2626 replies to this topic

[Psionic]

so querceting is dead as it looks like.. If I should go with forskolin, should be better to pick up powder 30g 20% (it means one dose is about ~100mg ?) or capsulated root powder 125mg (10% forskohlin) which contains also some EGCG..
I definitely feel loss in STM with quercetin, can it be worse with long term use? because motivation effects can be felt greatly..

[unbeatableking]

^

Forskolin is supposedly necessary for the stack, it isn't a replacement for Quercetin however.

Forskolin raises cAMP while Quercetin prevents the enzymatic deactivation of cAMP to AMP. They work hand in hand.

The artichoke extract seems to be the only other viable option for Quercetin as of now however.

You want to get a Forskolin supplement with a pure Forskolin concentration below 20 mg. There are a lot of recommendations in this thread.

There is no proof that long-term Quercetin use can lead to permanent working memory issues. The PDE4 inhibition seems to have a reversible MOA.

[abelard lindsay]

Are you saying that the 'theories' I supposedly keep mentioning in this thread are just 'theories'?

Name one 'theory' in this topic which I failed to back up with a study.

That all PDE4 inhibitors causes a decrease in working memory. You made the jump from the cAMP/HCN/Pre-frontal cortex connection to all PDE4 inhibitors impair working memory. The study I referenced multiple times showed that a decrease in cAMP in the PFC caused improved working memory, but a strong PDE4 inhibitor (Rolipram) did not decrease working memory by itself but only interfered with the actions of Guanaficine. This leaves open the possibility that there could be a direct interaction between the PDE4 inhibitor Rolipram and the cAMP decreaser Guanaficine in the brain that is not mediated via cAMP or mediated through some other mechanism.

Now cAMP is regulated by various types of PDE in different parts of the body and in different parts of the brain. For example, PDE5 inhibition has been wildly successful for preventing erectile dysfunction but PDE4 inhibition has no such effect. Even PDE4 has plenty of isoforms among it's four subtypes (PDE4A-D). Some cause nausea, others improve reference memory significantly while others hurt memory performance.

For example:
http://www.ncbi.nlm....pubmed/21209202

Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling.
….
The present results suggest that PDE4D, in particular long-form PDE4D, plays a critical role in the mediation of memory and hippocampal neurogenesis, which are mediated by cAMP/CREB signaling; reduced expression of PDE4D, or at least PDE4D4 and PDE4D5, in the hippocampus enhances memory but appears not to cause emesis. These novel findings will aid in the development of PDE4 subtype- or variant-selective inhibitors for treatment of disorders involving impaired cognition, including Alzheimer's disease.

So PDE4D4 and PDE4D5 inhibition improve memory and neurogenesis.

http://www.ncbi.nlm....pubmed/21458469

Enhanced long-term depression and impaired reversal learning in phosphodiesterase 4B-knockout (PDE4B-/-) mice.
….
On the behavioral level PDE4B(-/-) mice displayed impaired reversal learning in the Morris water maze compared to wild-type littermates, but no differences in acquisition and retention of spatial memory and fear conditioning. Taken together, these results suggest that the PDE4B gene may play a role in synaptic activity and long-term depression and is involved in spatial reversal memory. Our findings support the view that various PDE4isoforms are non-redundant and have distinct neurological roles.

and PDE4B subtypes impair reversal learning.

So what could be going on is that Quercetin is more active at PDE4B subtypes vs PDE4D than artichoke. The confirmed pCREB inhibition of Quercetin doesn't help either.

As we can see, the specificity of PDE4 inhibitors to subtypes and isoforms of PDE4 is still an area of research.

Forskolin also has uneven activity on various PDE4 receptor subtypes when its activity is mediated through Jurkat T-Cells.

http://www.ncbi.nlm..../pubmed/9003416

Challenge of human Jurkat T-cells with the adenylate cyclase activator forskolin elicits major changes in cAMP phosphodiesterase (PDE) expression by up-regulating PDE3 and inducing PDE4D1 and PDE4D2 splice variants as well as down-regulating a novel PDE4A splice variant.
....
Forskolin treatment led to a marked decrease of this novel PDE4A species and allowed the detection of a strong signal for an approximately 67 kDa PDE4D species, suggested to be PDE4D1, but did not induce PDE4B and PDE4C isoforms. Elevation of intracellular cAMP concentrations in Jurkat T-cells thus exerts a highly selective effect on the transcriptional activity of the genes encoding the various PDE4 isoforms. This leads to the down-regulation of a novel PDE4A splice variant and the induction of PDE4D1 and PDE4D2 splice variants, leading to a net increase in the total PDE4 activity of Jurkat T-cells.

So there could be differences between the effects of Sesamin and Forskolin based on how they interact with Jurkat T-cells for example even though they both increase cAMP in aggregate.

Edited by abelard lindsay, 24 August 2012 - 01:15 PM.

[unbeatableking]

^

Would it be fair to presume that Forskolin is unnecessary for this stack?

Good post by the way, upvoted.

Edited by unbeatableking, 24 August 2012 - 01:24 PM.

[nupi]

Considering that both Rhodiola and Quercetin are MAO-BI, is is safe to stack them (OTC Seleginine, maybe?)? After reading up on Forskolin, I dont think I want to play with the stuff (even though I have a bottle of it in the cupboard)

[Daruman]

There are two generalized types of memory, explicit and implicit. Explicit is what we want to focus on with CILTP, and is not effected by sleep. So I believe we can objectively test this, and get some real data.

The experiment would work by having words and numbers shown next to an generated geometric image. The image could be created from a hash function, each being unique. In each experiment we could test between 10-20 matches. A study session would last for 15 min on day 1. Then on the 3 subsequent days a short matching test would be performed, but scores would be hidden. After the last test on the fourth day we could graph the data. This would do this test multiple times for the stack vs placebo, but with new matches each time.

Does this look like it would work to quantify the results? If so, I might be able to program something to do this.

OR Is there a test online that tests long term memory? I couldn't find one.

[gizmobrain]

^

Nefiracetam? You are aware of the testicular side-effects right?

Why'd you switch from Artichoke to Quercetin anyways.

Yes, I've read the studies. I am proceeding with cautious dosages and using it sparingly. If it doesn't work for what I want it to do, then I will drop it immediately. If it does work, I will use it as another point of data in my self-diagnosis, in order to find safer alternatives.

I didn't quite "switch" to Quercetin per se. I have always mixed Artichoke and Quercetin at varying ratios. The main reason I have kept Quercetin around is to combat my seasonal allergies. It is literally the most effective allergy medicine I have ever taken. I can say without a doubt that if my allergies are flared up, my cognitive function and productivity drops far below baseline. A moderate dose of Quercetin (~400mg) taken on high pollen days allows me to breathe.

If we want to find a solution to this issue, then let us.

I just don't understand why some people here are so adamant about defending this stack in an absolute sense. Everything is open to criticism.

Given that the use of Quercetin remained unchallenged for... 10 or more pages perhaps? Only to be proven ill-advised a few pages back by studies and anecdotes, don't you guys think that this criticism has merit?

If no one bothered to bring that issue up, then people might've continued to use it to their detriment.

And forgive me for being so dry and impassive when talking about the stack in question.

I think you'll find that most people aren't adamantly defending this stack, but rather your incessant "attacks" against their posts. You tend to use very strong words, hyperbole, and have an attitude of cockiness that rubs people raw. I think we've all been fairly gentlemanly about it, as (at least speaking for myself) we would rather see you add to the knowledge here instead of making everyone angry and getting told to 'eff' off, "doctor douchebag". Keep digging up information as it relates to the stack, but by all means, try to work on your bedside manner. I couldn't possibly care less, as I'm emotionally distanced from internet land. However, I know how online communities work, and the best progress is made when everyone leaves their egos at the door.

Also, you have to realize that not everyone here has a strong neuroscience background. Everything I know about biology/neuroscience/drugs/pharmaceuticals/nootropics has come from reading this forum and pubmed articles for the past year or so. Sometimes I throw out theories that are wrong. Sometimes I confuse things that I've read. Should I just sit on the sidelines and let the grownups talk?

This is the last I will speak about the social aspect of this discussion. Hopefully we can all work as a team here, and not against each other in some non-existent competition.

As far as Quercetin goes, well, I guess that is my fault. I was going off of empirical data (n=1). It had no basis in scholarly research, only "Hey, I got a sample of Quercetin the other day, and it seemed to be beneficial!" Abelard talked about dropping Quercetin over 10 pages back. He also always recommended not overdoing it on the Forskolin. As you can see, not everyone reads and follows advice.

[sparkk51]

Will guanfacine counteract the positive effects of forskolin and/or artichoke extract? Im taking 3 mg per day.

[gizmobrain]

They definitely will work against each other, however I'm not quite sure what the net result will be.

Guanfacine a selective α2A receptor agonist. It's theorized that it helps the symptoms of ADHD by reducing cAMP signalling in the prefrontal cortex. This stack uses Forskolin to raise cAMP levels, I believe globally (don't quote me on that).

I wonder if Guanfacine co-administered with Forskolin would reverse working memory issues seen by some, while leaving enhanced LTP functioning intact in the other areas of the brain. Maybe this is why it has seen some success as an "add-on" treatment to stimulants.

Edited by zrbarnes, 25 August 2012 - 01:50 AM.

[gizmobrain]

Here is one of the studies I was speaking of back when I was talking about NMDA receptors:

Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP) but did not alter long-term depression (LTD). The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory.

→ source (external link)

Transgenic NR2B Mice had both enhanced prefrontal cortex LTP, and spatial working memory.

One major theory in learning and memory posits that the NR2B gene is a universal genetic factor that acts as rate-limiting molecule in controlling the optimal NMDA receptor's coincidence-detection property and subsequent learning and memory function across multiple animal species. If so, can memory function be enhanced via transgenic overexpression of NR2B in another species other than the previously reported mouse species? To examine these crucial issues, we generated transgenic rats in which NR2B is overexpressed in the cortex and hippocampus and investigated the role of NR2B gene in NMDA receptor-mediated synaptic plasticity and memory functions by combining electrophysiological technique with behavioral measurements. We found that overexpression of the NR2B subunit had no effect on CA1-LTD, but rather resulted in enhanced CA1-LTP and improved memory performances in novel object recognition test, spatial water maze, and delayed-to-nonmatch working memory test. Our slices recordings using NR2A- and NR2B-selective antagonists further demonstrate that the larger LTP in transgenic hippocampal slices was due to contribution from the increased NR2B-containing NMDARs. Therefore, our genetic experiments suggest that NR2B at CA1 synapses is not designated as a rate-limiting factor for the induction of long-term synaptic depression, but rather plays a crucial role in initiating the synaptic potentiation. Moreover, our studies provide strong evidence that the NR2B subunit represents a universal rate-limiting molecule for gating NMDA receptor's optimal coincidence-detection property and for enhancing memory function in adulthood across multiple mammalian species.

→ source (external link)

Transgenic NR2B Rats had enhanced LTP of hippocampus, spatial working memory, and spatial reference memory.

Edited by zrbarnes, 25 August 2012 - 01:46 AM.

[Lufega]

This stack stopped working for me. I triend low/high doses forskolin with quercetin, vitamin C, artichoke...nothing. I can't get the same response anymore. It may have something to do with the autonomic system and low catecholamines. I do remember it worked beautifully when I was taking phentermine at the same time. Any suggestions? I might give the phen another go..

[sparkk51]

They definitely will work against each other, however I'm not quite sure what the net result will be.

Guanfacine a selective α2A receptor agonist. It's theorized that it helps the symptoms of ADHD by reducing cAMP signalling in the prefrontal cortex. This stack uses Forskolin to raise cAMP levels, I believe globally (don't quote me on that).

I wonder if Guanfacine co-administered with Forskolin would reverse working memory issues seen by some, while leaving enhanced LTP functioning intact in the other areas of the brain. Maybe this is why it has seen some success as an "add-on" treatment to stimulants.

I find it a little strange that increasing cAMP increases dopamine production but lowers prefrontal cortex functioning. Isnt dopamine supposed to increase prefrontal cortex functioning?

I do understand that, generally, dopamine and cAMP do not have the same mechanisms of action. I just wish to know if taking guanfacine is detrimental to CILTEP's effects.

Edited by sparkk51, 25 August 2012 - 03:18 AM.

[unbeatableking]

There are two generalized types of memory, explicit and implicit. Explicit is what we want to focus on with CILTP, and is not effected by sleep. So I believe we can objectively test this, and get some real data.

The experiment would work by having words and numbers shown next to an generated geometric image. The image could be created from a hash function, each being unique. In each experiment we could test between 10-20 matches. A study session would last for 15 min on day 1. Then on the 3 subsequent days a short matching test would be performed, but scores would be hidden. After the last test on the fourth day we could graph the data. This would do this test multiple times for the stack vs placebo, but with new matches each time.

Does this look like it would work to quantify the results? If so, I might be able to program something to do this.

OR Is there a test online that tests long term memory? I couldn't find one.

Both explicit (declarative) memory and implicit (procedural) memory are affected by sleep. What differs is when they are consolidated. The consolidation of declarative memory occurs during deep sleep while the consolidation of procedural memory occurs during REM sleep.

I'd be more than willing to subject whatever data you find through SPSS programming.

[medievil]

Thats why, the brain is very complex:)

"The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder
Amy FT Arnsten
Author information ► Copyright and License information ►
The publisher's final edited version of this article is available at Expert Rev Neurother
Go to:
Abstract
Neuropsychiatric disorders involve dysfunction of the prefrontal cortex (PFC), a highly evolved brain region that mediates executive functioning. The dorsolateral PFC is specialized for regulating attention and behavior, while the ventromedial PFC is specialized for regulating emotion. These abilities arise from PFC pyramidal cell networks that excite each other to maintain goals and rules `in mind'. Imaging studies have shown reduced PFC gray matter, weaker PFC connections and altered PFC function in patients with attention-deficit/hyperactivity disorder. Thus, medications that strengthen PFC network connections may be particularly useful for the treatment of attention-deficit/hyperactivity disorder and related disorders. Recent data show that compounds such as guanfacine can enhance PFC function by stimulating postsynaptic α-2A receptors on the dendritic spines of PFC pyramidal cells where networks interconnect. Stimulation of these receptors inhibits cAMP signaling, thus closing potassium channels and strengthening physiological connections. These actions may benefit patients with weak PFC function."
The full text is freely available

[medievil]

As a note, as ive been posting i overdosed on desoxy because i stupidly redosed as it didnt work, after i took preg and dhea my behaver normalised (glut hypoactivity makes me act erratic on stims due to my shizo) but i still felt extremely confused, my brain felt open as ppl report with this stack but it really felt "waay" to open if that makes sense with extreme confusion, i think it was the cilltep stack as benzo's are helping a ton with the confusion and the openness normalises to what it normally feels like.

I cant pinpount things to this stack but have ppl noticed confusion when they overdo it? I felt confused at times lately even without stims also not really remembering what i did the last day etc can it be related? Obviously taking the high dose desoxy caused those issues but i tried it once in a higher dose years ago and it didnt cause any of that.

Desoxy at those doses must have been overkill togheter with the cilltep stack so it made me think that the negatives i experienced are things i could look out for, for not overdoing this stack.

Edited by medievil, 25 August 2012 - 12:10 PM.

[gizmobrain]

This stack stopped working for me. I triend low/high doses forskolin with quercetin, vitamin C, artichoke...nothing. I can't get the same response anymore. It may have something to do with the autonomic system and low catecholamines. I do remember it worked beautifully when I was taking phentermine at the same time. Any suggestions? I might give the phen another go..

Phentermine is a lot like amphetamine (except more preferential to NE). You can read through my experiences to see that I have had a hard time recreating my initial effects without a small dose of adderall added to the stack, which is probably for a similar reason as you.

May I ask why you take Phentermine instead of amphetamine?

[Daruman]

There are two generalized types of memory, explicit and implicit. Explicit is what we want to focus on with CILTP, and is not effected by sleep. So I believe we can objectively test this, and get some real data.

The experiment would work by having words and numbers shown next to an generated geometric image. The image could be created from a hash function, each being unique. In each experiment we could test between 10-20 matches. A study session would last for 15 min on day 1. Then on the 3 subsequent days a short matching test would be performed, but scores would be hidden. After the last test on the fourth day we could graph the data. This would do this test multiple times for the stack vs placebo, but with new matches each time.

Does this look like it would work to quantify the results? If so, I might be able to program something to do this.

OR Is there a test online that tests long term memory? I couldn't find one.

Both explicit (declarative) memory and implicit (procedural) memory are affected by sleep. What differs is when they are consolidated. The consolidation of declarative memory occurs during deep sleep while the consolidation of procedural memory occurs during REM sleep.

I'd be more than willing to subject whatever data you find through SPSS programming.

I have never used SPSS programming. I looked into it some, and it appears to be unable to do what I specified, but the data could later be entered into SPSS... I would use JAVA and have it output results for each person to use. They could then choose to upload results, but I can't host any kind of server (dorm rules).

EDIT:
Sorry, I just woke up. I understand what you mean, you will run the analysis, I collect the data. I will get working on the programming. Maybe I could host a server at the Engineering building, it could be seen as an Electrical Engineering project. XD

Edited by Daruman, 25 August 2012 - 01:55 PM.

[Lufega]

This stack stopped working for me. I triend low/high doses forskolin with quercetin, vitamin C, artichoke...nothing. I can't get the same response anymore. It may have something to do with the autonomic system and low catecholamines. I do remember it worked beautifully when I was taking phentermine at the same time. Any suggestions? I might give the phen another go..

Phentermine is a lot like amphetamine (except more preferential to NE). You can read through my experiences to see that I have had a hard time recreating my initial effects without a small dose of adderall added to the stack, which is probably for a similar reason as you.

May I ask why you take Phentermine instead of amphetamine?

I discovered the synergy by chance. I was taking it for weight loss when I added the ciltep stack. I'm not surprised though since I have dysautonomia so my catecholamines are out of whack.

[Major Legend]

PDE4 inhibition shouldn't impair working memory by itself, there is a good chance that the working memory impairment only happens with people that already have a working memory problem such as myself, slight decrease in working memory is detrimental with me, but might not be for others in those cases benefits of LTP potentiation would outweigh the consequences.

I think people should give this a go, as there are no worrying reported side effects and artichoke and forksolin is easy to obtain you can only benefit from this. (In comparison to other mentioned chemicals on this forum, where people actually have some very disturbing side effects like forgetting where they have been and so on...)

This stack stopped working for me. I triend low/high doses forskolin with quercetin, vitamin C, artichoke...nothing. I can't get the same response anymore. It may have something to do with the autonomic system and low catecholamines. I do remember it worked beautifully when I was taking phentermine at the same time. Any suggestions? I might give the phen another go..

Phentermine is a lot like amphetamine (except more preferential to NE). You can read through my experiences to see that I have had a hard time recreating my initial effects without a small dose of adderall added to the stack, which is probably for a similar reason as you.

May I ask why you take Phentermine instead of amphetamine?

I discovered the synergy by chance. I was taking it for weight loss when I added the ciltep stack. I'm not surprised though since I have dysautonomia so my catecholamines are out of whack.

Have you tried one time high dose caffeine, just to see if its to do with your catecholamines?

[Major Legend]

They definitely will work against each other, however I'm not quite sure what the net result will be.

Guanfacine a selective α2A receptor agonist. It's theorized that it helps the symptoms of ADHD by reducing cAMP signalling in the prefrontal cortex. This stack uses Forskolin to raise cAMP levels, I believe globally (don't quote me on that).

I wonder if Guanfacine co-administered with Forskolin would reverse working memory issues seen by some, while leaving enhanced LTP functioning intact in the other areas of the brain. Maybe this is why it has seen some success as an "add-on" treatment to stimulants.

Guanfacine is also sedative, because the stimulation of those andrenergic receptors also produce a wide parasympathetic effect, this is why guanfacine hasn't been very popular, there is myriad of possible side effects (not as bad as its brother clonidine thought)

[sparkk51]

They definitely will work against each other, however I'm not quite sure what the net result will be.

Guanfacine a selective α2A receptor agonist. It's theorized that it helps the symptoms of ADHD by reducing cAMP signalling in the prefrontal cortex. This stack uses Forskolin to raise cAMP levels, I believe globally (don't quote me on that).

I wonder if Guanfacine co-administered with Forskolin would reverse working memory issues seen by some, while leaving enhanced LTP functioning intact in the other areas of the brain. Maybe this is why it has seen some success as an "add-on" treatment to stimulants.

Guanfacine is also sedative, because the stimulation of those andrenergic receptors also produce a wide parasympathetic effect, this is why guanfacine hasn't been very popular, there is myriad of possible side effects (not as bad as its brother clonidine thought)

I'm pretty sure its the opposite. Guanfacine has a much better side effect profile than Clonidine.

[sparkk51]

Which naturally occuring substances lower cAMP? Perhaps something that increases PDE4?

[gizmobrain]

Which naturally occuring substances lower cAMP? Perhaps something that increases PDE4?

You might be in the wrong thread for that discussion since this thread mostly about exploiting increased cAMP levels in order to increase the likelihood of LTP taking place.

I do remember that some substance that inhibits PDE4 at a high dose, but promotes at a low dose. Can't seem to remember what it is though... maybe one of the ginsengs?

Basically, if you want naturally lower cAMP levels, avoid anything that increases them .

Edited by zrbarnes, 26 August 2012 - 01:32 AM.

[health_nutty]

Why would you want to lower cAMP?

Sent from my SCH-I510 using Tapatalk 2

[gizmobrain]

For anyone interested in a summary of some of the pathways presented in this thread, I found this to be a nice resource:

http://info.med.yale...n/Research.html

It includes discussion of cAMP, PDE4, PFC, Guanfacine, DA, and NE.

Edited by zrbarnes, 26 August 2012 - 04:39 PM.

[gizmobrain]

Transcripts' class='bbc_url' title='External link' rel='nofollow external'>http://www.sciencedirect.com/science/article/pii/S0898656808002258']Transcripts for the PDE4A10 cyclic AMP phosphodiesterase isoform are present in a wide variety of rat tissues including the heart. Sequence comparisons between the putative human and mouse promoters revealed a number of conserved regions including both an Sp1 and a CREB-binding site. The putative mouse PDE4A10 promoter was amplified from genomic DNA and sub-cloned into a luciferase reporter vector for investigation of activity in neonatal cardiac myocytes. Transfection with this construct identified a high level of luciferase expression in neonatal cardiac myocytes. Surprisingly, this activity was down-regulated by elevation of intracellular cAMP through a process involving PKA, but not EPAC, signalling. Such inhibition of the rodent PDE4A10 promoter activity in response to elevated cAMP levels is in contrast to the PDE4 promoters so far described. Site-directed mutagenesis revealed that the Sp1 binding site at promoter position − 348 to − 336 is responsible for the basal constitutive expression of murine PDE4A10. The conserved CREB-binding motif at position − 370 to − 363 also contributes to basal promoter activity but does not in itself confer cAMP inhibition upon the PDE4A10 promoter. EMSA analysis confirmed the authenticity of CREB and Sp1 binding sites. The transcriptional start site was identified to be an adenine residue at position − 55 in the mouse PDE4A10 promoter. We present evidence that this novel down-regulation of PDE4A10 is mediated by the transcription factor ICER in a PKA dependent manner. The pool of cAMP in cardiac myocytes that down-regulates PDE4A10 is regulated by β-adrenoceptor coupled adenylyl cyclase activity and via hydrolysis determined predominantly by the action of PDE4 (cAMP phosphodiesterase-4) and not PDE3 (cAMP phosphodiesterase-3). We suggest that increased cAMP may remodel cAMP-mediated signalling events by not only increasing the expression of specific PDE4 cAMP phosphodiesterases but also by down-regulating specific isoforms, such as is shown here for PDE4A10 in cardiac myocytes.

→ source (external link)

Interesting.

Edited by zrbarnes, 26 August 2012 - 06:44 PM.

[NDM]

Why do they say in that link that cAMP is disinhibited with aging: isn't cAMP supposed to enhance learning? And then what's left of "you can't teach old dogs new tricks" and the general assumptions that younger age means better ability to learn? If cAMP increase diminishes prefrontal function and if great prefrontal function is the hallmark of human intelligence, then what's the point of taking substances that increase cAMP? The more I read into this thread, the higher the confusion.

[gizmobrain]

Why do they say in that link that cAMP is disinhibited with aging: isn't cAMP supposed to enhance learning? And then what's left of "you can't teach old dogs new tricks" and the general assumptions that younger age means better ability to learn? If cAMP increase diminishes prefrontal function and if great prefrontal function is the hallmark of human intelligence, then what's the point of taking substances that increase cAMP? The more I read into this thread, the higher the confusion.

Like most things in the brain, it's all about the u-shaped curve, my friend.

[sparkk51]

Why would you want to lower cAMP?

Sent from my SCH-I510 using Tapatalk 2

Well, according to studies, increased cAMP within the forebrain impairs its functioning. However, what's discussed in this thread is that increased cAMP will promote LTP, so I am unsure as to what I should desire here. Obviously, having too much or too little cAMP should be avoided.

What I'm having trouble understanding is how cAMP impairs functioning within the forebrain even though its role is to facilitate better learning. So, what exactly should I be aiming for here?

Do I want to increase or decrease cAMP in the forebrain (I have ADD)?

Should I desire less cAMP in my forebrain and more in other regions of my brain?

Should I not be tampering with cAMP promoters at all?

Does Guanfacine affect cAMP in other areas of the brain?

[gizmobrain]

Completely forgot about Blueberries. Should be synergistic with this stack:

' class='bbc_url' title='External link' rel='nofollow external'>http://www.ncbi.nlm.nih.gov/pubmed/18457678']
Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels.

Phytochemical-rich foods have been shown to be effective at reversing age-related deficits in memory in both animals and humans. We show that a supplementation with a blueberry diet (2% w/w) for 12 weeks improves the performance of aged animals in spatial working memory tasks. This improvement emerged within 3 weeks and persisted for the remainder of the testing period. Memory performance correlated well with the activation of cAMP-response element-binding protein (CREB) and increases in both pro- and mature levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. Changes in CREB and BDNF in aged and blueberry-supplemented animals were accompanied by increases in the phosphorylation state of extracellular signal-related kinase (ERK1/2), rather than that of calcium calmodulin kinase (CaMKII and CaMKIV) or protein kinase A. Furthermore, age and blueberry supplementation were linked to changes in the activation state of Akt, mTOR, and the levels of Arc/Arg3.1 in the hippocampus, suggesting that pathways involved in de novo protein synthesis may be involved. Although causal relationships cannot be made among supplementation, behavior, and biochemical parameters, the measurement of anthocyanins and flavanols in the brain following blueberry supplementation may indicate that changes in spatial working memory in aged animals are linked to the effects of flavonoids on the ERK-CREB-BDNF pathway.

→ source (external link)

' class='bbc_url' title='External link' rel='nofollow external'>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2850944']
Blueberry Supplementation Improves Memory in Older Adults

The prevalence of dementia is increasing with expansion of the older adult population. In the absence of effective therapy, preventive approaches are essential to address this public health problem. Blueberries contain polyphenolic compounds, most prominently anthocyanins, which have antioxidant and anti-inflammatory effects. In addition, anthocyanins have been associated with increased neuronal signaling in brain centers mediating memory function as well as improved glucose disposal, benefits that would be expected to mitigate neurodegeneration. We investigated the effects of daily consumption of wild blueberry juice in a sample of nine older adults with early memory changes. At 12 weeks, we observed improved paired associate learning (p = 0.009) and word list recall (p = 0.04). In addition, there were trends suggesting reduced depressive symptoms (p = 0.08) and lower glucose levels (p = 0.10). We also compared the memory performances of the blueberry subjects with a demographically-matched sample who consumed a berry placebo beverage in a companion trial of identical design and observed comparable results for paired associate learning. The findings of this preliminary study suggest that moderate-term blueberry supplementation can confer neurocognitive benefit and establish a basis for more comprehensive human trials to study preventive potential and neuronal mechanisms.

→ source (external link)