• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

Repair\restore GABA interneurons

interneurons repair gaba hdac

  • Please log in to reply
63 replies to this topic

#31 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 04 May 2020 - 04:37 AM

Cod liver oil; specifically vitamin A - is suppose to help with growing and maturing interneurons.  Through increase in reelin (?).   I don't have studies accessible but this thread turned to mostly speculation anyhow. I know multiple studies back this up, specifically, retinoic acid. Also, forskohilli is shown to help (turning S.C. to interneurons).  Again, no study for forskohilli.  It is all searchable if someone is serious about this in the future.    

 

valproic acid is suppose to work. I *believe* I read somewhere that this can be dangerous.

 

Also, there is something called dravet syndrome that has a ton of leads for this (this is where I got V.A.). 

 

 

Interneuron stack so far:

 

curcumin -  https://www.longecit...ring-the-brain/

 

Forskohilli - stem cells -> interneurons (need to link source)

 

Cod Liver Oil - Vitamin A & omega 3s. increase in reelin (?), studies show Retonic acid increases interneuron growth also see https://www.fasebj.o...upplement.lb275

 

CBD - See my posts for the study from this thread

 

Bacopa - I *believe* may help. Further research is needed

 

HDAC inhibitors - Black seed oil and Sodium butyrate (V.A. is a HDACi and I believe HDACi will help with interneurons albeit further research is required). Also, a keto diet will help (HDACi).

 

Tons of exercise - https://www.longecit...ring-the-brain/

 

 

 

You need lots of exercise.  The idea is to grow them back but in order for neurons to migrate at this stage it will require a lot of work regardless of the 'attack' you take. This why stroke patients have a hard time recovering (plus age and they also can't intensely exercise).  Cerebrolysin will help and Nardosinone (https://journals.plo...pone.0091260#s4). Nardosinone  requires more research, I think its a GABA(b) agonist.  Make sure there isn't any contradictions.  


Edited by Rorororo, 04 May 2020 - 05:37 AM.


#32 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 04 May 2020 - 06:53 AM

I should also note to stay away from any NMDA antagonist (agmatine, memantine..etc).  They have been shown to stop interneuron growth.  

 

Looks like bacopa will most likely help.  I am too lazy to connect the dots at this moment. 

 

 

My goal is to find a treatment that doesn't touch serotonin.  Looks like a lot of people are complaining about bacopa's motivation side effect.  I have no clue how it will be on a SSRI...unless someone plans on putting their life away for 1.5 months...further research is needed. 

 

Also found this:

cortical GABAergic interneurons is enhanced by the neurotrophic factors BDNF, NT-4, hepatocyte growth factor, and GDNF

 

 

Looks like Royal Jelly will be helpful :). I dont think grapefruit and CBD mixes well though.

 

 

I am also going to spend sometime and attack it differently (stay away from serotonin).  I believe Resveratrol might help too.  


Edited by Rorororo, 04 May 2020 - 07:52 AM.

  • Needs references x 1

sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#33 gamesguru

  • Guest
  • 3,465 posts
  • 428
  • Location:coffeelake.intel.int

Posted 05 May 2020 - 11:48 AM

anybody else with some perspective on noopept vs. dihexa here?

 

i heard noopept was good for being social and on top of yourself, but i read a lot of reports of fatigue and brain fog as well.  That's why i said be cautious.  Sometimes we underestimate just how mind-bending these substances are, especially some synthetic ones created for specific purposes.



#34 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 05 May 2020 - 07:10 PM

anybody else with some perspective on noopept vs. dihexa here?

 

i heard noopept was good for being social and on top of yourself, but i read a lot of reports of fatigue and brain fog as well.  That's why i said be cautious.  Sometimes we underestimate just how mind-bending these substances are, especially some synthetic ones created for specific purposes.

 

Dihexa might be a little extreme here.  yeah, it will work though. It is a powerful HGF modulator.  I am curious if there is a weaker and natural hgf modulator? I never heard of one. I know they're hgf inhibitor in existence (purple yams) and others

 

Noopept increases BDNF but I agree, cautious is key.  I heard those reviews coming from people that abused it 

 

 

Also, kudos on royal jelly. What a hidden gem!  I looked more into it and fell in love!  Definitely part of my personal daily stack.  Can I ask what brand you use? I know alot of people counterfeit it \ underdose it unfortunately. I would love to get my hands on legit and bulk royal jelly


Edited by Rorororo, 05 May 2020 - 07:14 PM.


#35 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 05 May 2020 - 09:47 PM

This is interesting:

 

https://www.mdpi.com.../19/11/3650/pdf

 

 

In SVZ regions, NPCs continuously differentiate into neuroblasts, and migrate into the granular cell layer or glomerular layers of olfactory bulb (OB), then differentiate into inhibitory interneurons or dopaminergic neurons [7]

 

 

TrkB deletion severely decreased the survival of newborn dopaminergic neurons but not interneurons in glomerular layers [43]. Interestingly, the specific loss of dopaminergic neurons was mirrored by a corresponding increase in the number of interneurons, highlighting essential roles of TrkB in balancing the incorporation of defined classes of adult-born neurons in the OB [43].

 

 

Could this be why that SSRI could increase interneurons from an adverse effect of increased serotonin? I will leave it to whomever to make the jump between the connection but *I* would avoid anything that touch dopamine. 

 

 

Also from:

 

https://prism.ucalga....pdf?sequence=1

 

 

It is thought that RGL quiescence is maintained through direct GABA signaling from parvalbumin-positive interneurons, and that GABA promotes survival of early stage NSCs (Song et al., 2012).

 

I know intranasal insulin works through TrkB and increases GABA.  This is all heavy speculation *but* it could be an angle of attack in avoidance of serotonin.  Perhaps intranasal insulin and noopept or 7,8 DHF? OR, better yet: Intranasal insulin and Chinese skull cap. I know C. skullcap increases BDNF and also works through GABA.  Plus the rest, royal jelly, curcumin...etc

 

 

Also, I would be so scared combing dihexa + SSRI.  That HPPD scared the crap out of me. I will never touch anything with serotonin drugs (just incase someone stumbles on this and gets ideas)


Edited by Rorororo, 05 May 2020 - 10:03 PM.


#36 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 06 May 2020 - 12:34 AM

CBD may interact with the other drugs metabolism (where I got grapefruit from).  Then you need to counteract the decrease in Gaba with Royal Jelly.  Bee pollen helps with glutamate toxicity.  Also maybe throw in L theanine?  So much work (to make it optimal that is)....

 

nardostachys is a GABA(b) agonist

C. Skull cap is a GABA(a) agonist 

 

I know intranasal insulin increases GABA.  Maybe still throw something else in (that makes sense in this stack)?   

 

I am thinking of Ashwaganda, 1) from here: https://www.longecit...ring-the-brain/

 

 

I am also thinking of pure thymoquinone (black seed oil).  I know BSO can increase serotonin tho, I don't know if pure thymoquinone will. I know its a HDACi and I *think* it can increase GABA.  

 

Taurine through out the day will also make sense. 

 

 

Lemon balm also seems interesting.  I will look more into it. I think ashwaganda, Taurine and theanine will make the most sense though. 


Edited by Rorororo, 06 May 2020 - 12:55 AM.


#37 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 06 May 2020 - 02:31 AM

Looks like im looking for a HDAC1 inhibitor from: https://onlinelibrar....1111/jnc.13773

 

Looks like thymoquinone is a HDAC - I inhibitor. Does it touch serotonin? I am not sure. 

Alcar *might* be one from: https://ashpublicati...bitors-In-Vitro

 

I spent too much time on this. I am sure I will come back to this later. 
 

 

interneuron stack so far (w/o touching serotonin system); pick your poison all this together will probably be overkill.  Maybe a combination throughout time might be best.  1 month with the stronger substance (noopept) then take it away the other month and add thymoquinone and so on

 

curcumin -  https://www.longecit...ring-the-brain/

 

Forskohilli - stem cells -> interneurons (need to link source)

 

Cod Liver Oil - Vitamin A & omega 3s. increase in reelin (?), studies show Retonic acid increases interneuron growth also see https://www.fasebj.o...upplement.lb275

 

Royal Jelly + Taurine + theanine  (might be over kill) - see previous posts for speculation 

 

HDAC inhibitors -  thymoquinone 

 

noopept - see previous posts

 

Intranasal insulin - see previous posts

 

Tons of exercise - https://www.longecit...ring-the-brain/

 

nardostachys &  C. Skull cap at night - see my previous posts for speculation

 


Edited by Rorororo, 06 May 2020 - 03:29 AM.


#38 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 06 May 2020 - 03:37 AM

Reference to NMDA antagonists: https://www.biorxiv....3371v1.full.pdf

I would stay away from them - they apparently lower interneurons. Alcar might be a HDAC I inhibitor?  There is a lot of jargon in the article I posted but I know it helps increase NGF and upregulates D1 receptors which forskohlii downregulates 

 

I would honestly just throw in bee pollen for the hell of it in that stack. https://www.ncbi.nlm...pubmed/28532421

 

 

EDIT: looks like thymoquinone does touch serotonin....

 

http://www.sjamf.eg....;aulast=Mahmoud

https://www.ncbi.nlm...pubmed/25207705

https://www.hilarisp...rats-32744.html

 

 

HDAC-I potential replacements:

Sulforaphane - https://www.frontier...2017.00121/full


Edited by Rorororo, 06 May 2020 - 04:01 AM.


#39 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 06 May 2020 - 04:47 AM

Found a list of natural HDACi (I wouldn't touch V.A):

https://www.ncbi.nlm...les/PMC5508980/

 

 

Looks like Luteolin is the best bet....but...a quick search on here shows Luteolin also does other stuff...

 

Butyrate is a HDAC class 1 inhibitor but a short lived one, 6 minutes IIRC....



#40 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 06 May 2020 - 05:25 AM

Looks like apigenin is the best choice.  It has a long half life too. 

 

 

Looks like it lowers dopamine, norepinephrine and serotonin less than luteolin:

https://www.ncbi.nlm...pubmed/19815045

 

 

Or you can say that luteolion  is.  Shorter half life so take it at night?  I wouldn't touch neurotransmitters, especially decrease them... luteolion is also a PDE4i.  

 

 

Hopefully someone can chime in bewteen luteolion & apigenin 


Edited by Rorororo, 06 May 2020 - 05:42 AM.


#41 gamesguru

  • Guest
  • 3,465 posts
  • 428
  • Location:coffeelake.intel.int

Posted 06 May 2020 - 12:10 PM

nardostachys is a GABA(b) agonist

C. Skull cap is a GABA(a) agonist

 

 

antagonists will fix downregulation,

 

ginseng.

 

 

Gen Pharmacol. 1994 Jan;25(1):193-9.

Interactions of ginsenosides with ligand-bindings of GABA(A) and GABA(B) receptors.

Kimura T1, Saunders PA, Kim HS, Rheu HM, Oh KW, Ho IK.

 

Abstract

1. Total saponin fraction decreased the affinity of specific [3H]muscimol binding without changes in Bmax. Ginsenoside Rb1 Rb2, Rc, Re, Rf and Rg1 inhibited the specific [3H]muscimol binding to the high-affinity site. 2. Total saponin fraction increased the affinity of specific [3H]flunitrazepam binding. Ginsenoside Re and Rf enhanced specific [3H]flunitrazepam binding. 3. Total saponin fraction decreased the affinity of specific [35S]TBPS binding without changes in Bmax. Ginsenosides did not affect specific or non-specific [35S]TBPS binding. 4. Total saponin fraction decreased the affinity of specific [3H]baclofen binding without changes in Bmax. Ginsenoside Rc inhibited specific [3H]baclofen binding.

 

 

bacopa.

 

J Biomed Sci. 2012; 19(1): 25.

Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

Jobin Mathew,1Savitha Balakrishnan,2Sherin Antony,2Pretty Mary Abraham,2 and CS Paulose2

Abstract Background

Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue.

Methods

In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated.

Results

Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABA, GABA, GABAB and GAD were down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance.

ConclusionsBacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.

 

 

ginkgo (less effective in my experience).

 

J Biol Chem. 2003 Dec 5;278(49):49279-85. Epub 2003 Sep 22.

Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABA(A) receptors.

Ivic L1, Sands TT, Fishkin N, Nakanishi K, Kriegstein AR, Strømgaard K.

Abstract

Glycine and gamma-aminobutyric acid, type A (GABA(A)) receptors are members of the ligand-gated ion channel superfamily that mediate inhibitory synaptic transmission in the adult central nervous system. During development, the activation of these receptors leads to membrane depolarization. Ligands for the two receptors have important implications both in disease therapy and as pharmacological tools. Terpene trilactones (ginkgolides and bilobalide) are unique constituents of Ginkgo biloba extracts that have various effects on the central nervous system. We have investigated the relative potency of these compounds on glycine and GABA(A) receptors. We find that most of the ginkgolides are selective and potent antagonists of the glycine receptor. Bilobalide, the single major component in G. biloba extracts, also reduces glycine-induced currents, although to a lesser extent. Both ginkgolides and bilobalide inhibit GABA(A) receptors, with bilobalide demonstrating a more potent effect. Additionally, we provide evidence that open channels are required for glycine receptor inhibition by ginkgolides. Finally, we employ molecular modeling to elucidate the similarities and differences in the structure of the terpene trilactones to account for the pharmacological properties of these compounds and demonstrate a striking similarity between ginkgolides and picrotoxinin, a GABA(A) and recombinant glycine alpha-homomeric receptor antagonist.

 

 

here's a thread where they talk a bit more about GABA-ergic supplements: https://www.longecit...at-affect-gaba/


  • Good Point x 1
  • WellResearched x 1

#42 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 07 May 2020 - 07:42 PM

antagonists will fix downregulation,

 

ginseng.

 

 

 

bacopa.

 

 

 

ginkgo (less effective in my experience).

 

 

 

here's a thread where they talk a bit more about GABA-ergic supplements: https://www.longecit...at-affect-gaba/

 

 

 

What do you think of this study on Royal Jelly?  It looks like it lowers neurotransmitters...I don't think its ideal for everyone:

http://www.jpccr.eu/...,71515,0,2.html

 

 

It seems like a miracle substance but I don't think it can be ideal for most.... I also found another study that said that re-informs this:

https://www.research...istar_male_rats

 

Bee pollen on the other hand might be useful at night because it contains Flavonoids which include: Luteolin

 

https://selfhacked.c...log/bee-pollen/


Edited by Rorororo, 07 May 2020 - 07:44 PM.


#43 gamesguru

  • Guest
  • 3,465 posts
  • 428
  • Location:coffeelake.intel.int

Posted 07 May 2020 - 07:51 PM

What do you think of this study on Royal Jelly?  It looks like it lowers neurotransmitters.

 

Bee pollen on the other hand might be useful at night because it contains Flavonoids which include: Luteolin

 

the first study doesn't say anything about lowering neurotransmitters?  All i'm seeing is that it fails to improve memory short-term, but it does immediately "modify" serotonin and dopamine?

 

i honestly think royal jelly is fine in smaller doses.  I buy a raw, local honey infused with royal jelly powder for about $8/lb.  Probably not as healthy as buying the fresh, refrigerated form of royal jelly, but it it's a lot more convenient.

 

the flavonoid luteolin isn't predominant in Bee Pollen, according to a verified source.  Quercetin is though, which is interesting, and it might help explain the anti-allergy hype.

Another group constituted phenolic compounds which amount to 1,6% on average. This group includes flavonoids, leukotrienes, catechins, and phenolic acids. Among flavonoids occurring in the pollen in 1,4%, there are mainly kaempferol, quercetin, and isorhamnetin, while in the group of phenolic acids, 0,2%, there is mainly chlorogenic acid [17].


Edited by gamesguru, 07 May 2020 - 07:53 PM.


#44 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 07 May 2020 - 08:07 PM

the first study doesn't say anything about lowering neurotransmitters?  All i'm seeing is that it fails to improve memory short-term, but it does immediately "modify" serotonin and dopamine?

 

i honestly think royal jelly is fine in smaller doses.  I buy a raw, local honey infused with royal jelly powder for about $8/lb.  Probably not as healthy as buying the fresh, refrigerated form of royal jelly, but it it's a lot more convenient.

 

the flavonoid luteolin isn't predominant in Bee Pollen, according to a verified source.  Quercetin is though, which is interesting, and it might help explain the anti-allergy hype.

 

 

 

They used word play to make the article sound more intriguing (i hate when scientists do this...). If you open the full article; you will actually see the tables they did and see how it actually lowered dopamine in almost all regions tested (expect for one) compared to the control group. 

 

It sounded like a miracle substance, no doubt about it.  I just don't think its for me anymore. I also don't think it will be good for inter-neurons (main topic) since another study showed it lowered GABA. Maybe another GDNF increasing substance will make do.  Granted, it's rat studies but its predominant to deter me. 

 

If I was someone serious about doing this...I would go here (it takes away the leg work):

https://mybiohack.co...-to-increase-it

 

find a strong GDNF increasing substance and make sure it doesn't have any adverse effects. This will take time of course. 


Edited by Rorororo, 07 May 2020 - 08:19 PM.


#45 gamesguru

  • Guest
  • 3,465 posts
  • 428
  • Location:coffeelake.intel.int

Posted 07 May 2020 - 08:23 PM

Is that bad though?  I looked and amphetamine and cocaine appear to do the opposite, raising DA and lowering DOPAC.  [See the figures beneath abstract]

 

Plus we know amphetamines bring short-term relief to Parkinson's symptoms, but in the long run make it worse.

 

Anything with an anti-dopaminergic effect will have an almost deliriant effect in higher doses.  And that's confirmed by the charts, showing 100mg/kg has big effect, which is 17mg/kg adjusted from rats.  That's still a lot, probably 3mg/kg is a lighter dose.  Approach it skeptically, try it in a variety of situation and states of health, and see what you think.



#46 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 07 May 2020 - 08:41 PM

Is that bad though?  I looked and amphetamine and cocaine appear to do the opposite, raising DA and lowering DOPAC.  [See the figures beneath abstract]

 

 

 

 

I don't know.  My guess is that it will be bad for neuro-typicals. I don't know enough though, I could be wrong.  That study is just out there, make the best decision for your self. Personally, I wouldn't take royal jelly.  I was pretty hyped on it, though.

 

I also found this on bee pollen:

https://www.jstage.j.../_html/-char/en

 

It looks like it has those HDACi I linked before.  Beware, they're monoamine transporter activators and will lower neurotransmitters


Edited by Rorororo, 07 May 2020 - 08:58 PM.


#47 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 07 May 2020 - 09:04 PM

Interneuron stack so far:

 

 

 

curcumin -  https://www.longecit...ring-the-brain/

 

Forskohilli - stem cells -> interneurons (need to link source)

 

ALCAR - see previous posts & https://mybiohack.co...-to-increase-it

 

Cod Liver Oil - Vitamin A & omega 3s. increase in reelin (?), studies show Retonic acid increases interneuron growth also see https://www.fasebj.o...upplement.lb275

 

Taurine - See previous posts (will raise GABA) &  https://www.longecit...ring-the-brain/

 

HDAC inhibitor (class I) -  Sulforaphane 

 

GDNF - PDE inhibitor or others (see:  https://mybiohack.co...-to-increase-it)

 

noopept - see previous posts

 

Intranasal insulin - see previous posts

 

Tons of exercise - https://www.longecit...ring-the-brain/

 

nardostachys &  C. Skull cap at night - see my previous posts for speculation

 


Edited by Rorororo, 07 May 2020 - 09:05 PM.


#48 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 07 May 2020 - 10:20 PM

Or, since a couple of things are in the stack already increase GDNF...you can look into a very weak and natural HGF modulator...

 

Like:

https://selfhacked.c...erb-death-trap/

 

Which shows increased HGF expression:

 

https://www.scienced...378874107003777

 

Its also toxic and you are playing with a bunch of pathways (w/ HGF)...its very risk...worth posting for speculation purposes. 


Edited by Rorororo, 07 May 2020 - 10:25 PM.


#49 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 08 May 2020 - 02:39 AM

Is that bad though?  I looked and amphetamine and cocaine appear to do the opposite, raising DA and lowering DOPAC.  [See the figures beneath abstract]

 

Plus we know amphetamines bring short-term relief to Parkinson's symptoms, but in the long run make it worse.

 

Anything with an anti-dopaminergic effect will have an almost deliriant effect in higher doses.  And that's confirmed by the charts, showing 100mg/kg has big effect, which is 17mg/kg adjusted from rats.  That's still a lot, probably 3mg/kg is a lighter dose.  Approach it skeptically, try it in a variety of situation and states of health, and see what you think.

 

 

I was wrong, in a way.  In general, increasing GDNF decreases dopamine. You can see that relationship from the general GDNF link I provided.  However, I think you can counter it by increasing another factor, like, BDNF.  Since nicotine apparently increases both and I know it increases dopamine...you can establish that relationship. Or, I think its an mao-i? However, I am sure someone can counter this somehow.   Why royal jelly decreases GABA?  I have no clue but i'm sure someone can find out with a little digging. 


Edited by Rorororo, 08 May 2020 - 02:40 AM.


#50 gamesguru

  • Guest
  • 3,465 posts
  • 428
  • Location:coffeelake.intel.int

Posted 08 May 2020 - 03:28 AM

However, I am sure someone can counter this somehow.

 

Why are you so convinced higher dopamine, higher GABA = better?  There was an avid poster here a while back named ScienceGuy who pushed the exact school of thought that raising neurotransmitters would often backfire in the long-term.  And I have to agree.  Look at people who do cocaine or benzos, compare that to people doing grapefruit or ginkgo and see who does better in the long run.

Modulatory effect of ginseng total saponin on dopamine release and tyrosine hydroxylase gene expression induced by nicotine in the rat.

Our results suggest that GTS may have an inhibitory action against nicotine-induced DA release in NA region and TH mRNA expression in VTA region. GTS may exert an potentiative effect on both c-fos and c-jun mRNA expression at NA region through inhibiting the release of DA in NA.

 

As for the boost, if it's needed, probably Japanese tea is good.  It has L-theanine which definitely boosts dopamine and serotonin, and goes best paired with caffeine.  The thing I can say about it if you decide to order l-theanine powder and caffeine pills what with shipping to Japan being difficult, is that the stuff is VERY POTENT.  Just do 50-75mg of each.  I would say that represents a good, finely ground, hotly brewed cup of Japanese tea.  You'll be missing the polyphenols, which also modulate serotonin, but the bulk of the effect in tea probably comes from caffeine and theanine.  This dose can be taken 2-3x throughout the day if needed.



#51 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 08 May 2020 - 03:53 AM

Why are you so convinced higher dopamine, higher GABA = better?  There was an avid poster here a while back named ScienceGuy who pushed the exact school of thought that raising neurotransmitters would often backfire in the long-term.  And I have to agree.  Look at people who do cocaine or benzos, compare that to people doing grapefruit or ginkgo and see who does better in the long run.

 

As for the boost, if it's needed, probably Japanese tea is good.  It has L-theanine which definitely boosts dopamine and serotonin, and goes best paired with caffeine.  The thing I can say about it if you decide to order l-theanine powder and caffeine pills what with shipping to Japan being difficult, is that the stuff is VERY POTENT.  Just do 50-75mg of each.  I would say that represents a good, finely ground, hotly brewed cup of Japanese tea.  You'll be missing the polyphenols, which also modulate serotonin, but the bulk of the effect in tea probably comes from caffeine and theanine.  This dose can be taken 2-3x throughout the day if needed.

 

 

Long term, yes. I would of course agree.  Short term, I would, disagree.  Some people need dopamine for focusing and motivation purposes.  There are pros and cons on everything and every approach.  Though, you can minimize the cons the best you can.

 

Then there is GABA for anxiety purposes.

 

 

That is why, in general, I am convinced higher dopamine, higher GABA = better.  It will be a better quality of life for some people.  Those people just need to take care of themselves more than others.   

 

I can be a vegetable in life, don't achieve anything that I wanted and live 110 years.  I also have a choice, I can live 90 years and achieve everything I want.  It just depends on the person.  

 

Don't take this personal, I know you are a huge fan of Royal Jelly. I don't mean to step on your toes with this.  Sometimes, people can influenced by the chandelier effect.  You have to pick and choose your poison. Whatever gets you what you want.  For me, royal jelly, may not be suited for my purposes. 


Edited by Rorororo, 08 May 2020 - 04:02 AM.


#52 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 11 May 2020 - 07:54 PM

Areas of interest:

 

Glutathione:

 

https://www.ncbi.nlm...pubmed/23140664

 

Gingseng *might* help by modulating Glutathione

 

 

 

Also, don't take a bunch of stuff in hopes of repair. A smart and strategic plan is needed.   I am just pointing out areas of interest. 


Edited by Rorororo, 11 May 2020 - 08:01 PM.


#53 gamesguru

  • Guest
  • 3,465 posts
  • 428
  • Location:coffeelake.intel.int

Posted 14 May 2020 - 02:37 AM

When Heraclitus put forth a counter-argument—by moving—Parmenides simply argued that just because his arm was in one place one second and in another place the next second, didn't mean that anything had moved.  Parmenides was a very annoying person to have lunch with.

 

2fMcd.jpg


Edited by gamesguru, 14 May 2020 - 02:51 AM.


#54 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 14 May 2020 - 05:13 AM

His hand didn't 'move' because position is a vector. It carries direction.  If you move 50 feet forward, your position will be positive 50 feet.  If you then move 30 feet back from that, then your position will be positive 20...and so on. Or, if you move 50 feet forward then 50 feet back then your position is 0, you did not move. Why you posted this? I don't know. 

 

 

When Heraclitus put forth a counter-argument—by moving—Parmenides simply argued that just because his arm was in one place one second and in another place the next second, didn't mean that anything had moved.  Parmenides was a very annoying person to have lunch with.

 

2fMcd.jpg

 



#55 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 06 June 2020 - 03:17 AM

Found a good article on generating interneurons! 

https://dx.doi.org/1.../2045-3701-3-19

 

According to that one....

 

You want to activate D1 receptors and deactivate D2.. So take out forskohilli ( I cant find the study but forskohili helped generate interneurons from S.C.)

 

 

As it again, stated:  HGF, BDNF and GDNF play a role. 

 

inositol is suppose to help Sulforaphane  in class- I inhibition ( i dont have a reference atm but its googable). However, I believe a hepatic dose of inositol will help activate D2 so perhaps 1 gram per dosage with Sulforaphane ?  Wild guess here btw. 

 

sulbutiamine seems worth to be investigated.  Should help activate D1

 

curcumin -  https://www.longecit...ring-the-brain/

 

sulbutiamine - Upregulates Dopamine D1

ALCAR - see previous posts & https://mybiohack.co...-to-increase-it

 

Cod Liver Oil - Vitamin A & omega 3s. increase in reelin (?), studies show Retonic acid increases interneuron growth also see https://www.fasebj.o...upplement.lb275

 

Taurine - See previous posts (will raise GABA) &  https://www.longecit...ring-the-brain/

 

HDAC inhibitor (class I) -  Sulforaphane w/ inositol 

 

GDNF - pick, lots of options

 

noopept - see previous posts

 

Intranasal insulin - see previous posts

 

Tons of exercise - https://www.longecit...ring-the-brain/

 

nardostachys &  C. Skull cap at night - see my previous posts for speculation

 

 

A little more organized:

 

 

Dopamine D1 (Upregulation, activation) R:

sulbutiamine; alcar 

 

HDAC inhibitor - Class I: 

Sulforaphane w/ inositol (double check the inositol)

 

Dopamine D2: (antagonist) R:

I wouldn't to be honest, unless its natural and safe... Also inositol might be counter-productive here

 

Neurotrophins R:

BDNF: Curcumin; Baicalin; Low-dose intranasal insulin (activates TrkB)

GDNF

HGF:

 

Cell migration: nardostachys; tons of exercise; Neurotrophins

 

Increase GABA: Baicalin (Chinese Skullcap); inositol; taurine; Low-dose intranasal insulin

 

reelin: Cod Liver Oil - Vitamin A & omega 3s. increase in reelin (?), studies show Retonic acid increases interneuron growth also see https://www.fasebj.o...upplement.lb275

 

 

 

Cavets:

 

Look more into sulbutiamine's mechanisms.

 

Sulforaphane w/ inositol (double check the inositol)

 

Double check if taurine makes sense here. 

 

Look more in nardostachys mechanisms.

 

 

Read the whole article or search for others methods to see if they have a factor that can induce production. Prozac is one possibility still but its a SSRI


Edited by Rorororo, 06 June 2020 - 03:50 AM.


#56 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 06 June 2020 - 06:39 AM

Looks like you want to upregulate KCC2

 

From:

 

 

 

To date, the molecular mechanisms that regulate the termination of interneuron migration in the cortex are largely unknown. However, Bortone and Polleux have shown that the potassium-chloride cotransporter KCC2 plays an integral role in terminating interneuron migration [196]. When interneurons are actively migrating, ambient GABA and glutamate initially stimulate the motility through activation of GABAA and AMPA/NMDA receptors. However, once interneurons reach the cortex, upregulation of KCC2 results in a hyperpolarization of membrane potential, thereby serving as a stop signal that interneurons are able to sense [196]. Further investigations should be performed to further elucidate the mechanisms underlying termination of migration.

 

 

Showing KCC2 down regulation produces seizures: https://www.ncbi.nlm...les/PMC5427808/

 

There is also more info about interneurons in that article. 

 

Then, https://www.frontier...2019.00048/full

 

States:

 

 

 

 

Recently, KCC2 down-regulation was also observed in conditions of reduced GABAergic inhibition in mature neurons (Heubl et al., 2017). 

 

 

https://epiphanyasd....-in-autism.html

 

This states intranasal insulin UPREGULATES KCC2 

 

5-ht2a activation upregulates KCC2 also

 

https://www.pnas.org/content/110/1/348

 

Zinc upregulates KCC2? 

https://www.ncbi.nlm...les/PMC3227684/

 

 

WAIT: looks like this guy did all the work for me :)

https://epiphanyasd....-for-retts.html


Edited by Rorororo, 06 June 2020 - 06:42 AM.


#57 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 06 June 2020 - 10:08 AM

Piceatannol:

 

From: https://www.longecit...53-deacetylase/

 

You see that Piceatannol is 3x more potent in SIRT activation than resverartrol. 

 

 

From: https://www.research...f_Neuronal_KCC2

 

The polyphenolic compound resveratrol is an allosteric activator of SIRT1 [82], and has beenextensively implicated in neuroprotection and anti-aging effects [118–120]. Its effect on KCC2 expressioncould potentially be explained. SLC12A5 transcription is regulated by a repressor element-1 (RE-1) sitein its 50regulatory region [121], and it has been reported that resveratrol could act via SIRT1 activationto downregulate the expression of RE1-silencing transcription factor/Neuron-restrictive silencer factor(REST/NRSF) [122]. The latter is a downstream target of SIRT1 

 

 

Piceatannol is also more water soluble than reservatrol and should have a higher BBB penetration.  It's getting late but I think thats your best bet in terms of KCC2 upregulation.  

 

 

Interneuron stack so far:

 

Dopamine D1 (Upregulation, activation) R:

sulbutiamine; alcar; Stepholidine is a natural D1 agonist and D2 antagonist R

 

Dopamine D2: (antagonist) R:

I wouldn't to be honest, unless its natural and safe... Also inositol might be counter-productive here BUT....Stepholidine is a natural D1 agonist and D2 antagonist R

 

HDAC inhibitor - Class I: 

Sulforaphane w/ inositol (double check the inositol)

 

Neurotrophins R:

BDNF: Curcumin; Baicalin; Low-dose intranasal insulin (activates TrkB)

GDNF:  Ashwaghada; Ziziphus Jujuba

HGF: Dihexa(?) - I think it's the only option 

 

Cell migration: nardostachys; tons of exercise; Neurotrophins

 

Increase GABA: Baicalin (Chinese Skullcap); inositol; taurine; Low-dose intranasal insulin; nardostachys; Ashwaghada; Ziziphus Jujuba

 

reelin: Cod Liver Oil - Vitamin A & omega 3s. increase in reelin (?), studies show Retonic acid increases interneuron growth also see https://www.fasebj.o...upplement.lb275

 

KCC2: low-dose intranasal insulin; piceatannol; Piperine

 

NKCC1 inhibitor: bumetanide; Astaxanthin

 

 
Wow, thats beautiful!  Almost everything is accessible online and almost all natural (expect dihexa...)

Edited by Rorororo, 06 June 2020 - 10:59 AM.


#58 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 06 June 2020 - 06:59 PM

 

Piceatannol:

 

From: https://www.longecit...53-deacetylase/

 

You see that Piceatannol is 3x more potent in SIRT activation than resverartrol. 

 

 

From: https://www.research...f_Neuronal_KCC2

 

 

Piceatannol is also more water soluble than reservatrol and should have a higher BBB penetration.  It's getting late but I think thats your best bet in terms of KCC2 upregulation.  

 

 

Interneuron stack so far:

 

 
Wow, thats beautiful!  Almost everything is accessible online and almost all natural (expect dihexa...)

 

 

Passion Flower might be good for NKCC1:

https://jneuroinflam...2974-018-1221-6

 

I am not sure what else it does though (edit: it works on the opioid system also)...

 

 

My logic for the inositol: 

 

 

Recently it was discovered that Class I HDACs require inositol phosphates such as inositol-tetraphosphate [Ins(1,4,5,6)P4 or IP4] for maximal activity [33]

 

Which is from: https://www.ncbi.nlm...les/PMC4394046/

 

 

 

I would use 7,8 DHF for BDNF as it upregulates KCC2 as well. 


Edited by Rorororo, 06 June 2020 - 07:21 PM.


#59 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 08 June 2020 - 08:49 AM

NGF increases NKCC1....https://www.scienced...006291X07011175

 

Note for KCC2, make sure you take resveratrol-derivatives during NKCC1 inhibition from: https://pubmed.ncbi....h.gov/32166573/.  If you choose to use it, that is.  I should also note it is from Ammonia, Ischemia and Trauma conditions. It should(?) be fine for most people. 

 

 

Interneuron stack so far, Should be final unless any contradicts still exist:

 

Dopamine D1 (Upregulation, activation) R:

sulbutiamine; Stepholidine is a natural D1 agonist and D2 antagonist R

 

Dopamine D2: (antagonist) R:

I wouldn't to be honest, unless its natural and safe... Also inositol might be counter-productive here BUT....Stepholidine is a natural D1 agonist and D2 antagonist R

 

HDAC inhibitor - Class I: 

Sulforaphane w/ inositol (double check the inositol)

 

Neurotrophins R:

BDNF: 7,8 DHF; Low-dose intranasal insulin (activates TrkB); Baicalin (Chinese Skullcap

GDNF:  Ashwaghada; Ziziphus Jujuba

HGF: Dihexa(?) - I think it's the only option 

 

Cell migration: tons of exercise; Neurotrophins

 

Increase GABA: Baicalin (Chinese Skullcap); inositol; taurine; Low-dose intranasal insulin;; Ashwaghada; Ziziphus Jujuba

 

reelin: Cod Liver Oil - Vitamin A & omega 3s. increase in reelin (?), studies show Retonic acid increases interneuron growth also see https://www.fasebj.o...upplement.lb275

 

KCC2: low-dose intranasal insulin; piceatannol; Pterostilbene; Piperine

 

NKCC1 inhibitor: bumetanide; Astaxanthin

 


Edited by Rorororo, 08 June 2020 - 08:51 AM.


sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#60 Rorororo

  • Topic Starter
  • Guest
  • 306 posts
  • 10
  • Location:America
  • NO

Posted 10 June 2020 - 10:40 PM

NGF increases NKCC1....https://www.scienced...006291X07011175

 

Note for KCC2, make sure you take resveratrol-derivatives during NKCC1 inhibition from: https://pubmed.ncbi....h.gov/32166573/.  If you choose to use it, that is.  I should also note it is from Ammonia, Ischemia and Trauma conditions. It should(?) be fine for most people. 

 

 

Interneuron stack so far, Should be final unless any contradicts still exist:

 

 

Edit: Ashwagnhda inhibits angiogenesis while Dihexa promotes angiogenesis

 

There is Naringin for GDNF then reservatrol should increase it (4x IIRC) and possibly reservatrol's derivatives will increase it too? I did a quick search and didn't find studies. 

 

Interneuron stack so far, Should be final unless any more contradictions still exist:

Quote

 

Dopamine D1 (Upregulation, activation) R:

sulbutiamine; Stepholidine is a natural D1 agonist and D2 antagonist R

 

Dopamine D2: (antagonist) R:

I wouldn't to be honest, unless its natural and safe... Also inositol might be counter-productive here BUT....Stepholidine is a natural D1 agonist and D2 antagonist R

 

HDAC inhibitor - Class I: 

Sulforaphane w/ inositol (double check the inositol)

 

Neurotrophins R:

BDNF: 7,8 DHF; Low-dose intranasal insulin (activates TrkB); Baicalin (Chinese Skullcap)

GDNF:  Naringin; reservatrol 

HGF: Dihexa(?) - I think it's the only option 

 

Cell migration: tons of exercise; Neurotrophins

 

Increase GABA: Baicalin (Chinese Skullcap); inositol; taurine; Low-dose intranasal insulin; Naringin

 

reelin: Cod Liver Oil - Vitamin A & omega 3s. increase in reelin (?), studies show Retonic acid increases interneuron growth also see https://www.fasebj.o...upplement.lb275

 

KCC2: low-dose intranasal insulin; piceatannol; Pterostilbene; Piperine

 

NKCC1 inhibitor: bumetanide; Astaxanthin


Edited by Rorororo, 10 June 2020 - 10:41 PM.





0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users