Given our weird stress vulnerability, I wonder just what the metabolic priority is when NE is needed. That is, since dopamine is used as raw material to make NE and the stress response involves production of both NE and epinephrine, if there is not enough DA to go around, what comes first. From an evolutionary standpoint I would assume that the two adrenal products would allow me to escape more mastodons and the DA would be sacrificed.

If that is so, then our stress response may be burning up our DA or at least using up the tyrosine that we need to make both.

Finally, you ever notice that the very things we need to make our own DA are verboten if we take sinemet. Protein and Vitamin B6 in particular?

And as long as I am being paranoid, a possible explanation for why there is so little research on this might be the nature of the research that WAS conducted on it in the 70s - depression. It was seen as a possible rival for the new SSRIs. Couldn't have that, now, could we?

Isn't there a connection between stress and inflammation? And if so, why has no one done any research on the effects of cortisone (the greatest anti-inflammatory ever!) on PD? Or am I missing something?

Yes, indeed on the connection! Anne Frobert, the French MD and PWP who drops in occasionally, and I got into that quite deeply. Want to know something funny? PD is not a disease of the nervous system. It is the combined disorders of the endocrine (stress), immune (inflammation), and GI (toxins) systems doing damage to the nervous system. A subtle distinction, at least until you try to reallocate the research funding!

There is more depth at http://www.parkinsonsonline.org/PD_Outline_Index.html but, briefly, if we are exposed to bacterial toxins in the womb at just the right time, then we are born with extra sensitivity to further exposure. Since that particular toxin is everywhere, the inevitable result is inflammation. How much depends on our individual sensitivity (one reason that not everyone gets PD).

At the same time a similar sensitizing of our stress response can take place through exposure to maternal stress hormones. Our controls get set wrong.

Both these vulnerabilities last into childhood and even past puberty because areas of our brain remain "plastic" until then. We did a poll on the old BT of twenty of us and, as a general rule, we had all been through hell as children in one form or another.

So, in a nutshell, we go through life with inflammation releasing cytokines, neuron damaging chemicals. The body responds by releasing anti-inflammatory cortisol, another neuron damaging chemical. Meanwhile, stress releases more cortisol AND also triggers more inflammation. <I swear I don't know how endocrinologists stay sane.>

Inflammation leads to leaky gut and also leaky BBB. Toxins seep out of the GI tract and end up in the brain. The sensitized immune cells there go ape and neurons die in the crossfire.

Now, that is a ten cent explanation of a dollar subject (as you will see if you follow that link to the outline) but the bottom line by the time we end up here is inflammation and stress. We can't just throw corticoids at it because that adds to the damage. We have to take a broader, dare I say "wholistic", approach.

Destress our lives - the earlier the better.
Reduce cortisol with things like gingko and ginseng.
Reduce inflammation with things like curcumin.
Calm down the little warriors in the brain with things like green tea.
Take care of ourselves the same way that we took care of others all our lives.

Hmm...what was the question?

When a chemist makes potential sSRI's, the biologists always check out at least the in-vitro receptor binding Nor-Epi mimetic properties, and now , some nor-epi component to potential SSRI's is considered either a good thing or at least inconsequential (unless it's just too potent).
You posed a thoughtful question about out evolutionary intention re; adrenergics derived from the tyrosine-l-dopa pool. I thought about it and concluded that dopa is sacrificed during fight or flight responses, but, getting ramped up on to much of the "Go" sympathomimetics wouldn't really serve us well during our often extensive periods when we were not in any threat. This would give the dopa pool rime to recharge, and the dopamine pump used accordingly as "a brake" to the cholinergic system. I am a wiki-head, so here are a couple of 4-leafed clover's that you might have looked over. Basically they are the first page and other "clickably" ( "clickably", a new cyber-word?) retrieved pages from the parent.

http://en.wikipedia.org/wiki/Adrenaline_junkie

http://en.wikipedia.org/wiki/Epinephrine

basically, if you are the kind who would be inclined, click EVERYTHING on the parent page. One can learn a lot about our central nervous system regulation here. It always has amazed me how fast biochemical reactions can be. Nature has produced some fascinatingly fast enzymatic transformations. Did you know that dopa is very quickly transformed and utilized when it gets to where it is metabolized; in most cases only hanging around for a minute or two!!!

Thanks cs. I am the type and have been clicking merrily for the last hour.
Along the way I came across this:
http://www.acnp.org/default.aspx?Pag...rationChapters
Although slightly dated (2000) this is one heck of a work and the individual chapters are downloadable. It is a massive (2000 pgs) tome from the American College of Neuropharmacology and even has a section on PD that is ahead of the curve even now. Enjoy.

This is getting near the area that I, at least, think is the heart of PD, namely the interactions between damaged endocrine (stress) and immune (inflammation) systems and their effects on the nervous system. I noticed that stress and the related chemistry can interfere with the uptake and use of trptophan, BTW. Perhaps another piece of the puzzle.

I'm going to bravely just jump in a little on this - I forget what wonderful person said this but I totally loved it - I've got PD not a PhD -

Some traditional Chinese interpretations of the origins of PD centered on the stomach and gut, challenging the idea of the brain as the king organ, but what Rick says in that case "feeds" (sorry) right into that idea.

And about the stress and maternal stress - I can totally relate. I have always felt that the manifestation in me of PD was larger than just me, and had something to do with intergenerational stress - my mother as a deported war laborer surviving the fall of Berlin in World War II, my greatgrandmother losing 8 sons, a husband and a father during another war, my mother moving me from England to the US when I was five because she was so afraid of the Cold War and thought we might be safer there - how could all of that not have informed their bodies and my body in formation and then development? It makes sense.

They call it "epigenetics" because their throat closes up if they admit it.

If a pregnant rat is put under a high stress load at a critical time, her pups will react differently than they would have. In plain language, they'll be high-strung.

But the really interesting part is that, even if the little fellows are kept in total stress free luxury, her grandpups are also affected. Now, to me, that is a startling finding. Think what happens if the pups are kept in a high stress situation and the grandpups too. They would become increasingly higher strung unless they could adapt. If the stress comes and goes, then adaptation might not even be possible. So, you would have a gradual increase in stress related problems in the population. Each generation would be a little worse off. The weak, the old, would be the first to show it. But as the stress induced weakness affected younger and younger people so would the "diseases" that went with it.

And that's why, I think, that PD was born in the Industrial Revolution.

In
http://www.dcnutrition.com/AminoAcid...cordNumber=129
it states that tyrosine can be used as an adjunct in the treatment of PD.
it says metabolism of tyrosine necessitates large doses compared to L-Dopa. Also, its effectiveness is increased when combined with Sinemet.
This may be why I did not see much improvement of symptoms when I tried it some years ago. I did not take it together with Sinemet, and did not know high doses are needed due to its fast metabolism.
I read somewhere that tyrosine can not be sythesised in the brain, which is presumably why the above paper describes it as a nutriant.
It is synthesised in the body and readily passes the BBB to be made into L-dopa, dopamine and adrenalin.
Ron

that the conversion of tyrosine to dopa by the enzyme tyrosine hydroxylase in the cns occurs in healthy, live neurons, the very thing in short supply in us parkies. Supplementing with extra tyrosine may provide some help early on, but will be increasingly limited by the decreased number of working dopaminergic neurons. (I think I just stated the obvious!)

bump bump bump