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BDNF overexpression induces learning and memory impairments in mice (too much of a good thing = bad thing)

bdnf lions mane

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#1 cjgymrat

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Posted 29 July 2012 - 06:36 PM


Over the past few months, I have developed a burgeoning interest in nootropics, and the implication of augmenting intelligence/ pursuing the NZT effect. My intent was to also ameliorate any brain damage I accrued in my years playing rugby, as well as excessively drinking.

About two months ago, through independent research, I learned about the mushroom lion's mane, or Hericium erinaceus, and it's numerous touted neuroregenerative and nootropic benefits. Soon later bought some Host Defense - Lion's Mane, and began a supplementing 4 grams of the extract daily (2 grams upon waking - 2 grams at night).

I have stuck this routine (with a few occasional breaks) and haven't noticed much with the exception of.

-Increased visual saturation
-Occasional itching
-Mild brain fog
-Slightly elevated anxiety (I am prone to OCD/ depression so this relationship could be spurious)

To get to the main thrust of this post, I recently came across this journal article.


Brain-derived neurotrophic factor (BDNF) overexpression in the forebrain results in learning and memory impairments

Abstract

In this study we analyzed the effect on behavior of a chronic exposure to brain-derived neurotrophic factor (BDNF), by analysing a mouse line overexpressing BDNF under the αCaMKII promoter, which drives the transgene expression exclusively to principal neurons of the forebrain. BDNF transgenic mice and their WT littermates were examined with a battery of behavioral tests, in order to evaluate motor coordination, learning, short and long-term memory formation. Our results demonstrate that chronicBDNFoverexpression in the central nervous system (CNS) causes learning deficits and short-term memory impairments, both in spatial and instrumental learning tasks. This observation suggests that a widespread increase in BDNF in forebrain networks may result in adverse effects on learning and memory formation.


-Perhaps BDNF overexpression (in an otherwise healthy 22 y/o) could attribute my lack of improvement in cognition/ subtle brain fog?

-Is 4 grams of lion's mane daily excessive?

-Perhaps this study bears some significance to any longecity users supplementing heavy with ALCAR/Lion's Mane and other BDNF precursors?

-Has anyone taken more than 4 grams of lion's mane for an extended period of time and noticed any nootropic benefits.

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#2 kevinseven11

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Posted 31 July 2012 - 04:43 AM

Lions mane was NGF promoter only I thought?
Very interesting though. How much of an effect is my question?

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#3 renfr

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Posted 31 July 2012 - 08:05 AM

Humm yes I think Lion's mane only increases NGF output and has nothing to do with BNDF.
BNDF overexpression leads to downregulation of receptors that's probably why it causes such symptoms but on the other you have to keep in mind that experiments on mice are always done with extreme doses therefore if you take normal doses of BNDF promoters it shouldn't be a problem. However if downregulation is a known problem then it should be cycled, 2 weeks on, 2 weeks off for example in order to allow receptors to stabilize.
4g is not excessive, it's about the dose you have to take that is between 2-5g if you're talking of pure powder and not the extract.
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#4 against_all_odds

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Posted 31 July 2012 - 04:18 PM

I used up to 10-20 grams of non-extracted lions mane and felt nothing from it. Then i tried an extract in much lower doses and after a few months i developed an extreme sensitivity to spicy foods and warm showers, which i attributed to the mushroom. So i doubt that its the cause of your problems.

Edited by against_all_odds, 31 July 2012 - 04:19 PM.


#5 victortsoi

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Posted 31 July 2012 - 04:34 PM

doesn't aniracetam increase BNDF?

#6 noopeptisgood

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Posted 01 August 2012 - 06:58 AM

I believe that NGF and BDNF stimulation goes hand in hand.
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#7 Flex

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Posted 03 October 2012 - 09:09 PM

I´ve tried the mushroom extract once and felt something similair.
I think the anixogenic effects are related through the kappa opioid agnism of the mushroom

Erinacine E is a potent agonist of the Kappa opioid receptor with potential hallucinogenic!
http://medicinal-mus...ceus-c-171.html

http://www.ncbi.nlm....pubmed/21531393

in addition i have read that a activation of kappa opioids (e.g kappa 2 opioid receptor) could cause Depersonalisation.

and it may be of note that the selective kappa opioid receptor agonist enadoline has been found to induce depersonalisation, although this was only one of numerous reported physical and psychological effects (Walsh et al, 2001).
http://apt.rcpsych.o...nt/11/2/92.full

dont missunderstand me, the mushroom has good benefits it was even tested against dementia.
but some people who are sensitive should take car of it.
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#8 golden1

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Posted 03 October 2012 - 09:21 PM

Weird it felt nothing at all like salvia(potent potent kappa opoid agonist). Salvia makes you forget everything for a short period of time, so that to me is extreme depersonalization.. probably why everyone hates it, but I found the crazyness to be very very interesting and the experiences to be worth it. Also, it had an anti-depressant effect the following days.

Lion's mane powder, I just get enhanced depth perception and color.. nothing alike really.

#9 Renegade

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Posted 03 October 2012 - 10:02 PM

I ordered some Lions Mane today which I was planning to take 2g a day.

I have been taking 1000mg of ALCAR and had decided to increase to 3000mg as I like the effects.

I also exercise and take curcumin daily.

Also been planning to add ashwaghanda.

After reading this, I'm wondering whether this is too much BNDF?

Edited by Renegade, 03 October 2012 - 10:19 PM.


#10 nidhogg

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Posted 04 October 2012 - 02:39 PM

You are misenterpreting the study results. It states chronic overexpression, which is most likely a result of TRKb receptor downregulation. Natural bdnf release is cycled, and the supplements increase the amplitude and not frequency

Take HGH for instance, growth hormone releasing tumours completely obliterates GH and GHRH receptors, while exercise that induces a greater amplitude of growth hormone release has no impact on sensitivity

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#11 kurdishfella

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Posted 06 August 2020 - 09:32 AM

I think too much BDNF being counterproductive has to do with you not using your mind/or brain by yourself to think. For example if you have too much testosterone but you just sit still and don't move, your muscles never learn to use what you have. In the case of too much neurotrophins it makes it so you don't have to even try hard to think so you never use your brain hard enough. But overall you want more than less of it.


Edited by kurdishfella, 06 August 2020 - 09:39 AM.






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