4 replies to this topic

[Kraser]

Hello,

I've been looking at old posts on this forum as well as Reddit and have came across a topic that is not talked about anymore. Here are the posts that I've been looking at: Reddit, Longecity, Reddit, Reddit.

I know these are on Noopept, but it would apply to other compounds that increase BDNF, such as SEMAX, Tianeptine, etc. In the last post I listed, this study is posted: BDNF down-regulates neurotrophin responsiveness, TrkB protein and TrkB mRNA levels in cultured rat hippocampal neurons. Is this really a problem? A comment on one of the posts says that LM22A-4 can be used (but since that is not really that available) another person said Forskolin can regulate the TrkB receptor: Expression of the neurotrophin receptor trkB is regulated by the cAMP/CREB pathway in neurons

I made a post on r/nootropics but it didn't get much response except user Ballaticianaire commented:

http://www.ncbi.nlm....pubmed/19240853

"Chronic treatment with Noopept was not followed by the development of tolerance, but even potentiated the neurotrophic effect."

• I can't say with absolute certainty, but that's obviously implying that, instead of the known trkb downregulation from chronic BDNF expression, it will actually increase in efficacy. I'm not sure if the potentiation means that, as you take noopept longer, it leads to greater increases in BDNF/neurotrophins.. or increases the effectiveness of the upregulated BDNF signaling (and thus no receptor downregulation obviously). I'd definitely like to know that.

http://www.ncbi.nlm....pubmed/21395007

• "Under conditions of chronic administration (28 days, 0.5 mg/day, i.p.), noopept decreased the activity of stress-induced kinases (SAPK/JNK 46/54 and pERK1/2) in rat hippocampus and increases the level of mRNA of the BDNF gene in both hypothalamus and hippocampus. . . . the activation of stress-induced kinases, as an important factor of amyloidogenesis and tau-protein deposition in brain tissue, and the role of deficiency of the neurotrophic factors in the development of neurodegenerative processes. . . . noopept administration suggest that this drug has as pecific activity with respect to some pathogenetic mechanisms involved in the Alzheimer disease."

• So, through BDNF increased via noopept, it's not exactly clear whether that robust Trkb downregulation occurs.. still equivocal/uncertain at this point. However, even with noopept administration, there IS a downregulation of ERK.. so this definitely gives somewhat good reason to think, that the typical Trkb downregulation may indeed occur. However, the last quote there implies noopept may be an efficacious treatment for Alzheimer's disease, which implies there either was no downregulation of Trkb/reduced BDNF response, or they simply didn't test for it.

http://www.intechope...odulation-of-bd

• Apropos the ERK pathway downregulation however - "Ultimately, Erk1/2 signaling not only promotes local axonal growth via cytosolic signaling events, but activated Erk1/2 can also translocate to the nucleus to phosphorylate and activate transcription factors, such as CREB (cAMP response element-binding), leading to the initiation of transcriptional events and the expression of immediate early genes (IEGs), which can further modulate the response".

• So, clearly the ERK pathway is one of the main pathways mediated by BDNF signaling. However, it's also known that ERK signaling will promote differentiation.. downregulation of it can promote cell proliferation. The implication here is an increased neural stem cell pool. Perhaps intermittent cycles of chronic noopept use (or more profound BDNF inducing drugs/analogs), and drugs that promote neurogenesis used in cycle, could promote some major neurogenesis. Conversely, however, using forskolin, or another robust cAMP stimulator, could possibly produce both results concomitantly - it does appear the Trkb receptor expression itself is upregulated/controlled via downstream signaling via CREB and such.

• Actually, as I had nothing else to say here and decided to search for a study on this topic, more specific and pertinent, and found this: http://openworks.woo...dentstudy/6232/ --- "Qualitative Real-Time PCR evaluation of the TrkB full-length receptor and isoforms from hippocampal tissue revealed significant down-regulation of the TrkB full-length receptor between the control and high dosage groups." From noopept administration. Well, this might be the nail in the coffin then. We need the full text!

 

I was just curious as everyone always talks about how great BDNF is but I never see this mentioned at all.
 

Can anyone help expand this? Thanks for any help.

[RPD]

Until I can visualize the mechanical processes and know the relative masses and leverages on each point of action relative to the others I cannot rationally form a model with much predictive power - I cannot rationally know what is significant to my life processes and what is not.

But that does not mean I have to be clueless because of my ignorance.  I general consume recommended but essentially unknown substances by carefully mouthing them in VERY small amounts.   I give my senses the time and priority it takes for them to do a chemical assay with a reckoning of significance  -  There is more of me that is like a blood hound than is not - and that now useful part is only available if I cut the internal chatter and figuratively give that part the  'speaker's staff'.

It is a good thing to avoid foolish risks and trouble.

Edited by RPD, 15 June 2014 - 12:38 PM.

[RPD]

"The implication here is an increased neural stem cell pool."
From a mechanical point of view:

Increases in a system's buffering points and their capacity increases both effective strength and durability.  

IMHO, Increases in a systems inertial energy may increase effective strength but will likely do so at a loss of control responsiveness and system durability - operator skill and command autonomy become much more significant. 
IMHO, Unbalanced increases in a system's inertial energy will likely increase its mechanical effectiveness but at the increased risk of catastrophic failure. 

Edited by RPD, 15 June 2014 - 01:10 PM.

[Makarov]

While you figure everything out, I'd say the best bet to take is to cycle Noopept and add EPA + Forskolin to your stack.

[Kraser]

I stopped taking noopept for now as I don't really have a reason to need it atm but I plan to try it again this fall but hopefully by then I'll have a little more information about this. Does anyone else have any knowledge on this subject?