15 replies to this topic

[tunt01]

Melatonin Precursor Stimulates Growth Factor Circuits in Brain

ScienceDaily (Feb. 5, 2010) — Scientists at Emory University School of Medicine have discovered unexpected properties for a precursor to melatonin, the hormone that regulates sleep cycles.

Melatonin is produced from the neurotransmitter serotonin in a daily rhythm that peaks at night. Melatonin's immediate precursor, N-acetylserotonin, was not previously thought to have effects separate from those of melatonin or serotonin.

Now an Emory team has shown that N-acetylserotonin can stimulate the same circuits in the brain activated by the growth factor BDNF (brain-derived neurotrophic factor).

The results will be published online this week in the Proceedings of the National Academy of Sciences.

The team was led by Keqiang Ye, associate professor of pathology and laboratory medicine, and P. Michael Iuvone, professor of pharmacology and director of research at Emory Eye Center. Researchers from Morehouse School of Medicine and the University of Wisconsin contributed to the paper.

The discovery has implications for the study of how some antidepressants function and may also explain previous observations that N-acetylserotonin has antidepressant activity in animal models of depression.

"Our results suggest that the molecules and pathways involved in mood regulation and circadian rhythms are intertwined," Ye says.

A lack of BDNF, which pushes brain cells to grow and helps them resist stress, is thought to lie behind depression and several neurodegenerative diseases. Ye and his colleagues have been searching for chemicals that can mimic BDNF by activating TrkB, the receptor for BDNF on cells' surfaces.

Several widely prescribed antidepressants (selective serotonin reuptake inhibitors such as fluoxetine/Prozac) increase levels of serotonin in the brain, but the connections between serotonin levels and depression are complex. Because antidepressants seem to take weeks to display their effects, scientists have proposed that their real targets are BDNF and TrkB.

"We were exploring whether the serotonin system is involved in TrkB signaling," Ye says. "We were surprised to find that N-acetylserotonin, but not serotonin or melatonin, can activate TrkB."

N-acetylserotonin could stimulate TrkB even when BDNF was not present, both in cell culture dishes and in mice, Ye and his colleagues found. It could also protect neurons from overstimulation in the same way that BDNF can.

Melatonin is produced at several sites in the body: the pineal gland, the retina and the intestine. One of the most common strains of laboratory mice (C57Bl6) is deficient in making N-acetylserotonin and melatonin and develops retinal degeneration.

The authors observed that in the retinas of mice that produce adequate melatonin, TrkB is turned on at night, a pattern that matches the appearance of N-acetylserotonin. However, the pattern of TrkB activation is flat in C57Bl6 melatonin-deficient mice.

Ye's laboratory is now investigating the mechanism by which N-acetylserotonin activates TrkB. He says that N-acetylserotonin has a short lifetime in the body but similar compounds that are more stable may be useful in treating neurological diseases.

The research was supported by the National Institutes of Health and Research to Prevent Blindness.

[bkaz]

Interesting. Now, if you (I) supplement melatonin, it'll probably suppress endogenous melatonin & N-acetylserotonin production. Would that reduce BDNF production?

[computeTHIS]

Apparently, Acetyl-CoA is responsible for the conversion of serotonin into N-acetylserotonin. See page 4 of: www.charlesgantmd.com/articles/5HTP-as-precursor.pdf

It's my understanding that Acetyl-CoA is responsible for the production of CoQ10. I'm curious though if there's any relation to the production (or under-production) of Acetyl-CoA related to the supplementation of CoQ10. It is also my understanding that ALCAR is converted into Acetyl-CoA and L-carnitine once outside of the mitochondria. This suggests to me that ALCAR would be superior to L-carnitine, however, it has been claimed that the increased hydrogenation of ALCAR in the bloodstream makes it less bioavailable than L-carnitine. Hmmm...

[computeTHIS]

Ah, from the same paper it shows Pantethine (a form of vitamin B5) to be the intermediate responsible for the production of Acetyl-CoA.

[health_nutty]

Thanks for this article. I'm going to stay away from melatonin supplemention because of this.

[X_Danny_X]

@health_nutty

shouldn't you be saying that you will take melatonin supplementation since melatonin or its precursor stimulates brain circuits like BDNF.

[computeTHIS]

Thanks for this article. I'm going to stay away from melatonin supplemention because of this.

@health_nutty

shouldn't you be saying that you will take melatonin supplementation since melatonin or its precursor stimulates brain circuits like BDNF.

I see nothing that would suggest that supplementing melatonin would either stimulate N-acetylserotonin nor suppress it. Melatonin is "the suicidal antioxidant" because once it becomes reduced it no longer functions as an antioxidant. Your body can always use it, and I will continue taking it.

[X_Danny_X]

So melatonin is out of the question. To take advantage of this then we should take ALCAR since it can be used for the production of N-acetylserotonin and Acetyl-CoA which in turn Acetyl-CoA can be used to create CoQ10.

How much of ALCAR can be converted to both? This will be very helpful if ALCAR can be converted in good amounts of N-acetylserotonin and Acetyl-CoA to their job.

[computeTHIS]

So melatonin is out of the question. To take advantage of this then we should take ALCAR since it can be used for the production of N-acetylserotonin and Acetyl-CoA which in turn Acetyl-CoA can be used to create CoQ10.

How much of ALCAR can be converted to both? This will be very helpful if ALCAR can be converted in good amounts of N-acetylserotonin and Acetyl-CoA to their job.

To point out, ALCAR is directly converted into Acetyl-CoA and L-carnitine. Acetyl-CoA is responsible for producing N-acetylserotonin. I have no idea about the amounts.

[computeTHIS]

The bigger question, I think, is if the finding by the OP is the underlying process that all supplements and medicines produce BDNF.

[QuantumTubule]

wow dont you think its worth getting the title of your thread correct?
As the article portrays that Acetylserotonin activates TRKB which is also activated by BDNF. Not that Acetylserotonin activates BDNF.
TRKB is a very important substrate in the brain and plays a very important role is synapes development and vaibility, influences on NMDA subunit activity are important. Increasing TRKB stimulation increase computitional power of neural networks while decreasing apoptic responses. Antidepressent are hypothosised to alleviate depression through increased levels of acetylserotonin usually about a month after begining treatment.
Acetylserotonin has not been approved for interstate commerce as a Nutritional supplement, currently there is no affordable method to source this product. Target daily intakes are in the 4-7mg/kg range. Melatonin is reverse metabolised to Acetylserotonin however only approximatly 10% of this dose undergoes this. Melatonin Supplements certius parbius(and ignoring the reverse metabolism) would decrease acetlyserotonin to a moderate degree.
Acetyl donation from ALCAR to Acetyl-CoA to Acetylserotonin could be a mode of benefit of ALCAR

[X_Danny_X]

Excellent Quantum Tubule, I take ALCAR quite a bit. I wonder if DMAE is inhibiting ALCAR intake. My brain feels heavy since taking ALCAR. I wonder if its because of its sour taste or because being converted to Acetylserotonin in stimulating TRKB???

[computeTHIS]

wow dont you think its worth getting the title of your thread correct?
As the article portrays that Acetylserotonin activates TRKB which is also activated by BDNF. Not that Acetylserotonin activates BDNF.
TRKB is a very important substrate in the brain and plays a very important role is synapes development and vaibility, influences on NMDA subunit activity are important. Increasing TRKB stimulation increase computitional power of neural networks while decreasing apoptic responses. Antidepressent are hypothosised to alleviate depression through increased levels of acetylserotonin usually about a month after begining treatment.
Acetylserotonin has not been approved for interstate commerce as a Nutritional supplement, currently there is no affordable method to source this product. Target daily intakes are in the 4-7mg/kg range. Melatonin is reverse metabolised to Acetylserotonin however only approximatly 10% of this dose undergoes this. Melatonin Supplements certius parbius(and ignoring the reverse metabolism) would decrease acetlyserotonin to a moderate degree.
Acetyl donation from ALCAR to Acetyl-CoA to Acetylserotonin could be a mode of benefit of ALCAR

Thanks for setting us straight. That was a prime example of us not really RTFA. Is all of your information from the original article or do you have another reference for the Acetylserotonin & Melatonin intake data, curiously?

[QuantumTubule]

There is a submission for approval to enter interstate commerce on the FDA website, which is quite an informative start, there are also patents and various studies which are mainly In Vitro, eg PUBMED

10MB;
www.fda.gov/ohrms/dockets/.../95s-0316-rpt0146-01-vol104.pdf

Understanding TRKB will prove alot of work, its an explorative trails from general to specific back many times You will prob need to learn about Glumatic Transmission etc

[tritium]

Melatonin is reverse metabolised to Acetylserotonin however only approximatly 10% of this dose undergoes this. Melatonin Supplements certius parbius(and ignoring the reverse metabolism) would decrease acetlyserotonin to a moderate degree.
Acetyl donation from ALCAR to Acetyl-CoA to Acetylserotonin could be a mode of benefit of ALCAR

So, would it be possible to take a large amount of melatonin such that the reverse metabolism to acetylserotonin would be greater than or equal to the decrease in acetylserotonin production due to supplementation?

Edited by tritium, 20 November 2011 - 07:08 PM.

[QuantumTubule]

No this wouldnt be possable. For instance 50mg Melatonin is considered a very large dose(there are negative effects), this would only produce 5mg of AcetylSerotonin In vivo, this is sufficient for ~1kg of living mass. Therefore Dosages would be in the multigram range per day, which could be lethal as far as I know. As Melatonin has strong effects in the Microgram range, It would be crazy to look at the Gram range.