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GABAergic inhibition of neurogenesis in adult brain


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#1 nidhogg

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Posted 13 October 2012 - 03:22 PM


I just finished reading two papers showing evidence that GABAergic activity inhibits progenitor cell neuroblast and migration. Progenitor cells, for those who dont know, are newborn neural cells that undergo a differentation process into mature neurons. They are the first step into neurogenesis, induced by BDNF and other mechanisms which people here are trying to achieve. But on the other hand, GABAergic activity seems to increase proliferation. This has something to do with progenitor cell depolarization(excitation) but ionotropic receptors is not my strong side, so maybe someone can shed some light into it.

The opposite function is driven by glutamate receptor activity (AMPA & NMDA) which promotes migration and differentation. So heres a crazy idea, instead of juicing up on AMPAkines and trying to increase BDNF in any means which seems to be bottle-necked by GABA anyway, why not inhibit GABAergic activity to some degree? The thought does indeed scream "DANGER" considering convulsions, but there is a right way and a wrong way to do everything.

Ofc, long term this would result in GABAergic upregulation due to direct receptor interaction. Perhaps an indirect downregulator would be better.
L-theanine does not look so good now. That it might boost BDNF to a certain degree could directly be regarded as a homeostasis compensation from neurogenesis inhibition. For neuroprotection, sure, but if you want the best out of neurogenesis then no.

Also, to anyone suffering from excitatory medical conditions(epilepsy, anxiety, insomnia etc), stay away please.

Some things to consider:
Pregnenolone, GABA antagonist, increase neurogenesis.
Chronic, but not short term, administration of Eszopiclone(GABA agonist) induces neurogenesis. If above hypothesis is true this could be explained by overall GABAergic activity downregulation by chronic excessive activity.
Bicuculline, GABA A antagonist, increase speed of neuroblast migration by 27%
Benzodiazepines and alcohol, inhibitory effect on neurogenesis

Note that neurogenesis does not equal BDNF increase, this is "one step further" into the mechanism.


Papers:
http://www.ncbi.nlm....cles/PMC2556597
http://www.academia....nerated_neurons
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#2 OpenStrife

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Posted 13 October 2012 - 03:53 PM

Inhibiting GABA decreases abilities to focus and block out unwanted thoughts.

Gaba is a strange chemical. It's very nature suggest that it would be counter productive to things such as studying and learning.

Though, if you take things like L-Theanine, a GABA precursor, you will notice a marked increase in learning ability, ability to focus, and ability to block out undesired stimuli.

Point being, GABA has a multi-functional role in the brain.


Increased GABA activity = more concentration, more relaxation, more focus. Studies show hat experienced meditators who spend their time cultivating their concentration abilities have higher levels of GABA than the normal person.



If increasing GABA has the effect of increasing concentration, relaxation, and learning, then decreasing it's activity must have the opposite.

This can also be seen in the case of benzo- users. Benzos mess with the GABA system, and on the come down and for a while after GABA levels are significantly decreased.

If you've ever used Benzos you would know what this feels like. Your focus is decreased, you're easily agitated, learning is more difficult, etc.

While GABA inhibits those cellular functions that you describe, it is likely not a bad thing. It is likely doing it for a beneficial reason. I have years of experience with GABAergic supplements and drugs and I am very familiar with the effects of increased and decreased GABA levels.

Edited by OpenStrife, 13 October 2012 - 03:54 PM.

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#3 nidhogg

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Posted 13 October 2012 - 05:46 PM

You are right, GABA is regulating focus and does help learning. But learning does not equal neurogenesis. LTP can also be achieved by change in neuroplasticity by rearranging neurons.
But for generating new neurons for more "brain power" it would appear counter productive.

As far as benzos goes, i'd think the decreased GABAergic activity is related to desensitization and not by lower GABA levels. In fact it should result in increased GABA neurotransmitter levels. And the thing its, its fairly known that substances may accumulate in certain parts in the brain more than others which results in more desentisization there than elsewhere.

But i think your statements are over exaggerated. Im not talking about completely eliminating GABAergic activity, but reducing it. Considering receptor binding follows first order kinetics a slight reduction would result in a fair boost. Ofc one would have to know the corresponding affinities for those proteins before making such a conclusion.

Also, the positive effects of GABA may not even be related to the same receptor subtype.

#4 Galaxyshock

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Posted 14 October 2012 - 08:12 AM

Don't mess with the GABAergic system
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#5 OpenStrife

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Posted 14 October 2012 - 12:51 PM

Don't mess with the GABAergic system


If that was advice I took in high school I would have completely failed. I owe my success in high-school to using L-Theanine to boost my levels of GABA so I could focus and learn. It enabled me to get the highest grade in my Pre-Calculus class the second time I took it, when I originally failed the class the first time with a 29. The L-Theanine boosting my GABA allowed me to focus to such a degree that I got a perfect score(103) plus some the second time around. It allowed me to concentrate and utilize my willpower to actually get work done.

Natural GABA substances are wonderful with proper use.

Edited by OpenStrife, 14 October 2012 - 12:52 PM.

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#6 Galaxyshock

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Posted 14 October 2012 - 04:36 PM

Theanine isn't really messing with the system. I meant taking drugs that do major changes in the most imporant inhibtory neurotransmission system. GABA-antagonists can be neurotoxic and induce seizures.

#7 OpenStrife

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Posted 14 October 2012 - 04:50 PM

Theanine isn't really messing with the system. I meant taking drugs that do major changes in the most imporant inhibtory neurotransmission system. GABA-antagonists can be neurotoxic and induce seizures.



In terms of substances that mess with the GABA systems....there are 2 types. (sorry if this is the same thing you are saying. If it is, then consider this an expansion of your point)

You have substances such as Theanine, which are natural to the brain. The brain knows how to handle it and it doesn't really get in the way or drastically affect any normal process. Yet it will prove to be beneficial when you attempt a task that naturally requires GABA - such as concentration.

Then you have substances such as Xanax, Valium, etc. These are not natural to the brain. The brain does not know how to handle or control them. As a result they float about in the brain/bloodstream interacting with the GABA receptors that they come across. Having potentially unpredictable or uncontrollable effects.

The only way the body handles the latter is through elimination of it through the liver or by some similar mechanism. But with substances such as theanine, that the brain knows how to handle, it can mediate it's workings and turn it on and off when it is needed, controlling it's activity in the system, unlike with the latter.

Put simply, GABAergic substances that are not natural to the body or that the body does not know how to naturally handle are likely to have a negative impact on the GABAergic system. Natural substances can have the opposite effect, an aiding effect.

Edited by OpenStrife, 14 October 2012 - 04:50 PM.


#8 Dissolvedissolve

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Posted 14 October 2012 - 05:35 PM

Theanine isn't really messing with the system. I meant taking drugs that do major changes in the most imporant inhibtory neurotransmission system. GABA-antagonists can be neurotoxic and induce seizures.



In terms of substances that mess with the GABA systems....there are 2 types. (sorry if this is the same thing you are saying. If it is, then consider this an expansion of your point)

You have substances such as Theanine, which are natural to the brain. The brain knows how to handle it and it doesn't really get in the way or drastically affect any normal process. Yet it will prove to be beneficial when you attempt a task that naturally requires GABA - such as concentration.

Then you have substances such as Xanax, Valium, etc. These are not natural to the brain. The brain does not know how to handle or control them. As a result they float about in the brain/bloodstream interacting with the GABA receptors that they come across. Having potentially unpredictable or uncontrollable effects.

The only way the body handles the latter is through elimination of it through the liver or by some similar mechanism. But with substances such as theanine, that the brain knows how to handle, it can mediate it's workings and turn it on and off when it is needed, controlling it's activity in the system, unlike with the latter.

Put simply, GABAergic substances that are not natural to the body or that the body does not know how to naturally handle are likely to have a negative impact on the GABAergic system. Natural substances can have the opposite effect, an aiding effect.


I would just like to clarify that both benzos and theanine have relatively similar modes of action. Benzos are positive allosteric modulators of the GABA-A site, whereas theanine has primarily GABA releasing effects (along with a whole host of other effects). I suspect the difference in tolerance withdrawal between these two substances is due to differing modes of action as well as the fact that theanine is nowhere near as potent as benzos are.

Discussion of substances being "natural to the brain" is a bit absurd. It's not as if humans co-evolved with theanine or something along those lines. There are plenty of natural toxins and plenty of unnatural nootropics.
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#9 OpenStrife

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Posted 14 October 2012 - 06:58 PM

I would just like to clarify that both benzos and theanine have relatively similar modes of action. Benzos are positive allosteric modulators of the GABA-A site, whereas theanine has primarily GABA releasing effects (along with a whole host of other effects). I suspect the difference in tolerance withdrawal between these two substances is due to differing modes of action as well as the fact that theanine is nowhere near as potent as benzos are.

Discussion of substances being "natural to the brain" is a bit absurd. It's not as if humans co-evolved with theanine or something along those lines. There are plenty of natural toxins and plenty of unnatural nootropics.



Theanine is NATURAL. It is a natural pre-cursor in the GABA synthesis cycle.


You are right that they have similar modes of action, but they do not have the same effects.

Chemical reactions in the brain REGULATE the use of GABA. You can have all the GABA in the world in your brain but if your brain is not doing some sort of action that requires it then it will not be put to use.

Though with things such as Xanax, the body cannot regulate the activity of these molecules. These molecules float around in the brain reacting directly with the receptors.

While natural GABA is only accepted when it is demanded via chemical reaction.


There is a big difference and it's the primary reason why Xanax can make you practically feel drunk while having directly boosted levels of GABA wont. The GABA can be controlled by the brain. The Xanax can't, the Xanax or other benzo will just run its course until the body can get rid of it.

#10 Dissolvedissolve

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Posted 14 October 2012 - 07:08 PM

My understanding is that GABA is a releasing agent rather than a precursor, but your point is reasonable since your body is only able to release a certain amount of GABA at once. I believe excessive GABA release should not risk neurotoxicity since GABA is primarily inhibitory, but I cannot say with certainty. Just keep in mind that releasing agents are not necessarily safe as some compounds with associated neurotoxicity (MDMA, Amphetamine) have releasing agent activity. I'm obviously not saying theanine is neurotoxic - it's safe and perhaps neuroprotective.

My main point is that I think it's important to avoid using the terminology of "natural" and "unnatural" since these terms are arbitrary. Saying that theanine's pharmacology tends to make it safe is, of course, acceptable.
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#11 OpenStrife

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Posted 14 October 2012 - 09:51 PM

My understanding is that GABA is a releasing agent rather than a precursor, but your point is reasonable since your body is only able to release a certain amount of GABA at once. I believe excessive GABA release should not risk neurotoxicity since GABA is primarily inhibitory, but I cannot say with certainty. Just keep in mind that releasing agents are not necessarily safe as some compounds with associated neurotoxicity (MDMA, Amphetamine) have releasing agent activity. I'm obviously not saying theanine is neurotoxic - it's safe and perhaps neuroprotective.

My main point is that I think it's important to avoid using the terminology of "natural" and "unnatural" since these terms are arbitrary. Saying that theanine's pharmacology tends to make it safe is, of course, acceptable.


Google's Definition of Natural: Existing in or caused by nature; not made or caused by humankind.

GABA is not a precursor, it is an end product. It is an essential Neurotransmitter that humans cannot live without. Meaning it must be able to be created in the body with a very basic and non-specialized food intake - such as basic proteins occurring in nature. Without basic proteins human life is impossible.

With this said, Theanine is part of the natural synthesis of GABA. Theanine occurs in every single human no matter what, if it didn't, that person would have no GABA, and essentially would have no life - they would be dead.

Given these facts it is safe to say that Theanine is Natural & Naturally occuring and the body has the proper equipment(regulatory enzymes) to handle and process it.

Though at this point this is just an argument of basic labeling terminology. Whether or not it's considered natural or not is irrelevant. The fact is the body has mechanisms to handle Theanine.

You won't get brain damage off having too much Theanine as it is mostly inert until it is converted into GABA. Which the Regulatory enzymes will prevent too much GABA from being produced. On the other hand, things like Xanax and Valium do not have such regulatory methods and can cause severe brain damage and even death in very extreme of doses.

Edited by OpenStrife, 14 October 2012 - 09:52 PM.

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#12 golden1

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Posted 14 October 2012 - 10:22 PM

http://en.wikipedia....e_decarboxylase
Theanine isn't really part of the natrual synthesis of GABA as far as I've ever read..glutamate is.

Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is an enzyme that catalyzes the decarboxylation of glutamate to GABA and CO2. GAD uses PLP as a cofactor.


Regardless, the topic was about GABA ANTAGONISM, not AGONISM. So this is all kind of off topic.

#13 protoject

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Posted 14 October 2012 - 10:37 PM

With this said, Theanine is part of the natural synthesis of GABA. Theanine occurs in every single human no matter what, if it didn't, that person would have no GABA, and essentially would have no life - they would be dead.


dude WTF are you talking about.. Theanine is not like Tyrosine or Tryptophan, it is not an endogenously occuring chemical. Also, you are saying that your benefits from theanine are gaba-ergic, but you have no idea if this is actually true because theanine has more than one action in your brain. I won't deny that it could be the gaba-ergic properties it has that are helping you, but it may be something else entirely or combined with that property that you are getting your desired effects from.

#14 OpenStrife

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Posted 14 October 2012 - 10:56 PM

dude WTF are you talking about.. Theanine is not like Tyrosine or Tryptophan, it is not an endogenously occuring chemical. Also, you are saying that your benefits from theanine are gaba-ergic, but you have no idea if this is actually true because theanine has more than one action in your brain. I won't deny that it could be the gaba-ergic properties it has that are helping you, but it may be something else entirely or combined with that property that you are getting your desired effects from.


Theanine is converted into GABA, but taking Theanine brings other benefits such as hightened Dopamine levels which can also aid in concentration. Though, the increase in Dopamine levels is not directly caused by the Theanine, but rather by the boosted levels of GABA which play a role in the regulation of Dopamine production.

As you said, it has more than one action in the brain, more or less - though all of these actions happen as a result of increased GABA levels.

GABA does more in the brain than simply inhibiting undesired thoughts as stated above.

http://en.wikipedia....e_decarboxylase
Theanine isn't really part of the natrual synthesis of GABA as far as I've ever read..glutamate is.

Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is an enzyme that catalyzes the decarboxylation of glutamate to GABA and CO2. GAD uses PLP as a cofactor.


Regardless, the topic was about GABA ANTAGONISM, not AGONISM. So this is all kind of off topic.


Theanine is a Glutamate/Glatamic Acid Analog. While it is not the exact same it functions in a similar manner. The body produces both of these through different chemical pathways depending on the starting substances. The body has more than 1 chemical pathway to use when it comes to producing GABA. If it relied on a single pathway, some people would be certainly screwed if the right foods are not available.

I wouldn't say it is off topic. The OP is suggesting that Antagonist of the GABAergic systems can increase Neurogenesis. Isn't the whole obsession about Neurogenesis revolving around increasing ability to learn, remember, and grow mood states? The point I was making is that Theanine increases GABA levels, which inturn increases ability to learn, remember, and stabilize mood states - all the desired charicteristics of Neurogenesis, at least around the idea of strengthening the mind. What I was discussing is entirely on point.
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#15 Dissolvedissolve

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Posted 15 October 2012 - 12:03 AM

It is not correct to say theanine "is converted into GABA." Rather, it triggers release of GABA in the brain. Here's a description of GABA synthesis, taken from http://www.acnp.org/...008/default.htm

GABA is formed in vivo via a metabolic pathway called the GABA shunt. The initial step in this pathway utilizes a-ketoglutarate formed from glucose metabolism via the Krebs cycle. a-Ketoglutarate is then transaminated by a-oxoglutarate transaminase (GABA-T) to form glutamate, the immediate precursor of GABA. Finally, glutamate is decarboxylated to form GABA by the enzyme(s) glutamic acid decarboxylase (GAD) (18, 39). GAD is expressed only in GABAergic neurons and in certain peripheral tissues which are also known to synthesize GABA (see below).


Edited by Dissolvedissolve, 15 October 2012 - 12:03 AM.


#16 OpenStrife

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Posted 15 October 2012 - 01:43 AM

It is not correct to say theanine "is converted into GABA." Rather, it triggers release of GABA in the brain. Here's a description of GABA synthesis, taken from http://www.acnp.org/...008/default.htm

GABA is formed in vivo via a metabolic pathway called the GABA shunt. The initial step in this pathway utilizes a-ketoglutarate formed from glucose metabolism via the Krebs cycle. a-Ketoglutarate is then transaminated by a-oxoglutarate transaminase (GABA-T) to form glutamate, the immediate precursor of GABA. Finally, glutamate is decarboxylated to form GABA by the enzyme(s) glutamic acid decarboxylase (GAD) (18, 39). GAD is expressed only in GABAergic neurons and in certain peripheral tissues which are also known to synthesize GABA (see below).



Actually it IS correct. Theanine, being a Glutamate analog, is converted into Glutamate which is then converted into GABA....therefor Theanine is converted into GABA by first conversion into Glutamate


http://www.ncbi.nlm....pubmed/16140449

Furthermore, the generation of glutamate increased by reaction of theanine and gamma-glutamyltranspeptidase (gamma-GTP), showed that gamma-GTP converted theanine to glutamate


Edited by OpenStrife, 15 October 2012 - 01:44 AM.

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#17 Dissolvedissolve

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Posted 15 October 2012 - 01:48 AM

http://www.ncbi.nlm....pubmed/16140449

Furthermore, the generation of glutamate increased by reaction of theanine and gamma-glutamyltranspeptidase (gamma-GTP), showed that gamma-GTP converted theanine to glutamate


As far as I can tell, that's referring to the conversion of theanine to glutamate, which should not be surprising given that theanine is a glutamic acid analog. I do not see any reference to theanine being converted to GABA. In any case, this subtopic should probably be concluded since it's pretty off-topic and we aren't making very much progress.

edit: Since GABA can be derived from Glu, you could say theanine could increase GABA through that synthetic pathway (theanine -> Glu -> GABA). This makes no sense in the real world, however, since Glu is an excitatory neurotransmitter, and people are obviously not recommending Glu supplementation for typical GABA effects (sedation/anxiolysis/sleep).

Edited by Dissolvedissolve, 15 October 2012 - 01:54 AM.

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#18 Kompota

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Posted 15 October 2012 - 08:43 AM

....


I believe you might actually have a point, though at the first glance for most people it may seem strange to inhibit GABA, since it would make us feel worse. However, when we talk about GABA and GABA receptors, we forget one important thing: it is a whole complex of different subunits, where each one has a different function and different effect when modulated. The anxiolityc or sedative effects might be desired, but it appears there are also subunits, which are best left untouched or even antagonised / inversely agonised. And exactly that is the problem with most GABA-ergic drugs and compounds (benzos, z-drugs, Phenibut, Valerian, etc.) - they hit all GABA receptor subunits (to a different extend though), and in reality you wouldn't want to do that. I am dealing with protracted withdrawal from benzodiazepines (short-term use) and the only troublesome symptoms left are cognitive deficits. Studies have found out, those are most likely related to the downregulation (due to an agonist use) of a particular subunit. There are trials with compounds, which act as antagonist / inverse agonist at that subunit, but have almost no affinity at the rest of the GABA receptor complex. The results show a certain nootropic activity, even in healthy subjects.

The question would be: are those improvements in cognition due to the immediate pharmacokinetics of those compounds, or could be there some long-term effect with an increase of BDNF perhaps ?

Edited by Kompota, 15 October 2012 - 08:44 AM.


#19 hippocampus

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Posted 15 October 2012 - 07:41 PM

Theanine it's not good for the brain because it's natural, but because it works the way it does. If some unnatural substance would work similar it would be equally good. And benzos aren't harmful because they are unnatural. If there would be some plant that would produce benzo-like substances it would be equally bad. Morphine is also natural and so is atropine or some toxins or whatever. Just because it's natural it doesn't mean it's good (and the other way round).

Anyway, there are some GABA antagonists that work opposite of benzos - they are good for memory and for wakefulness but they are also anxiogenic.

#20 Picard

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Posted 17 December 2012 - 02:24 AM

It's a shame we had to ruin this perfectly good discussion.

#21 dear mrclock

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Posted 17 December 2012 - 03:36 AM

i enjoyed reading the theanine and GABA discussion. the original topic was kind of stupid. wish you guys continue discussing theanine instead...
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#22 kevinseven11

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Posted 17 December 2012 - 01:15 PM

Id agree that gaba inhibition is very beneficial. Gaba Inhibitors upregulate BDNF
http://www.nature.co...pp2011189a.html

#23 michaelh

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Posted 17 January 2013 - 07:03 PM

So theanine doesn't inhibit neurogenesis?
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#24 michaelh

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Posted 20 January 2013 - 12:36 PM

So does theanine inhibit neurogenesis? I consume theanine via drinking tea. Should I stop drinking tea? It seems theanine definitely affects GABA.

Theanine increases alpha waves, this indicates an effect on GABA.

Edited by michaelh, 20 January 2013 - 12:37 PM.


#25 kevinseven11

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Posted 20 January 2013 - 07:08 PM

Theanine inhibits AMPA receptors. This could be the cause, but i am un sure right now.
This study says gaba blockers are nootropic. http://jpronline.inf...ewArticle/11285

Edited by kevinseven11, 20 January 2013 - 07:08 PM.

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#26 michaelh

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Posted 21 January 2013 - 10:08 AM

I just want to know if theanine is a strong enough GABA agonist to inhibit neurogenesis.

If strong GABA agonists cause GABA downregulation, which prevents neurogenesis inhibition, what about mild GABA agonists, like theanine?

I consume theanine via drinking tea.

Edited by michaelh, 21 January 2013 - 10:09 AM.


#27 michaelh

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Posted 25 January 2013 - 08:07 PM

bump...
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#28 michaelh

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Posted 30 January 2013 - 07:30 PM

If strong GABA agonists cause GABA downregulation, which prevents neurogenesis inhibition, what about mild GABA agonists like theanine?

Do Gaba agonists cause gaba downregulation, preventing neurogenesis inhibition? If so, this doesn't sound good. Unless the downregulation just restores GABA to steady, normal levels.

Edited by michaelh, 30 January 2013 - 07:31 PM.


#29 IanMW

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Posted 06 February 2013 - 11:24 PM

Then you have substances such as Xanax, Valium, etc. These are not natural to the brain. The brain does not know how to handle or control them. As a result they float about in the brain/bloodstream interacting with the GABA receptors that they come across. Having potentially unpredictable or uncontrollable effects.


No, this is incorrect. Benzodiazepine receptors in the brain require benzodiazepines to activate them. There are no processes within the brain or body capable of producing them. It has been known since at least the 1980s that plants make benzodiazepine compounds, and that it is also found in animal flesh and organs. Diazepam (Valium) and its metabolites seem particularly prevalent in plants. My guess is that that benzodiazepines are a plant poison to which animal life, Homo sapiens included, have become so adapted to that we can no longer function without them. Unfortunately, linking restrictions prevent me from linking some studies showing this, but search Pubmed for:

Kavvadias D, Abou-Mandour AA, Czygan FC, et al (2000)
Identification of benzodiazepines in Artemisia dracunculus and Solanum tuberosum rationalizing their endogenous formation in plant tissue.
Biochem Biophys Res Commun Mar 5;269(1):290-5


Sand P, Kavvadias D, Feineis D, et al. (2000)
"Naturally occurring benzodiazepines: current status of research and clinical implications."
Eur Arch Psychiatry Clin Neurosci vol 250(4):p 194-202


Kotz U, (1991)
Occurrence of "natural" benzodiazepines.
Life Sci;48(3):209-15


Unseld E, Krishna DR, Fischer C, et al (1989)
Detection of desmethyldiazepam and diazepam in brain of different species and plants.
Biochem Pharmacol Aug 1;38(15):2473-8


Wildman J, Ranalder U. (1988)
Presence of lorazepam in the blood plasma of drug free rats.
Life Sci. 43(15):1257-60.

Wildmann J, Vetter W, Ranalder UB, et al. (1988)
Occurrence of pharmacologically active benzodiazepines in trace amounts in wheat and potato.
Biochem Pharmacol. Oct 1;37(19):3549-59.

While the quantities we get from food are small, they are not insignificant. Benzodiazepine levels can reach pharmaceutical levels in patients with some liver diseases:

Baraldi M, Avallone R, Corsi L, et al (2000)
Endogenous benzodiazepines.
Therapie Jan-Feb;55(1):143-6
So much that medical intervention is necessary:

Zeneroli ML, Venturini I, Stefanelli S, et al, (1997)
Antibacterial activity of rifaximin reduces the levels of benzodiazepine-like compounds in patients with liver cirrhosis.
Pharmacol Res , Jun;35(6):557-60


As for theanine increasing concentration by increasing brain GABA levels, this is almost certainly not what caused the greater alertness. For a start, no normally function brain canm be short of GABA. It is produced in great quantities as part of the Krebs, aka citric acid cycle which provides the main energy source of brains. There is in fact so much that the blood-brain-barrier contains billions of tiny molecular pumps to remove it into the bloodstream for elimination:

Kakee A, Takanaga H, Terasaki T, et al (2001)
Efflux of a suppressive neurotransmitter, GABA, across the blood-brain barrier.
J Neurochem. 2001 Oct;79(1):110-8.

The other problem with the theanine concept is that GABA is usually, thought not always, an inhibitory neurotransmitter which slows neuron 'firing,' so is more likely to inhibit concentration than enhance it.

Ian

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#30 michaelh

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Posted 18 March 2013 - 04:01 PM

Do Gaba agonists cause gaba down-regulation, preventing neurogenesis inhibition? What about mild GABA agonists like theanine?

Is the down-regulation of GABA a bad thing? I just want steady, normal levels.

I take quite a few supplements that increase GABA. These are Bacopa Monnieri, caffeine, theanine and Beta-Alanine

One thing that confuses me. Sleep is incredibly GABAergic, yet it doesn't prevent neurogenesis. This might be because the neurogenesis from sleep is due to lack of sleep raising glucocorticoids, rather then sleep being GABAergic. So further GABA increases could still inhibit neurogenesis.


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