secondary response with significantly altered expression of 14 genes at 24 hours. Five of those genes encode receptors for neurotransmitters (HTR1A, CHRNB2, GABRB3, GABRG3, and LOC51289).


Has anyone ever tried EXHAUSTIVE EXERCISE?? For like 4 hours a day? everyday? I assume you can alter the expression, but will you do it long enough to heal your desensitized auto-receptor?
It says that the expression has been altered, but it doesn't really specify as to how. My guess is that it would go back if you stopped. I don't know if the SSRI changed the genetic ode itself, or if it just changed how the gene is expressed...


As for turning that gene on and off...Read this. I REALLY am busy today so I only read the first page. It's really dense reading...but it talking about changing the expression of the HTRIA gene...I picked up reading at page 195... Talks about "doxycicline", and if it is absent, the gene won't be transcribed...and therefore 5-HT1A pre-synaptic auto receptors won't be produced in large enough numbers. Wednesday night I'm grabbing a cup of tea and reading that whole chapter...Until then I'm handing it off to you guys to look over. It looks really, really interesting...

https://books.google.com/books?id=Oxj1h ... on&f=false

[Moloch]

r on Sat Dec 13, 2014 2:50 pm

Ghost wrote:
SingleCell wrote:
forexworld12 wrote:
Great stuff man !!

I searched on the internet And the only possible way I see where one can change the expression of HTRIA gene is though exhaustive Exercise ...!

http://www.ncbi.nlm.nih.gov/pubmed/17873550

Results: Aerobic and exhaustive exercise transiently changed the expression of 21 and 16 genes, respectively, with the peak at 4 hours. Only 2 genes significantly responded to both types of exercise. Exhaustive but not aerobic exercise produced a secondary response with significantly altered expression of 14 genes at 24 hours. Five of those genes encode receptors for neurotransmitters (HTR1A, CHRNB2, GABRB3, GABRG3, and LOC51289).


Has anyone ever tried EXHAUSTIVE EXERCISE?? For like 4 hours a day? everyday? I assume you can alter the expression, but will you do it long enough to heal your desensitized auto-receptor?
It says that the expression has been altered, but it doesn't really specify as to how. My guess is that it would go back if you stopped. I don't know if the SSRI changed the genetic ode itself, or if it just changed how the gene is expressed...


As for turning that gene on and off...Read this. I REALLY am busy today so I only read the first page. It's really dense reading...but it talking about changing the expression of the HTRIA gene...I picked up reading at page 195... Talks about "doxycicline", and if it is absent, the gene won't be transcribed...and therefore 5-HT1A pre-synaptic auto receptors won't be produced in large enough numbers. Wednesday night I'm grabbing a cup of tea and reading that whole chapter...Until then I'm handing it off to you guys to look over. It looks really, really interesting...

https://books.google.com/books?id=Oxj1h ... on&f=false

Wait, hold up.

Can you describe in further detail what it says about doxycycline? I, during the summer, did a routine of doxycycline hycate to treat acne and it was around this time that I started improving in earnest. It seems unrelated, as doxycycline is an antibiotic, but regardless I'd like to know more. If i get the time within the next couple days I'll sit down and read that part of the book.

[Moloch]

Ghost on Sat Dec 13, 2014 3:16 pm

r wrote:
Ghost wrote:
SingleCell wrote:
forexworld12 wrote:
Great stuff man !!

I searched on the internet And the only possible way I see where one can change the expression of HTRIA gene is though exhaustive Exercise ...!

http://www.ncbi.nlm.nih.gov/pubmed/17873550

Results: Aerobic and exhaustive exercise transiently changed the expression of 21 and 16 genes, respectively, with the peak at 4 hours. Only 2 genes significantly responded to both types of exercise. Exhaustive but not aerobic exercise produced a secondary response with significantly altered expression of 14 genes at 24 hours. Five of those genes encode receptors for neurotransmitters (HTR1A, CHRNB2, GABRB3, GABRG3, and LOC51289).


Has anyone ever tried EXHAUSTIVE EXERCISE?? For like 4 hours a day? everyday? I assume you can alter the expression, but will you do it long enough to heal your desensitized auto-receptor?
It says that the expression has been altered, but it doesn't really specify as to how. My guess is that it would go back if you stopped. I don't know if the SSRI changed the genetic ode itself, or if it just changed how the gene is expressed...


As for turning that gene on and off...Read this. I REALLY am busy today so I only read the first page. It's really dense reading...but it talking about changing the expression of the HTRIA gene...I picked up reading at page 195... Talks about "doxycicline", and if it is absent, the gene won't be transcribed...and therefore 5-HT1A pre-synaptic auto receptors won't be produced in large enough numbers. Wednesday night I'm grabbing a cup of tea and reading that whole chapter...Until then I'm handing it off to you guys to look over. It looks really, really interesting...

https://books.google.com/books?id=Oxj1h ... on&f=false

Wait, hold up.

Can you describe in further detail what it says about doxycycline? I, during the summer, did a routine of doxycycline hycate to treat acne and it was around this time that I started improving in earnest. It seems unrelated, as doxycycline is an antibiotic, but regardless I'd like to know more. If i get the time within the next couple days I'll sit down and read that part of the book.

Personally, I don't know what it is...but that is REALLY exciting. If I understand what the book is saying, you'd probably have to insert it into your genetic code in the HTRIA gene for the gene to alter 5-HT1A expression...So Idk If just taking it orally would do anything. However, that is a very weird coincidence, and would give further backing to this theory if it could be proven.

How drastic were improvements? Time on acne Medicine? Time off of SSRI's? Time on SSRi? SSRI taken?

If it did help, it would be changing how your body synthesizes 5-HT1A auto receptors, and if it coded more/ some that were more sensitized...you would see PSSD improve in all fronts under the HTRIA gene hypothesis.

[Moloch]

SingleCell on Sat Dec 13, 2014 3:31 pm

Ghost wrote:

How drastic were improvements? Time on acne Medicine? Time off of SSRI's? Time on SSRi? SSRI taken?

If it did help, it would be changing how your body synthesizes 5-HT1A auto receptors, and if it coded more/ some that were more sensitized...you would see PSSD improve in all fronts under the HTRIA gene hypothesis.

You would have to snort the acne antibiotic..

Put it in my blood..

[Moloch]

SingleCell on Sat Dec 13, 2014 3:33 pm

It does look really interesting...

https://books.google.com/books?id=Oxj1hsh4QzcC&pg=PA195&lpg=PA195&dq=HTRIA+expression&source=bl&ots=54QIoPVJ3o&sig=ha3ztNi1-owILopB8cneZH4pL8Y&hl=en&sa=X&ei=B66MVL7HO9D4yQSqsYGgDA&ved=0CDQQ6AEwAw#v=onepage&q=HTRIA%20expression&f=false

Can you get a PDF of the copy Ghost? or anyone?

thx