13 replies to this topic

[pi-]

I've been looking through Regulatory mechanisms underlying the differential growth of dendrites and axons

 

The main gist is that certain molecules enhance neurite growth, others block it, and there is a second pair of categories that stimulate dendrite growth while restricting axon growth or vice versa. These are called differential regulators.

 

I'm very surprised that although I have spent weeks digging into the subject, practically everything in this paper seems new. Previously I learned that VPA/Ibuprofen interrupt the RhoA/ROCK signalling chain that inhibits the axon (and dendrite?) growthcone.

 

In the above paper, Sema3A is mentioned: "Sema3A promotes dendritic growth but restricts axonal growth..."

 

And it turns out RhoA activates Sema3A (Local translation of RhoA regulates growth cone collapse)

 

Ok, good, one connection has been made!

 

However, I'm currently experiencing information overload -- to demonstrate, here are my currently open browser tabs:

   
Rac1 and RhoA Promote Neurite Outgrowth through Formation and Stabilization of Growth Cone Point Contacts

 

(2004) Abl Tyrosine Kinase Promotes Dendrogenesis by Inducing Actin Cytoskeletal Rearrangements in Cooperation with Rho Family Small GTPases in Hippocampal Neurons

 

(2014) Proteomic identification of the molecular basis of mammalian CNS growth cones <-- this one contains the most intricately detailed diagram of the growthcone I have ever seen

 

(2014) Collapsin response-mediator protein 5 (CRMP5) phosphorylation at threonine 516 regulates neurite outgrowth inhibition

 

that last one is interesting, it talks about CRMP2 stimulates dendrite growth, CRMP5 inhibits CRMP2 from functioning.  So scanning pubmed for CRMP2 gives a few hits as well (below)

 

(2014) Regulatory mechanisms underlying the differential growth of dendrites and axons <-- differential regulators.  "Recent studies have uncovered two distinct types of regulatory mechanisms that differentiate dendritic and axonal growth: dedicated mechanisms and bimodal mechanisms. Dedicated mechanisms regulate either dendritespecific or axon-specific growth; in contrast, bimodal mechanisms direct dendritic and axonal development in opposite manners."

 

Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation

 

Evidence for the Role of MAP1B in Axon Formation

 

CRMP2 pubmed hits:

CRMP2: Functional Roles in Neural Development and Therapeutic Potential in Neurological Diseases

 

Amelioration of β-amyloid-induced cognitive dysfunction and hippocampal axon degeneration by curcumin is associated with suppression of CRMP-2 hyperphosphorylation

 

Identification of a dithiol-disulfide switch in collapsin response mediator protein 2 (CRMP2) that is toggled in a model of neuronal differentiation

 

CNP/cGMP signaling regulates axon branching and growth by modulating microtubule polymerization

 

Localized role of CRMP1 and CRMP2 in neurite outgrowth and growth cone steering

 

Preconditioning with Ginkgo biloba (EGb 761®) provides neuroprotection through HO1 and CRMP2

 

- - - - - - -- - - - - - -- - - - - - -- - - - - - -- - - - - - -- - - - - - -- - - - - - -

 

It would be really helpful to have some kind of a roadmap here, some giant chart showing how everything connects. I've never heard of such a thing -- I wonder if it even exists.

 

A few of those papers near the end mention known noots like Curcumin, Gingko. It would be very nice to be able to place  existing drugs/noots on such a chart.

 

Finally, the picture I am getting (mainly from that first paper) is that there are a number of different regulators, and the brain is able to use this to design different regions in different ways. For example, the part dedicated to focusing the eyes on an object can be finalised and etched within a few months, whereas the part dedicated to 3D sound localisation must be kept plastic throughout life (different air temperature means different spatial cues).

 

I'm hoping that gradually I will start to make sense of all this information; if anyone else is interested in this jigsaw, please do contribute!

 

π

[middpanther88]

How interesting! A chart would be a boon!

[Flex]

I actually screwed arround with "millions of opened browser-tabs at the same time" in the past Years -.-

I will try to contribute, if I dont forget it.

 

Edited by Flex, 07 September 2014 - 03:25 AM.

[pi-]

2013 -- Potentiation of neuritogenic activity of medicinal mushrooms in rat pheochromocytoma cells

 

^ this paper contains a useful image showing two signalling pathways that activate neurite growth.

 

 

AARGHHH!!! How do I embed the image? FFS! :(

 

I cannot upload it.  If I use the 'Image' icon it requires a web location for the image. Which is http://www.ncbi.nlm....82-13-157-5.jpg

 

but then it says "this type of image format is not accepted on this forum".

 

What the HELL? Since when is a jpeg not the most common format for images on the Internet?

 

So I convert it to a .PNG, upload it using pasteboard.co (http://pasteboard.co/4J0w7RM.png)

 

Now no error, but it looks like that failed also.

 

Grr. Ok I guess I'll have to use attachments in the future.

Attached Files

•  shrooms.png   104.03KB   3 downloads

[sylvan-k]

Have you run across any research about acetyl-l-carnitine arginate? I remember reading something about how it enhanced neurite growth.

[Flex]

Nice one

[sylvan-k]

Wish I could find my notes. :(

 

Everything I'm finding now is parroted by some outfit selling the stuff.

 

Great work, BTW Pi.

[Flex]

IIRC it increases the ammount of NGF receptors, whereas Acetyl-carnitine acts as an agonist and increases the sensitivity of the receptor to 100x

 

[sylvan-k]

As I recall, acetyl carnitine increased growth by 5% or so over 5 days, the arginated version bumped that up to 25%.

 

I mix that with lions mane to enhance growth even more.

 

It may not be as crazy as some of the other things people are playing with, but the substances are super safe.

 

Sorry, I don't mean to hijack with a discussion of supposed supplements that increase neurite growth. This seems more of a discussion about the underlying mechanisms.

[pi-]

Actually I'm looking for the various supplements out there.  What I do is for each one figure out what signalling pathways it activates. I'm keeping quiet at the moment as I'm still learning the various pathways, and it is slow going. I am compiling my research on a localhost Wiki, which I will make public at some point in the future.

 

So far I've found several types of mushroom have been shown to promote neurite growth, also Ashwangadha.

 

But bear in mind, the adult body is constantly secreting a bunch of messagers that activate SEMA3A pathway which prevents axon growth cones from forming (it is one of those bimodal regulators I was talking about in the original post, I originally called them differential regulators which wasn't right, they are bimodal regulators).  So unless you're knocking out SEMA3A, I would not expect too much.

 

Strittmatter has developed a small molecule that does this, but it is an early stages of FDA testing out I can't see any way to source it, unless a group of us club together and get the molecule synthesised separately (the molecule is available in the patent document).

 

Ibuprofen does the job, but you need to maintain a high-dose level, 2400mg/day, which is going to cause inflammation of the stomach lining / gastric ulcers. Maybe just about doable if supplemented with something that prevents the stomach from producing too much acid like omeprazole. But definitely not the ideal tool for the job.

 

π

[normalizing]

2013 -- Potentiation of neuritogenic activity of medicinal mushrooms in rat pheochromocytoma cells

 

^ this paper contains a useful image showing two signalling pathways that activate neurite growth.

 

 

AARGHHH!!! How do I embed the image? FFS! :(

 

I cannot upload it.  If I use the 'Image' icon it requires a web location for the image. Which is http://www.ncbi.nlm....82-13-157-5.jpg

 

but then it says "this type of image format is not accepted on this forum".

 

What the HELL? Since when is a jpeg not the most common format for images on the Internet?

 

So I convert it to a .PNG, upload it using pasteboard.co (http://pasteboard.co/4J0w7RM.png)

 

Now no error, but it looks like that failed also.

 

Grr. Ok I guess I'll have to use attachments in the future.

 

 

results based on animal studies are generally not reliable much but what you posted is completely off being in vitro.

 

why dont you guys concentrate on NO in vitro studies, SOME animal studies and PREDOMINANTLY human studies...

 

[pi-]

@Normalizing, how come you have -17 underneath your avatar despite nearly 400 posts? Could it possibly be related to the content?

 

@middpanther88, the best set of signalling charts I have found are here: http://www.qiagen.co...athway central/

 

Edited by pi-, 18 September 2014 - 02:32 PM.

[normalizing]

pi- i was dissagreeing alot with popularly accepted ideas on topics. try it yourself if you like as an experiment, argue against popular belief and see how well you do. of course i must highlight this, i didnt do it intentionally, i actually believe most of the shit out there thats popularly accepted and believed is wrong! therefore, ill say something even if costs me!

[PWAIN]

Normalizing, it probably not so much what you say as how you say it. People are not so bothered if someone has differing views, more that they perceive the post appearing to come from someone who presents like an arrogant prick. That probably isn't true but if you often present in such a way then what else are they to think? The sad thing is that much of what you say may be valid but it gets dismissed because of this. I'm not saying any of the above to offend you or for that matter calling you an arrogant prick,I'm just trying to help you see that you are losing impact because of something as simple as presentation. I reckon what you have to say is worth more.

Edited by PWAIN, 20 September 2014 - 12:31 AM.