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NSI-189

nsi-189

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#721 Sholrak

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Posted 11 June 2013 - 04:27 PM

The role of hippocampus in the pathophysiology of bipolar disorder



Frey, Benicio N.a e; Andreazza, Ana C.a b; Nery, Fabiano G.c f g; Martins, Marcio R.d; Quevedo, Joãod; Soares, Jair C.h; Kapczinski, Flávioa

Abstract

Bipolar disorder (BD) is thought to be associated with abnormalities within discrete brain regions associated with emotional regulation, particularly in fronto-limbic-subcortical circuits. Several reviews have addressed the involvement of the prefrontal cortex in the pathophysiology of BD, whereas little attention has been given to the role of the hippocampus. This study critically reviews data from brain imaging, postmortem, neuropsychological, and preclinical studies, which suggested hippocampal abnormalities in BD. Most of the structural brain imaging studies did not find changes in hippocampal volume in BD, although a few studies suggested that anatomical changes might be restricted to the psychotic, pediatric, or unmedicated BD subgroups. Functional imaging studies showed abnormal brain activation in the hippocampus and its closely related regions during emotional, attentional, and memory tasks. This is consistent with neuropsychological findings that revealed a wide range of cognitive disturbances during acute mood episodes and a significant impairment in declarative memory during remission. Postmortem studies indicate abnormal glutamate and GABA transmission in the hippocampus of BD patients, whereas data from preclinical studies suggest that the regulation of hippocampal plasticity and survival might be associated with the therapeutic effects of mood stabilizers. In conclusion, the available evidence suggests that the hippocampus plays an important role in the pathophysiology of BD.




Exercise training increases size of hippocampus and improves memory

Author Affiliations

  • Edited* by Fred Gage, Salk Institute, San Diego, CA, and approved December 30, 2010 (received for review October 23, 2010)

Abstract

The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.




Citation



Database: PsycINFO
[ Journal Article ]
Size, shape, and orientation of neurons in the left and right hippocampus: Investigation of normal asymmetries and alterations in schizophrenia.
Zaidel, Dahlia W.; Esiri, Margaret M.; Harrison, Paul J.
The American Journal of Psychiatry, Vol 154(6), Jun 1997, 812-818.

Abstract

  • Examined whether left and right hippocampal neuronal size, shape, and orientation are normally asymmetrical or asymmetrically affected in schizophrenia. The authors examined postmortem tissue from the left and right hippocampus of 17 normal Ss (aged 22–84 yrs) and 14 Ss with schizophrenia (aged 28–83 yrs). The size, shape, and variability in orientation of pyramidal neurons in hippocampal subfields CA1-CA4 was measured. Both neuronal size and shape showed significant effects of diagnosis and a 3-way interaction between diagnosis, hemisphere, and subfield. Neurons of the schizophrenic Ss were smaller than those of the normal Ss in the left CA1, left CA2, and right CA3 subfields; their shape differed from that of the normal Ss in the left CA1, left subiculum, and right CA3 subfields. Neurons in the CA3 genu in the schizophrenic Ss were less variable on the right than on the left. In the normal Ss, except for larger neurons in the left than in the right CA2 subfield and some left-right differences in variability of neuronal orientation, no statistically significant asymmetries were observed. The data confirm that hippocampal neuronal size is decreased in schizophrenia and reveal that the shape of neurons is altered. (PsycINFO Database Record © 2012 APA, all rights reserved)


Edited by Sholrak, 11 June 2013 - 04:38 PM.

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#722 megatron

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Posted 11 June 2013 - 05:03 PM

When I had extremely good cardio (two years ago), I remember I noticed a little bit better recall. So if I saw this improvement from only a 2% increase, we should definitely have high hopes of what ten times (ore more) that could imply...

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#723 lostfalco

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Posted 11 June 2013 - 05:08 PM

@Bion Alex Howard
Yes I was thinking the same considering log our Supplements and brain training behaviour to get some quantifible data...
I for one will do it... hopefully other NSI-users will do the same..
Speaking of Supplements... I heard that Blueberrys are very helpful strenghten neuron signals and overall brain function...


I am quite fond of this study:

http://www.ncbi.nlm....ubmed/22569815/

I go through a 3lb bag of frozen Blueberries every week along with 2 Tbsp of raw Cacao powder a day.


I've been looking into supplementing with flavanoids lately. Have you tried this or do you have any thoughts here?

#724 Metagene

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Posted 11 June 2013 - 06:42 PM

@Bion Alex Howard
Yes I was thinking the same considering log our Supplements and brain training behaviour to get some quantifible data...
I for one will do it... hopefully other NSI-users will do the same..
Speaking of Supplements... I heard that Blueberrys are very helpful strenghten neuron signals and overall brain function...


I am quite fond of this study:

http://www.ncbi.nlm....ubmed/22569815/

I go through a 3lb bag of frozen Blueberries every week along with 2 Tbsp of raw Cacao powder a day.


I've been looking into supplementing with flavanoids lately. Have you tried this or do you have any thoughts here?


I'm generally against taking vitamins and supplements for nutrients that can be obtained through proper diet. Flavanoid supplementation appears to be a bad idea.

http://www.berkeley....09/19_flav.html

I do take Ginkgo Biloba and Cacao daily as a part of my stack. You could look into those or possibly green tea.


#725 lostfalco

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Posted 11 June 2013 - 07:18 PM

@Bion Alex Howard
Yes I was thinking the same considering log our Supplements and brain training behaviour to get some quantifible data...
I for one will do it... hopefully other NSI-users will do the same..
Speaking of Supplements... I heard that Blueberrys are very helpful strenghten neuron signals and overall brain function...


I am quite fond of this study:

http://www.ncbi.nlm....ubmed/22569815/

I go through a 3lb bag of frozen Blueberries every week along with 2 Tbsp of raw Cacao powder a day.


I've been looking into supplementing with flavanoids lately. Have you tried this or do you have any thoughts here?


I'm generally against taking vitamins and supplements for nutrients that can be obtained through proper diet. Flavanoid supplementation appears to be a bad idea.

http://www.berkeley....09/19_flav.html

I do take Ginkgo Biloba and Cacao daily as a part of my stack. You could look into those or possibly green tea.


Thanks for the link and recommendations! I'm in the very early stages of research on flavonoids. I appreciate the input.

Quick question...it sounds like they are against extremely high doses of flavonoids and unknown toxins in unregulated flavonoid supplements. Couldn't these concerns be solved by simply finding a good supplement company and not taking too much? Are there synergistic elements in foods (blueberries, etc.) that must be taken simultaneously to get the effects?

#726 Metagene

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Posted 11 June 2013 - 11:03 PM

Yeah in normal amounts I don't see the harm. You'd probably miss out on other compounds contained in whole food but nothing indicates the benifits of increased flavonoid consumption would some how be rendered inert by pure supplementation. Again not my M.O.

#727 Sholrak

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Posted 12 June 2013 - 05:34 AM

Chairofgold had in his stack a cup of blueberries. After 5 days he noticed to laugh more. He did noticed to think younger. If you take that laughting is the best medicine into account i bet blueberrys could be one the most powerful natural antioxidanton earth, am I right?
Sure it does something in the hippocampus too.

#728 Xenix

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Posted 12 June 2013 - 05:49 AM

Chairofgold had in his stack a cup of blueberries. After 5 days he noticed to laugh more. He did noticed to think younger. If you take that laughting is the best medicine into account i bet blueberrys could be one the most powerful natural antioxidanton earth, am I right?
Sure it does something in the hippocampus too.


Snake oil.
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#729 Psionic

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Posted 12 June 2013 - 08:51 AM

How would you say one can cheat at dnb ?


Chunking - or in other words remembering the whole or part of a sequence of stimuli as a string so its easier to hit higher levels and thus you dont use manipulation needed for stressing WM.
Its somewhat hard to unlearn once you use it as a strategy, mental math seems to be deprived of this issues :)
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#730 Sholrak

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Posted 12 June 2013 - 04:51 PM

Chairofgold had in his stack a cup of blueberries. After 5 days he noticed to laugh more. He did noticed to think younger. If you take that laughting is the best medicine into account i bet blueberrys could be one the most powerful natural antioxidanton earth, am I right?
Sure it does something in the hippocampus too.


Snake oil.


Say to him.

#731 motorcitykid

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Posted 13 June 2013 - 05:08 AM

I've tried it several times (maybe 30 times ) and can't seem to go beyond D3b approx 75%. I'm pretty shure this is my plateau. Almost d4b.


I am going rather with mental math, multiplying two three-digits seems as such a good target.. DNB is cheatable and very individual. Maybe PASAT variation can be considerable.

There will be an attempt to make some decent WM game based on latest research in music field.. (right after NSI delivery :))


Do you experience any issues with audio on this website, as in, there isn't any? There isn't any sound on any of the brain games I tried (Db and mental math) even though the volume is completely turned up on my computer and on the webpage. I have windows 8 and I'm wondering if maybe brainscale.net isn't compatible. I sent them an email a few days ago but haven't heard back yet.

#732 Metagene

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Posted 13 June 2013 - 07:01 AM

I can't wait to get our experiment underway! My scale's LCD quit so I need a new one very soon. I'm taking another stab at learning the Major/peg system in hopes of overcoming overall cognitive weakness and to help retain a little Russian during the trial.

Anyway off to the grind. *sigh*

Edited by Metagene, 13 June 2013 - 07:08 AM.


#733 MetaMind

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Posted 13 June 2013 - 07:57 PM

Ok 5 weeks should be over now...
ScienceGuy do you ve any update on the shipping status?
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#734 brand2

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Posted 13 June 2013 - 09:47 PM

+1 any update?
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#735 axonopathy

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Posted 13 June 2013 - 11:47 PM

It's been mentioned in this thread that SSRI's upregulate hippocampal neurogenesis and alter hippocampal morphology; yet many patients feel impaired cognitively (e.g., word finding problems) on SSRIs. Is it possible that enhanced neurogenesis (which already occurs only in very restricted brain regions - mostly olfactory bulb) will not confer any cognitive benefits?

I also just read a paper disputing that neurogenesis even occurs on the grounds that glia (which can divide) were misidentified as neurons. I think they radiolabel nucleotides and look at their uptake in the brain and count the number of putative nascent neurons, and the authors were arguing that the signal was arising from astrocytes, microglia, etc.

Are there any plans for a future group purchase of NSI-189 that I might be able to partake in?

#736 megatron

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Posted 14 June 2013 - 02:54 PM

I've tried it several times (maybe 30 times ) and can't seem to go beyond D3b approx 75%. I'm pretty shure this is my plateau. Almost d4b.


I am going rather with mental math, multiplying two three-digits seems as such a good target.. DNB is cheatable and very individual. Maybe PASAT variation can be considerable.

There will be an attempt to make some decent WM game based on latest research in music field.. (right after NSI delivery :))


I totally agree with you. Mental math is something everyone should do throughout this trial. I just tested the game you referred to, and I had not idea I was that lousy at mental math.

#737 paul

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Posted 14 June 2013 - 05:16 PM

I keep checking this post, very excited to be starting this soon. I have been off all nootropics since end of my exams and hope to start this one before my new job begins end of July. I still have plenty of cerebrolysin left and may add this in depending on how I feel a week or two into the trial. If there is a second group buy I'd be happy to put my name down as I would ideally like to take a higher dose, as I find for most meds I need more than the average user to notice efficacy, perhaps overactive CYP450s in my liver from extensive nootropic use for many years.
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#738 daouda

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Posted 15 June 2013 - 02:44 AM

perhaps overactive CYP450s in my liver from extensive nootropic use for many years.


Is this possible? Can one upregulate his liver's metabolic enzyme systems with chronic intake of specific substrates? I doubt it, but if this is true this is a huge piece of info IMO, could someone with good pharmacology knowledge (niner?) please come and enlighten us about this? Thx

Edited by daouda, 15 June 2013 - 02:46 AM.


#739 Metagene

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Posted 15 June 2013 - 05:20 AM

Ask and you shall receive!

http://www.longecity...e-p-450-system/
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#740 megatron

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Posted 15 June 2013 - 07:49 PM

I hope the reason ScienceGuy hasn't been active in three days, is that he is busy packing and shipping the drug to the participants. However, if this is the case, it's strange that he hasn't even made time for announcing his retrieval of the drug. After all, the synthesis should have been finalized over a week ago, and shipping from "you know where" to the UK shouldn't take more than a week. It would be great if there at least could be some kind of update from either sunshinefrost or ScienceGuy.
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#741 IA87

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Posted 15 June 2013 - 07:58 PM

ScienceGuy seems like a reputable character to me, considering his past contributions to the community (e.g., sending out coluracetam samples). I would not worry.
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#742 izan82

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Posted 16 June 2013 - 12:39 AM

I hope the reason ScienceGuy hasn't been active in three days, is that he is busy packing and shipping the drug to the participants. However, if this is the case, it's strange that he hasn't even made time for announcing his retrieval of the drug. After all, the synthesis should have been finalized over a week ago, and shipping from "you know where" to the UK shouldn't take more than a week. It would be great if there at least could be some kind of update from either sunshinefrost or ScienceGuy.

take it easy man, you sound very desperate. scienceguy is legit, just be patient.
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#743 Sholrak

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Posted 16 June 2013 - 01:42 AM

Science Guy is great, sure he is doing his experiments with NSI-189. Very exciting times :)

I cannot imagine a better benefit as having your hippocampus "washed and reseted". If this comes with near zero secondary effects, it could be the cure to soo much problems. to so much suffer.

I think hippocampus is bigger in humans comparing to other species. It's the part of the brain which has let beings like us converting the fight or flight entire mechanism in language, speaking, learning, socializing. etc.
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#744 daouda

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Posted 16 June 2013 - 05:45 AM

Ask and you shall receive!

http://www.longecity...e-p-450-system/

Ok so apparently I haven't been clear enough, my bad. I'm perfectly aware that CY450 enzymes groups are upregulated with intake of their specific substrates, my question was can the chronic intake of certain substances for a long period (years) leave one with the corresponding CYP450 enzyme sub-group upregulated for a long time or even permanently, even after discontinuation of the said substance? I think that's what was implied in Paul's post above mine. I doubt this could be, but I'd like to get confirmation by someone with good pharmacology knowledge such as Niner, as this would be huge for us chronic supplement users.

#745 ScienceGuy

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Posted 16 June 2013 - 06:55 AM

UPDATE:

Hi Everyone,

Sorry for it being a while since I last posted an update... I have been offline for a bit due to being crazy busy with work commitments and the like... I've quite literally been doing 18-hour days and sometimes longer than that ;)

When I last checked in with the lab everything was proceeding nicely, but I will check in now for an up-to-date update, and post the details on this board as soon as I get a reply :)

Regarding the TIME FRAME, please kindly note that the lab informed me they would be proceeding with the order on MONDAY 6th MAY and that once they received delivery of all the raw materials required for completing the synthesis the lead time to complete the synthesis would be approximately 5 weeks. Therefore, one needs to allow not only for the time taken for the lab to source, order and receive delivery of all the raw materials, but also the possibility that it might take them a bit longer than they originally estimated to achieve the desired quality of product, namely >=99.9% PURITY.

Tomorrow is MONDAY 17th JUNE, which is only 6 WEEKS since the order start date, hence I expect it is going to be a minimum of a couple of weeks before the lab is ready to ship the product to me. I just wanted to put this out there to facilitate everyone having a realistic understanding of the ETA on this.

Thank you kindly for your patience ;)

EDIT: I should add that as with all instances of Custom Synthesis it is my intention to have the product independently tested and confirmed via a reputable third party laboratory in the UK. However, please kindly note that this will be done at no charge to any of you and I will use material taken from my own share of NSI-189; furthermore, I will do this in parallel with shipping everyone their quantities so as not to delay matters. :)

Edited by ScienceGuy, 16 June 2013 - 07:07 AM.

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#746 Metagene

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Posted 16 June 2013 - 12:40 PM

Ask and you shall receive!

http://www.longecity...e-p-450-system/

Ok so apparently I haven't been clear enough, my bad. I'm perfectly aware that CY450 enzymes groups are upregulated with intake of their specific substrates, my question was can the chronic intake of certain substances for a long period (years) leave one with the corresponding CYP450 enzyme sub-group upregulated for a long time or even permanently, even after discontinuation of the said substance? I think that's what was implied in Paul's post above mine. I doubt this could be, but I'd like to get confirmation by someone with good pharmacology knowledge such as Niner, as this would be huge for us chronic supplement users.


Oh sorry my mistake.

I appreciate the update ScienceGuy. No worries :)


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#747 Rior

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Posted 16 June 2013 - 06:43 PM

"There are 65 users reading this topic" MSN and Bing.

You serious? How in the hell did we get this much attention?

#748 phil8462643

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Posted 17 June 2013 - 02:41 PM

"There are 65 users reading this topic" MSN and Bing.

You serious? How in the hell did we get this much attention?

from us using the same keywords and phrases people search for over and over! Mentioning enn zhi tea surely must do the trick! thousands of people out there reading this who want nothing more than to take over markets and become mayor like that actor from a hangover! off topic but the first half of that flick rules. he would have been much cooler as a bestselling author. I hope when we do find it, if we do, it dosent turn us all into greedy f*kers like dude from a hangover!

#749 spookytooth

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Posted 17 June 2013 - 03:34 PM

Let us all not forget that Limitless was FICTION. It is highly unlikely that a substance like that will ever come into existence. This does in no way mean that nootropics are not worthwhile.

"There are 65 users reading this topic" MSN and Bing.

You serious? How in the hell did we get this much attention?

from us using the same keywords and phrases people search for over and over! Mentioning enn zhi tea surely must do the trick! thousands of people out there reading this who want nothing more than to take over markets and become mayor like that actor from a hangover! off topic but the first half of that flick rules. he would have been much cooler as a bestselling author. I hope when we do find it, if we do, it dosent turn us all into greedy f*kers like dude from a hangover!


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#750 megatron

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Posted 17 June 2013 - 04:30 PM

Let us all not forget that Limitless was FICTION. It is highly unlikely that a substance like that will ever come into existence. This does in no way mean that nootropics are not worthwhile.

"There are 65 users reading this topic" MSN and Bing.

You serious? How in the hell did we get this much attention?

from us using the same keywords and phrases people search for over and over! Mentioning enn zhi tea surely must do the trick! thousands of people out there reading this who want nothing more than to take over markets and become mayor like that actor from a hangover! off topic but the first half of that flick rules. he would have been much cooler as a bestselling author. I hope when we do find it, if we do, it dosent turn us all into greedy f*kers like dude from a hangover!


I doubt that a single substance can do that as well, but one should never underestimate future technology. I think it is rather likely that we (or some) may become as intelligent as "Eddie Morra", though from a range of drugs, each having different effects on the brain.
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