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Dec 8 2016 02:05am
Saw this on the front page of reddit and found it interesting .

https://peerj.com/articles/2727/

I'm not very scienc-y, why would the rapid division of neural progenitors be a good thing? Does that mean ayahuasca could eventually be used as an over the counter anti-depressant or other medical uses?

According to google, neural progenitors divide a limited number of times. Why would someone want to speed that up?

Abstract:

Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we

investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase

(DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is

a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

This post was edited by Shakti on Dec 8 2016 02:11am
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Dec 8 2016 02:07am
Perhaps
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Dec 8 2016 02:53am
Most psychedelic drugs has the potential to help with anxiety and depression since they overflood you with seratonin.
I remember one of my teachers talked about how psychedelic drugs where often discussed amongst psychologist and how it could be a good idea for depressed patients since they allow you to ''kill your ego'', this was of course under controlled dose/environment.

But the problem is people who use it by themselves and take quite a lot, the possibility of hallucinations can make it worse and the backlash when the trip is over can make you more tired and depressed for a few days.
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Dec 8 2016 06:07am
Quote (Shakti @ Dec 8 2016 04:05am)
Saw this on the front page of reddit and found it interesting .

https://peerj.com/articles/2727/

I'm not very scienc-y, why would the rapid division of neural progenitors be a good thing? Does that mean ayahuasca could eventually be used as an over the counter anti-depressant or other medical uses?

According to google, neural progenitors divide a limited number of times. Why would someone want to speed that up?

Abstract:

Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we

investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase

(DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is

a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.


Neural progenitor cells are cells that can form new neurons. The common theory is that after development, the number of neurons in the body becomes fixed and neuronal somas that die will not naturally be replaced. That is why brain damage can be so permanently devastating, neuronal progenitor cells only divide during development and will not replace dead neurons in adults under normal circumstances. If a compound can act on the brain to stimulate further division of neural progenitors that has far reaching implications
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Dec 8 2016 01:52pm
Not surprising, this is a known effect of MAOIs. The issue is their abundance of side effects, however, especially things like vomiting, egregious nausea, and so on. It has implications for depression and various co-morbidities because they're thought to cause gradual hippocampal atrophy, perpetuating depression/loss of emotional control, elevating glucocorticoids for other deleterious effects, and promoting cognitive decline & memory decay. But again, we know this to be the case from MAOIs, we just can't administer them due to adverse effects. Perhaps the specific molecule (DYRK1A) can be a novel target to bypass the effects of raising monoamine transmitter concentration, though, and still achieve neurogenesis.

As for a fixed number of divisions, etc, that's nonsense. Neurogenesis occurs throughout our lifetimes, albeit at a gradually slower pace. Further, it would have zero implications for normal replacement of deceased neurons in other areas of the brain, sans those few areas that we know encompass our few neurogenic niches (subgranular zone to DG of hippocampus, and subventricular zone to olfactory bulb, as well to the striatum). If we're talking about replacing neuronal death, such as with Parkinson's disease to exemplify the issue, we would need to either learn to induce neurogenesis, and then also specific migration and induction into that sub-tissue, or learn to manipulate stem cells to differentiate how we please (we have) and inject them specifically. Certainly, both avenues have merit, but there's far more progress done heretofore in the latter, and it also seems far more plausible due to specificity, etc. That would of course by extension be applicable to other areas, such as cortical ones with strokes, etc. Now, coming back to the issue of inducing neurogenesis to happen with greater celerity and w/ more magnitude, I think it's certainly debatable how appreciable the atrophy of brain tissues under depression, chronic stress, etc, really is. What I mean is - differentiating between neurogenesis and synaptogenesis/synaptic contact. There seems to be more evidence that it's more-so dendritic retraction (as opposed to arborization), and pruning of synapses in general, than it is specific death of neurons or loss of neurogenesis. For a quick example of how robust this can be (as it may not be intuitive), what appears to antecede schizophrenia is a massive pruning of the cortex, enough to be measured as an actual thinning - all purely from loss of synaptic contact. This ofc occurs as a teen, in a measurable way, but the process seems to get carried away in those afflicted, hence symptoms beginning late adolescence/early adulthood. Back to the point, I just didn't want too much emphasis on inducing neurogenesis to be placed, albeit it still may be therapeutic. MAOIs, various antidepressants, ketamine (experimental antidepressant inducing its effects in an extremely short time-frame due to rapid increased AMPA conduction in the PFC, causing synaptogenesis), etc, all induce this effect in some way.
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Dec 8 2016 02:27pm
Quote (PlaaD @ Dec 8 2016 03:53am)
Most psychedelic drugs has the potential to help with anxiety and depression since they overflood you with seratonin.
I remember one of my teachers talked about how psychedelic drugs where often discussed amongst psychologist and how it could be a good idea for depressed patients since they allow you to ''kill your ego'', this was of course under controlled dose/environment.

But the problem is people who use it by themselves and take quite a lot, the possibility of hallucinations can make it worse and the backlash when the trip is over can make you more tired and depressed for a few days.


serotonin is overrated

iso dopamine
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Dec 8 2016 04:32pm
I learned a lot in this thread.. wow.

A lot to process in here.

This post was edited by Shakti on Dec 8 2016 04:32pm
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Dec 8 2016 07:37pm
Quote (shane_is_a_balla @ Dec 8 2016 03:52pm)
Not surprising, this is a known effect of MAOIs. The issue is their abundance of side effects, however, especially things like vomiting, egregious nausea, and so on. It has implications for depression and various co-morbidities because they're thought to cause gradual hippocampal atrophy, perpetuating depression/loss of emotional control, elevating glucocorticoids for other deleterious effects, and promoting cognitive decline & memory decay. But again, we know this to be the case from MAOIs, we just can't administer them due to adverse effects. Perhaps the specific molecule (DYRK1A) can be a novel target to bypass the effects of raising monoamine transmitter concentration, though, and still achieve neurogenesis.

As for a fixed number of divisions, etc, that's nonsense. Neurogenesis occurs throughout our lifetimes, albeit at a gradually slower pace. Further, it would have zero implications for normal replacement of deceased neurons in other areas of the brain, sans those few areas that we know encompass our few neurogenic niches (subgranular zone to DG of hippocampus, and subventricular zone to olfactory bulb, as well to the striatum). If we're talking about replacing neuronal death, such as with Parkinson's disease to exemplify the issue, we would need to either learn to induce neurogenesis, and then also specific migration and induction into that sub-tissue, or learn to manipulate stem cells to differentiate how we please (we have) and inject them specifically. Certainly, both avenues have merit, but there's far more progress done heretofore in the latter, and it also seems far more plausible due to specificity, etc. That would of course by extension be applicable to other areas, such as cortical ones with strokes, etc. Now, coming back to the issue of inducing neurogenesis to happen with greater celerity and w/ more magnitude, I think it's certainly debatable how appreciable the atrophy of brain tissues under depression, chronic stress, etc, really is. What I mean is - differentiating between neurogenesis and synaptogenesis/synaptic contact. There seems to be more evidence that it's more-so dendritic retraction (as opposed to arborization), and pruning of synapses in general, than it is specific death of neurons or loss of neurogenesis. For a quick example of how robust this can be (as it may not be intuitive), what appears to antecede schizophrenia is a massive pruning of the cortex, enough to be measured as an actual thinning - all purely from loss of synaptic contact. This ofc occurs as a teen, in a measurable way, but the process seems to get carried away in those afflicted, hence symptoms beginning late adolescence/early adulthood. Back to the point, I just didn't want too much emphasis on inducing neurogenesis to be placed, albeit it still may be therapeutic. MAOIs, various antidepressants, ketamine (experimental antidepressant inducing its effects in an extremely short time-frame due to rapid increased AMPA conduction in the PFC, causing synaptogenesis), etc, all induce this effect in some way.


i feel like you comment when theres a legit scientific discussion everytime. but otherwise i wonder where u gone to lol

but somehow u know when these threads arise

This post was edited by noob_whacker on Dec 8 2016 07:37pm
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Dec 9 2016 12:02pm
Quote (noob_whacker @ Dec 8 2016 09:37pm)
i feel like you comment when theres a legit scientific discussion everytime. but otherwise i wonder where u gone to lol

but somehow u know when these threads arise



This forum has sucked for some time now. I get on very sporadically, for maybe 5m each time, and the lack of general activity means I see all new threads immediately lol. I also hardly click any of them so that helps.
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Dec 9 2016 12:11pm
Quote (shane_is_a_balla @ Dec 8 2016 03:52pm)
Not surprising, this is a known effect of MAOIs. The issue is their abundance of side effects, however, especially things like vomiting, egregious nausea, and so on. It has implications for depression and various co-morbidities because they're thought to cause gradual hippocampal atrophy, perpetuating depression/loss of emotional control, elevating glucocorticoids for other deleterious effects, and promoting cognitive decline & memory decay. But again, we know this to be the case from MAOIs, we just can't administer them due to adverse effects. Perhaps the specific molecule (DYRK1A) can be a novel target to bypass the effects of raising monoamine transmitter concentration, though, and still achieve neurogenesis.

As for a fixed number of divisions, etc, that's nonsense. Neurogenesis occurs throughout our lifetimes, albeit at a gradually slower pace. Further, it would have zero implications for normal replacement of deceased neurons in other areas of the brain, sans those few areas that we know encompass our few neurogenic niches (subgranular zone to DG of hippocampus, and subventricular zone to olfactory bulb, as well to the striatum). If we're talking about replacing neuronal death, such as with Parkinson's disease to exemplify the issue, we would need to either learn to induce neurogenesis, and then also specific migration and induction into that sub-tissue, or learn to manipulate stem cells to differentiate how we please (we have) and inject them specifically. Certainly, both avenues have merit, but there's far more progress done heretofore in the latter, and it also seems far more plausible due to specificity, etc. That would of course by extension be applicable to other areas, such as cortical ones with strokes, etc. Now, coming back to the issue of inducing neurogenesis to happen with greater celerity and w/ more magnitude, I think it's certainly debatable how appreciable the atrophy of brain tissues under depression, chronic stress, etc, really is. What I mean is - differentiating between neurogenesis and synaptogenesis/synaptic contact. There seems to be more evidence that it's more-so dendritic retraction (as opposed to arborization), and pruning of synapses in general, than it is specific death of neurons or loss of neurogenesis. For a quick example of how robust this can be (as it may not be intuitive), what appears to antecede schizophrenia is a massive pruning of the cortex, enough to be measured as an actual thinning - all purely from loss of synaptic contact. This ofc occurs as a teen, in a measurable way, but the process seems to get carried away in those afflicted, hence symptoms beginning late adolescence/early adulthood. Back to the point, I just didn't want too much emphasis on inducing neurogenesis to be placed, albeit it still may be therapeutic. MAOIs, various antidepressants, ketamine (experimental antidepressant inducing its effects in an extremely short time-frame due to rapid increased AMPA conduction in the PFC, causing synaptogenesis), etc, all induce this effect in some way.


Dead neural tissue is dead tissue. If you destroy the soma, it's not coming back. You can damage or sever axons and they will regenerate but once the cell body is dead the neuron is dead. Unless by neurogenesis you are referring to the healing of axons. Why do you think stroke survivors have such permanent functional loss? The cortex is highly plastic and the remaining tissue will rearrange it's functional organization but once neurons die they are dead and not replaced
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