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Is an Ampakine the missing piece of ciLTP?

ciltep ciltp ampakine noopept ltp

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#1 Lancelott

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Posted 27 November 2015 - 07:07 PM


Hey fellows,

I've been doing some research about chemically induced Long Term Potentiation (CILTEP, ciLTP), and I got really into the subject, cause that seems really promising in my opinion.. And i just started to write an article about it.

 

By this time that i've been reading like every article in the internet that contains any information about this subject, there is a question that just won't let me sleep.. Try to follow my conclusion, and please correct me if i make any mistake.

 

LTP occurs in glutamatergic neurons, after enough stimulation between the same couple of neurons, during a certain period of time and so... OK, we all got it..

The thing is: It only occurs when the NMDA (slow response) receptors are opened, because LTP itself depends on Ca++ entrance into the cell membrane to bind with specific proteins (including the cAMP-depending protein CREB in the late fase), that is only possible by NMDA receptors, which are blocked by Mg++, that will only be released when there's enough potential to cause the electromagnet repulsion of the molecule (that means enough EPSP from the AMPA receptors).

 

Thinking on how LTP depends on NMDA receptors, i was just wondering if an ampakine would help in this stack's synergy.

I was thinking about noopept, since it has good affinity to the NMDAR as well as AMPAR.. I mean, that's the focus isn't it? more (Ca++) + more cAMP (=more CREBS), more LTP right? I mean, thats what the late phase is all about..

Does anybody agree/disagree? any thoughts?

 

I am about to buy forskolin and artichoke, and add this to my usual stack [caffeine 100mg; l-theanine 200mg; l-tyrosine 100mg; ALCAR 500mg; noopept 10mg].. I would take the theanine off because of the anxiolytic effects of CILTEP stacks from reports i read, but it's already capsuled, so whatever.. the only thing is capsuled separately is the ALCAR, but i read something about it helping to avoid the fatigue.. And it also contributes to acetilCoA formation, so, as noopept is also an AChR modulator, i should give it a try..

 

I'll post it once i get it.. but i would really like opinions!

Thanks!


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#2 gamesguru

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Posted 27 November 2015 - 07:51 PM

Exercise and the brain: something to chew on
Henriette van Praag.  2009.

... fisetin was found to improve LTP through a CREB/ERK (cAMP-response-element-binding protein/extracellular signal-regulated kinase) mechanism in acute tissue slices [46]. In vivo, supplementation with a blueberry diet enhanced spatial working memory in rats and increased hippocampal BDNF and CREB levels. Component analysis of the blueberry extract showed that, although the rats consumed more anthocyanins than flavanols, brain and plasma levels of flavanols were the highest. This indicates that flavanols might be directly involved in the observed effects [102]. Furthermore, the combination of fish oil and exercise elevated levels of hippocampal BDNF and its downstream effectors synapsin I and CREB, which are important for learning [13]. Ingestion of cocoa-derived flavanol (−)epicatechin increased expression of hippocampal genes important for synaptic plasticity, such as Notch and Cadherin. A different set of genes was altered with flavanol consumption and wheel running, such as SNAP-25 and Kif17. However, in both sedentary and exercise conditions expression of genes associated with learning was enhanced [12]. The interaction between exercise and natural products, together with evidence for common cellular signaling pathways, indicates that these compounds might have specific neural receptors, analogous to plant products such as opiates and cannabanoids. If such receptors exist it might open new avenues for treatment of neurodegenerative diseases (Figure 1b).

The Cystine/Glutamate Antiporter System xc− in Health and Disease: From Molecular Mechanisms to Novel Therapeutic Opportunities
Jan Lewerenz,corresponding author1 Sandra J. Hewett,2 Ying Huang,3 Maria Lambros,3 Peter W. Gout,4 Peter W. Kalivas,5 Ann Massie,6 Ilse Smolders,7 Axel Methner,8 Mathias Pergande,8 Sylvia B. Smith,9 Vadivel Ganapathy,10 and Pamela Maher11.  2013.

Among the flavonoids tested, the flavonol fisetin, which is found in strawberries, proved to be highly effective. Fisetin not only has antioxidant activity, but is also able to maintain GSH levels. Consistent with this observation, fisetin was shown to increase Nrf2 levels (163).

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Current Evidence of Chinese Herbal Constituents with Effects on NMDA Receptor Blockade
Willmann Liang,* Wai Ping Lam, Hong Chai Tang, Ping Chung Leung, and David T. Yew.  2013.
The research on herbs with NMDA-R effects has provided valuable information on cellular function and intracellular signaling mechanisms. One could extrapolate from these findings and proposes possible clinical applications of the individual herbs. However, in order to better supplement conventional western medicines in targeting the receptor entity, namely the activity of NMDA-R, it is necessary to have greater understanding of molecular interactions between the herbs and the various binding sites on the receptor subunits. Except for a small number of herbs and their constituents, e.g. HupA, GlyA, RRV, much about receptor-binding and -selectivity is yet to be determined. On another note, a majority of the studies reporting the herbal effect on NMDA-R activity used cells related to memory (i.e., from hippocampus) and cognition (i.e., from cortex). The choice of cell types is rational since NMDA-R modulation is strongly correlated with the treatment of AD, but future investigations may also consider examining cells from other brain areas so that potential adverse effects of the target herbs and herbal constituents will not go unnoticed. Lastly, evidence of neuroprotection observed in several herbs may suggest their action on the NMDA-R as well. It will be of interest to study the receptor-binding characteristics of these herbs and their constituents.

Increased glutamate in the hippocampus after galantamine treatment for Alzheimer disease.

Alterations in Hippocampal Oxidative Stress, Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa monnieri Extract.
(-)Epicatechin stimulates ERK-dependent cyclic AMP response element activity and up-regulates GluR2 in cortical neurons.

https://en.wikipedia...nesium_blockade

 

[Expression of AMPA receptors and related protein in immobilization stressed rats and effect of Xiaoyaosan].
[Changes of central AMPA receptor subunits and related protein mRNA expression in immobilization stressed rats and effect of Xiaoyaosan on them].


Edited by gamesguru, 27 November 2015 - 08:03 PM.


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#3 Lancelott

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Posted 27 November 2015 - 08:10 PM

Interesting! I'll look around if i find more stuff about it

 

but i don't really think i got your point.. do you agree, disagree, or none it's just a complementar information?

thanks, i'll do some research on it, brb


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Also tagged with one or more of these keywords: ciltep, ciltp, ampakine, noopept, ltp

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