dasitmane

Bit of an idea for possible CURE. Has some weight to it.

632 posts in this topic

No, the article clearly shows that the excitotoxity is a result from 5htp2a receptor activation.

did you even read the study?

Edited by dasitmane
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Pretty much puts the nail in the coffin for me at this point. We know have numerous studies showing proof of cell death from multiple hallucinogens. Now how we get this information to the general public is the real question...

I don't get why the 5htp2a receptor needs to be activated in order for the cell death to occur though. That's serotonin, correct? 

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On 2/13/2018 at 8:04 PM, K.B.Fante said:

Pretty much puts the nail in the coffin for me at this point. We know have numerous studies showing proof of cell death from multiple hallucinogens. Now how we get this information to the general public is the real question...

I don't get why the 5htp2a receptor needs to be activated in order for the cell death to occur though. That's serotonin, correct? 

Yah, I'm not exactly sure either to be honest. But its clearly the link.

I do wish this information was publicized instead of the ridiculous researchers investigating the "pros" of hallucinogens, if this information were available I never would have done them.

Edited by dasitmane
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Today, I'm the bearer of bad news. This news was unforeseen, and is all in all, quite crushing. Looking through regenerative videos of salamanders today, I found and noticed that regeneration wasn't completely up to par. That even though the limb might regrow. It didn't grow back perfectly in most cases. Which had me wondering more about neuronal regeneration, and after just a little bit of reading, the reality of all of this has really, finally, and sadly, fallen in to place. Unless someone can prove me wrong.

I'm actually so depressed about this, that Ill hardly elaborate like I usually do. But to put it plainly, the brain consists of neurons, and as most of you might know, neurons have axons, what I failed to realize in the beginning of this 6 year escapade, is that those axons in certain areas of the brain, are actually quite long. Take for example the picture of the brain that I have uploaded, the long strands are actually called axonal tracts, theyre long communicative groups of axons from neurons. When the neurons die, the axon dies.

Heres where we lose. When these neurons are replaced with new neurons, the new neurons, do not and can not connect to the same long distance axonal path that was originally there. Rather, the newly generated neurons are primarily bound to attach its axons to the surrounding neurons. Thus not completely repairing the original function of the brain, even if humans could regenerate neurons.

This proof can be seen in this article of the axolotl salamander, in the link posted. Also, dont be confused by the title, neuronal diversity is the main topic of the article, but they elaborate on these long distance axonal tracts not being able to reconnect due to the distance. Its a lot like even if humans could regenerate limbs, if you severed a ligament it would detach from the bone, and even though it could regenerate, or have the ability, it does not have the ability to reach out and reattach itself to the site it was originally attached to. This has to be performed by a surgeon. 

I do beg everyone to read this thoroughly to see if I have made any mistakes in my understanding. Granted I know that some recovery is possible. But its fairly evident our brains will never be the same.

https://elifesciences.org/articles/13998

 

Adult axolotls can regenerate original neuronal diversity in response to brain injury

 

Abstract

The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species.

https://doi.org/10.7554/eLife.13998.001
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eLife digest

Humans and other mammals have a very limited ability to regenerate new neurons in the brain to replace those that have been injured or damaged. In striking contrast, some animals like fish and salamanders are capable of filling in injured brain regions with new neurons. This is a complex task, as the brain is composed of many different types of neurons that are connected to each other in a highly organized manner across both short and long distances.

The extent to which even the most regenerative species can build new brain regions was not known. Understanding any limitations will help to set realistic expectations for the success of potential treatments that aim to replace neurons in mammals.

Amamoto et al. found that the brain of the axolotl, a species of salamander, could selectively regenerate the specific types of neurons that were damaged. This finding suggests that the brain is able to somehow sense which types of neurons are injured. The new neurons were able to mature into functional neurons, but they were limited in their ability to reconnect to their original, distant target neurons.

More research is now needed to investigate how the axolotl brain recognizes which types of neurons have been damaged. It will also be important to understand which cells respond to the injury to give rise to the new neurons that fill the injury site, and to uncover the molecules that are important for governing this regenerative process.

https://doi.org/10.7554/eLife.13998.002

Introduction

Under physiological conditions, the neurogenic capacity of the adult mammalian brain is largely restricted to two neurogenic niches, the subventricular zone of the lateral ventricle, which gives rise to interneurons of the olfactory bulb and the subgranular zone of the dentate gyrus, which generates granule cells of the hippocampus (Ming and Song, 2011). Neurons in other brain regions are only generated during embryonic development and are not replaced postnatally.

In contrast to mammals, other vertebrates are endowed with superior capacity to regenerate multiple organs, including parts of the central nervous system (CNS). Among these, urodele amphibians like the axolotl (Ambystoma mexicanum) are endowed with the capacity to add new neurons to the brain throughout life (Maden et al., 2013) and can regenerate the spinal cord and parts of the brain after mechanical injury (Burr, 1916; Kirsche and Kirsche, 1964a; Butler and Ward, 1967; Piatt, 1955). Resection of the middle one-third of one hemisphere, but not the whole hemisphere, in the axolotl telencephalon results in reconstruction of the injured hemisphere to a similar length as the contralateral, uninjured side (Kirsche and Kirsche, 1964a; Kirsche and Kirsche, 1964b; Winkelmann and Winkelmann, 1970). Similarly, after mechanical excision of the newt optic tectum, new tissue fills the space produced by injury (Okamoto et al., 2007). Interestingly, in the newt, selective chemical ablation of dopaminergic neurons within a largely intact midbrain triggers regeneration of the ablated pool of neurons (Berg et al., 2010; Parish et al., 2007). In addition to urodeles, teleost fish have also been extensively studied for their capacity to regenerate the CNS and have led to the identification of some of the molecular signals involved in the regenerative process (Kizil et al., 2012). These studies highlight the value of regenerative organisms as models to understand the mechanisms that govern brain regeneration for possible application to the mammalian brain.

However, the mammalian CNS is notoriously complex, and its ability to compute high-level functions, like those of the mammalian cerebral cortex, relies on the presence of a great diversity of neuronal subtypes integrated in specific long-distance and local circuits and working within a defined tissue architecture. Disruption of brain structure, connectivity, and neuronal composition is often associated with behavioral deficits, as observed in models of neurodevelopmental, neuropsychiatric, and neurodegenerative disease. It is therefore likely that functional regeneration of higher-order CNS structures will entail the regeneration of a great diversity of neuronal subtypes, the rebuilding of original connectivity, and the synaptic integration of newborn neurons in the pre-existing tissue. It is not known to what extent even regenerative species can accomplish these complex tasks, beyond their broad ability to generate new neurons and to rebuild gross brain morphology. It remains therefore debated whether any vertebrates are capable of true functional brain regeneration.

Using the adult axolotl pallium as the model system, we have investigated whether a diverse array of neuronal subtypes can regenerate and whether their tissue-level organization, connectivity, and functional properties can also regenerate after mechanical injury.

In contrast to the teleostean pallium, the everted nature of which makes linking distinct regions to their mammalian counterparts difficult (Northcutt, 2008), the gross neuroanatomy of the axolotl pallium, organized around two ventricles, shows clear similarities to that of the mammalian telencephalon. In addition, while the evolutionary origin of the mammalian cerebral cortex remains controversial (Molnár, 2011), it is likely that the axolotl pallium contains a basic representation of several of the neuronal subtypes found in the mammalian cerebral cortex and thus may serve as a good model for investigating regeneration of neuronal heterogeneity and complex circuit function.

Here, we demonstrate that both pre- and post-metamorphosis adult axolotls are able to regenerate a diversity of neurons upon localized injury to the dorsal pallium. This process occurs through specific regenerative steps that we defined in live animals using non-invasive magnetic resonance imaging (MRI). Strikingly, newborn neurons can acquire mature electrophysiological properties and respond to local afferent inputs. However, they unexpectedly fail to rebuild long-distance circuit and the original tissue architecture.

The data provide the first proof for the precision with which axolotls regenerate a diverse set of neurons, which in turn become electrophysiologically active and receive local afferent inputs. Notably, however, our results also challenge prior assumptions of functional brain regeneration in salamanders by uncovering unappreciated limitations in the capacity of adult axolotls to fully rebuild original long-distance connectivity and tissue organization, a finding that redefines expectations for brain regeneration in mammals.

axonaltracts.jpg

Edited by dasitmane
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I don't get how you arrived at your conclusion from reading this article. A), we don't know what part of the brain is affected in HPPD. If it's the hippocampus then this articles doesn't really apply because it's well documented to be one of the few areas of the brain where neurogenesis is proven to occur. But again, we don't know this either way. And B), this article doesn't say anything about humans in particular or mention anything about how certain brain regions cannot recover from damage, only that it's not known how many regions are capable of neurogenesis.

Traditional brain science is almost getting turned over on a daily basis. Things that were considered set in stone even a few years ago are frequently up for debate with every passing study. It's well established that different parts of the brain connect and overlap when compromised, so even if HPPD results in cell death in brain areas that aren't well studied there's no need to believe they can't be fully healed. 

The problem with seeing this article as proof that we're out of luck is the simple fact that people who get HPPD do fully recover -- many, in fact. This has been well documented on this site and across the Internet. Though it takes many years for neurogenesis to run its course the countless recovery stories on this site alone are all the proof you need that whatever part of the brain is affected by HPPD clearly has the ability to regrow or reconnect and execute the functions it performed prior to damage. 

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The part of the brain that is effected is any area involving serotonin receptors. Which are very specific neurons that are compromised throughout the entire brain. The damage is very widespread.

This research disregards neurogenesis, so the hippocampus is a mute point.

Yes the axolotl brain is an animal brain, but is still compromised of the same cells, and similar architecture.

The brain may do quite a bit, but it wont fully recover, even with neurogenesis. The study clearly shows that newly made neurons are incapable of reconnecting the long distance axonal growths that previously existed.

Give those who recovered enough coffee and they will realize they haven't recovered. People adapt, people will even lie to themselves that they are fine to get on with their day, day after day. Their neuronal loss maybe wasn't nearly as bad as those who dont "recover". All cases recover to a degree, but massive brain trauma according to what im seeing here can only be repaired to a certain degree and by the laws of nature herself will never repair to 100% functionality. Not from what I can see.

What you're saying is possible, that the brain can reconnect, is exactly what this study shows is not possible. The neurons that are newly generated simply just dont know to send their axons 2mm or more. The brain simply just wont reconnect like it was.

Sorry. I did my best.

Edited by dasitmane
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