Parkinson's Disease Tulip


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Old 04-11-2011, 09:21 PM #1
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Default Dopamine and regeneration

Check this article on dopamine and neuronal regeneration. I really don't know what to think about the sentence that says, well, you read it for yourselves and comment, here's the link:

http://www.barchester.com/Healthcare...nt%3F/376/4306
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Old 04-12-2011, 04:27 AM #2
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Default ...it comes as no suprise to me

....the more you read on the forums and the more scientific papers you see....

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Old 04-12-2011, 04:50 AM #3
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Default More alarmed by the implications

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Originally Posted by krugen68 View Post
....the more you read on the forums and the more scientific papers you see....

Lurking,

I see several weird things going on here. First why salamanders? Salamanders are known for regrowing their own tails, maybe in finding out how that is accomplished and can humans do something similar? That might be helpful. I don't know if they are the best model for the human brain. They have found upon autopsy that even advanced pwp had newer neuronal growth.

Next, the whole Sinemet as toxic to us thing has been hotly debated for decades. It is true that our bodies learn to make less of a substance that is being supplied for it, but I don't think we would permanently lose that ability. People here have lowered their meds after years of high doses and with DBS so I think it is really odd for them to suggest that we suffer without l-dopa in order to "recover " later. How and when exactly does this "recovery then take place?

Furthermore, if dopamine signaling is blocked, the salamander generates even more unneeded dopa? This is potentially bad news for schizophrenic people who rely on dopa receptor blockade to control their symptoms. How does this apply to us? The dopa is needed. Once again it seems to say we should not take agonists in order produce more l-dopa?

Finally, it is clear that the researchers are a bit "off". They did not induce PD in a salamander...does a salamander who has lost 80% of its dopa able to supercharge and regenerate enough dopamine to recover that profound a loss all in one day or does it take weeks? Maybe giving l-dopa to a salamander who has all its own dopa intact results in overpoduction of ldopa and toxicity, and it stops making its own as a way to maintain homeostasis?

Something is very off with this article. It wants to say that any sort of dopaminergic treatment (even agonists) is harmful. Well what alternative do we have? They do not offer one that i can see. Maybe we will one day have GABA and adenosine receptor agonists as our gold cadillac treatment but for now we're stuck and frankly I'd rather be able to move than to worry about whether or not I can begin to generate my own dopamine 10 or 20 years from now.

It looks like it may have been translated from Polish, so I am hoping for researchers sake there is a translation issue otherwise..... Am i the only one finding this "news" rather dubious? Even if we did leave sinemet alone our brains will never naturally regain their full functioning on its own anyway so what is their point?

Laura
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Old 04-12-2011, 07:25 AM #4
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The Karolinska Institute is a heavy weight Swedish medical research center. I don't know about the relevance of salamanders, but it makes sense that there would be little incentive to regenerate neurons if you were being flooded with sinemet. The solution might be as simple as titration.
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Born in 1953, 1st symptoms and misdiagnosed as essential tremor in 1992. Dx with PD in 2000.
Currently (2011) taking 200/50 Sinemet CR 8 times a day + 10/100 Sinemet 3 times a day. Functional 90% of waking day but fragile. Failure at exercise but still trying. Constantly experimenting. Beta blocker and ACE inhibitor at present. Currently (01/2013) taking ldopa/carbadopa 200/50 CR six times a day + 10/100 form 3 times daily. Functional 90% of day. Update 04/2013: L/C 200/50 8x; Beta Blocker; ACE Inhib; Ginger; Turmeric; Creatine; Magnesium; Potassium. Doing well.
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Old 04-12-2011, 08:23 AM #5
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Default former posting

http://neurotalk.psychcentral.com/thread148186.html

seems salamanders recover from PD symptoms and thus far is the only animal model that does that I have read about. early in the process of PD care, one MDS noted that the primary problem in PD research was that there was not a good animal model. do not know if salamanders would be one. madelyn
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Old 04-12-2011, 08:56 AM #6
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Default Brings up an interesting question....

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Originally Posted by olsen View Post
http://neurotalk.psychcentral.com/thread148186.html

seems salamanders recover from PD symptoms and thus far is the only animal model that does that I have read about. early in the process of PD care, one MDS noted that the primary problem in PD research was that there was not a good animal model. do not know if salamanders would be one. madelyn
Madelyn,

It's true there is no really good animal model. Further, I remember learning that my cousin's dog came down with Addison's disease, and we know pets get cancer or can be epileptic. Animals can have an essential tremor, but I have yet to hear of them developing PD? If environment is a player wouldn't it be resulting in PD in them as well. Even when they induce lab animals for PD research there is no degenerative process that takes hold, I think, or may be someone knows differently.

I didn't mean to come down so hard, I just don't get where the therapeutics come in. I'll have to see if I can find the original article. I think the write up of the study is ambiguous.
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Old 04-12-2011, 09:52 AM #7
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Default cell stem cell

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Originally Posted by Conductor71 View Post
Madelyn,

It's true there is no really good animal model. Further, I remember learning that my cousin's dog came down with Addison's disease, and we know pets get cancer or can be epileptic. Animals can have an essential tremor, but I have yet to hear of them developing PD? If environment is a player wouldn't it be resulting in PD in them as well. Even when they induce lab animals for PD research there is no degenerative process that takes hold, I think, or may be someone knows differently.

I didn't mean to come down so hard, I just don't get where the therapeutics come in. I'll have to see if I can find the original article. I think the write up of the study is ambiguous.

*
http://www.cell.com/cell-stem-cell/r...3459091100052X
I believe this is a link to the published study


from the study itself... this is the summary written by the authors of the study

Summary

Appropriate termination of regenerative processes is critical for producing the correct number of cells in tissues. Here we provide evidence for an end-product inhibition of dopamine neuron regeneration that is mediated by dopamine. Ablation of midbrain dopamine neurons leads to complete regeneration in salamanders. Regeneration involves extensive neurogenesis and requires activation of quiescent ependymoglia cells, which express dopamine receptors. Pharmacological compensation for dopamine loss by L-dopa inhibits ependymoglia proliferation and regeneration in a dopamine receptor-signaling-dependent manner, specifically after ablation of dopamine neurons. Systemic administration of the dopamine receptor antagonist haloperidol alone causes ependymoglia proliferation and the appearance of excessive number of neurons. Our data show that stem cell quiescence is under dopamine control and provide a model for termination once normal homeostasis is restored. The findings establish a role for dopamine in the reversible suppression of neurogenesis in the midbrain and have implications for regenerative strategies in Parkinson's disease.
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Old 04-12-2011, 10:06 AM #8
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Cool

Quote:
Originally Posted by Conductor71 View Post
Lurking,

I see several weird things going on here. First why salamanders? Salamanders are known for regrowing their own tails, maybe in finding out how that is accomplished and can humans do something similar? That might be helpful. I don't know if they are the best model for the human brain. They have found upon autopsy that even advanced pwp had newer neuronal growth.

Next, the whole Sinemet as toxic to us thing has been hotly debated for decades. It is true that our bodies learn to make less of a substance that is being supplied for it, but I don't think we would permanently lose that ability. People here have lowered their meds after years of high doses and with DBS so I think it is really odd for them to suggest that we suffer without l-dopa in order to "recover " later. How and when exactly does this "recovery then take place?

Furthermore, if dopamine signaling is blocked, the salamander generates even more unneeded dopa? This is potentially bad news for schizophrenic people who rely on dopa receptor blockade to control their symptoms. How does this apply to us? The dopa is needed. Once again it seems to say we should not take agonists in order produce more l-dopa?

Finally, it is clear that the researchers are a bit "off". They did not induce PD in a salamander...does a salamander who has lost 80% of its dopa able to supercharge and regenerate enough dopamine to recover that profound a loss all in one day or does it take weeks? Maybe giving l-dopa to a salamander who has all its own dopa intact results in overpoduction of ldopa and toxicity, and it stops making its own as a way to maintain homeostasis?

Something is very off with this article. It wants to say that any sort of dopaminergic treatment (even agonists) is harmful. Well what alternative do we have? They do not offer one that i can see. Maybe we will one day have GABA and adenosine receptor agonists as our gold cadillac treatment but for now we're stuck and frankly I'd rather be able to move than to worry about whether or not I can begin to generate my own dopamine 10 or 20 years from now.

It looks like it may have been translated from Polish, so I am hoping for researchers sake there is a translation issue otherwise..... Am i the only one finding this "news" rather dubious? Even if we did leave sinemet alone our brains will never naturally regain their full functioning on its own anyway so what is their point?

Laura
It seems to me that the article was an attempt to cut and paste several articles together without adequate knowledge. There are 3 separate and unrelated themes two of which I recognize from totally unrelated studies and a possible 3rd nonsequitir.

1. The salamander stuff and levodopa is interesting and informative until:
2. The statement about "the converse being true"...nothing was done in that particular study to "block" dopamine receptors so it must refer to the mysterious 3rd study.
3. The 2nd study recognized was done on Utah genealogy databases looking at 2.2M records since 1904 and has nothing to do with dopamine. People who had PD listed under "causes of death" had their medical genealogy tracked.

It's just a bad article.
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Old 04-12-2011, 10:57 AM #9
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Default article

ahhh, slow news day.
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The future is already here — it's just not very evenly distributed. William Gibson
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Old 04-12-2011, 11:01 AM #10
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Default .....research outside the box gets my vote.....

""Something is very off with this article. It wants to say that any sort of dopaminergic treatment (even agonists) is harmful. Well what alternative do we have? They do not offer one that i can see. Maybe we will one day have GABA and adenosine receptor agonists as our gold cadillac treatment but for now we're stuck and frankly I'd rather be able to move than to worry about whether or not I can begin to generate my own dopamine 10 or 20 years from now. ""

I totally accept your point about wishing to move now, HOWEVER unless we encourage challenging research activity outside the dopamine / DA mindset, Pharma and reactionary parts of the medical community will be happy to feed coming generations the same hackneyed palliatives for the next 40 years.
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Last edited by krugen68; 04-12-2011 at 11:03 AM. Reason: punctuation
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