Why is the substantia nigra specifically affected in Parkinson's?


#1
The underlying cause of Parkinson’s is the loss of dopamine producing nerve cells in the substantia nigra, a structure of the brain. This raises the question, why aren’t other cells of the body also affected?

We have 30,000 genes (which are made of DNA) in each cell of our body; we may be carrying mutations in one or more of these genes that make us susceptible to a disease. If we compare a skin cell with a nerve cell, both types of cell have the full complement of genes inside them. What is different is that the skin cell has activated a distinct subset of genes (these genes are said to be “expressed”) while the nerve cell expresses a different subset of genes. The action of these different sets of genes imparts the distinctive characteristics of a skin cell and nerve cell. Nerve cell genes are present in skin cells but they have no effect because they are switched off (i.e. they are not expressed). It is the same with skin cell genes in nerve cells. Incidentally, the generation of cloned animals from adult cells is made possible because cells retain all their genes; part of the cloning process is resetting all gene expression back to zero to allow all cell types to develop in the clone. If skin cells had only skin cell genes then cloning a skin cell would end up with a cloned animal made of only skin cells!

Back to the question! Nerve cells naturally express nerve cell genes. If a mutation is present in a skin cell gene (and it disrupts normal function of that gene) it will not affect nerve cells because the gene is switched off in these cells and has no influence; a faulty light bulb has no effect if it remains switched off. The mutation will, of course, affect skin cells. Therefore, the substantia nigra is affected in Parkinson’s disease because mutations are present in nerve cell genes specifically expressed in the substantia nigra.

dr jonny

#2
Saga of the Lost Neurons

Departing from their home in the Substantia Nigra must have been one of the most daunting adventures that our little pals have ever undertaken. Setting out in search of their lost friends and colleagues will prove to be a lengthy and arduous task that will test the most resolute of these tough neurological taxi-drivers. No more short journeys along the N.P.1 (what a car park that is sometimes?)

No more hanging around in the Striatum, hoping for a quick pick up and drop off into Cerebral Cortex for a few dopas. Oh no!!! Out into the big wide world of grotesque reality. No more bopping the night away in that den of inequity called the Reward Centre club, where anything and everything goes. You can delve into every vice that you have ever dreamt of in there! Sex, gambling, booze to name but a few.

Its all there, but only since the newbies arrived. The newbies seem to outnumber us by at least 4 to 1 and there is something not quite right about them. Its like, well, they come across as though they are not real, if you get what I am trying to say. Substitutes is the closest that I can describe. Anyway, they seem that way to me.

Perhaps I am getting a bit paranoid about them. I don’t really know anymore. My memory is not as it was and most of my teeth are rotting or falling out, never mind the fact that I am always skint. Too many excursions into King Levas place I suspect.It never used to be like that. Yeah sure, we would have one or two soirees a year on special occasions, but not every night. Not every god damn night!!!

Actually, come to think about it, King Leva is a newbie too! Its like watching that movie Invasion of the Neuron Snatchers. “Have you seen it? Its quite good I thought, but a bit too far fetched for my liking. Oh well, I had better get back to my watch. I always seem to get the grave yard shift. I wonder why? Gossip has it, that we are moving soon, to a sanctuary called The New Forum. I wonder if all the girls and guys will be back from their quest by then. I certainly hope so, its getting mighty lonesome around here lately!!!

Dopamine neuron 3425657687455 signing off

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Captain Neurons Daily Dairy.

Its been 5 cycles since we all left the Nigra in search of our lost comrades, and we are no nearer to our objective than when we started. We never did have a plan of action or a real target to aim for. But considering all this, my troopers remain positive and eager to renew acquaintance with their misplaced buddies.

We have dispatched out riders in every direction, hoping to gain some insight to their possible whereabouts, but as of yet, nothing has materialised. A couple of my experienced sergeants have taken ill, and I am in a quandary as what to do. They did over indulge at the Reward Centre Club, but we are all guilty of that. I wonder what it could be that’s causing them so much pain?

Our intelligence section captured some Platelets floating around in the plasma, just outside of the Lymph nodes, but we got nothing of note from them for our troubles. We nearly caught some anti-bodies, but they were too big and strong for us to hold on to. Now they would have provided some information. Those guys get just about everywhere at some stage!!! Some of the younger Neurons took a little physical damage during the fray, but it was their pride that took the biggest hit. One of the troopers had a night out with a lovely looking cell from the Pericardium membrane, and it seemed at first that she might have had some first hand knowledge to our comrades position.

But, as in most of these reports, it seems that she mistook our Neurons for some nomadic amino acids. Easily done I suppose!!! We keep bumping into regiments of the recently formed Agonist Division, which all seemed to consist of newbies!!! Very strange that! But, I suppose King Leva knows what he is doing. Who am I to question the Great Leva Dopa? There’s not many of the Old Guard left now!

And to think, they used to call us the Immortals at one time I must make a concerted effort to keep the moral of my troopers as high as possible. They will need it in the coming weeks. Where did they go? Why did they go? These are questions that I must get answers to, if we are to find the missing Neurons I am still a little confused and also surprised why King Leva, let all of us go on this mission so readily? In fact, it was with his blessing and he insisted that as many of the Old Guard set out as possible. I of course left a trusted battalion to over see all these newbies. I had to.

They are so carefree and reckless that things would soon deteriorate into utter chaos. It reminds me somewhat of those dark cycles of long ago when we were invaded by the purple heart cells or LCD’ers as we used to call them. Now that was some story, that was! If we are not careful, even those events could be surpassed.
Sergeant of the NeuroGuard, please call the troops to attention for Dopamine inspection!!!!!!

Captain Neuron 5464 signing off

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A letter to my Neural Receptors back home in S.N. City

Why are we here? That’s what I want to know.All we get off the high ups is bullshit!
Those neurons that went over the wall are long gone or brown bread! We’ve heard talk of bad goings on, and guess whose behind it all? Yep, you got it in one!

The Great Leva Dopa Neuron.They reckon that he’s knocking us off in our millions, and replacing us all with those ******* newbies. The Bastards!!! Why is he doing it?
I knew when those fake fuckers turned up that they weren’t the real McCoy. Like robots they are. Until they get in the old Reward club, that is! Watch em go then, its like watching insulin let loose on the blood sugars. Whiz, pop, wham bam, thank you ma’am!

Im scared of whats gonna happen to all of us. None of these cells like us down here, because they think we are posh and should **** off back to the brain where we belong. And most of us agree with em. A couple of the sarges are playing up and pretending to be sick, just to maybe influence the skipper into turning back home. I don’t think its going to work though. Ive seen the skip in this mood before and when his mind is made up, its made up!! He will probably send em back as soon as we come across an artery. Express delivery, so to speak.

Going by capilliary is so slow, especially if those fat cholesterol buggers are hanging about. Have you ever stood next to them? Leva!!! Its awful! The stench is terrible. They should be scraped out and burnt. They would burn easy for 5 cycles, no problem!

Guess what I did last cycle? You’ll never guess in 10,000 cycles. I chatted up a lovely heart cell. Well, shes not exactly in the heart, but she works on the outskirts of it. Do you know it? Its called the Pericardium. I thought my luck had changed when I met her, especially as I haven’t had you know what for countless cycles.

Turns out that shes Asexual, and does it all on her own. No wonder they are all short sighted around here!!! She wouldnt like it if one of those huge white corpuscles caught hold of her! She even mistook me for an amino acid dude. I ask you? Hold on. Whats that? THAT’S JUST GREAT AT THIS TIME OF CYCLE. The sarge has just called a Dopa inspection. Ah well, back to the old gall stone

Dopamine Neuron 1st class 34256754654 signing off

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Report of Inspection.
Sergeant of the fighting 5th Neuroguard Regiment

Instructed by Captain Neuron to undertake a Dopamine Inspection on all members of the 5th Battalion on the 28th cycle of Leva calendar. 1,650 troopers including 8 sergeants, 16 corporals and 16 lance-corps and 10 medics. Only a bare handful of troopers and none of the N.C.O.s are producing their full capacity of Dopamine.
Most of us are down to below the 20% mark, with no signs of improvement. Fatigue and anxiety is gripping the majority of the Regiment, and that’s after double rations of dried Mucuna leaves were distributed.

The medics have suggested a programme of D.D.S. while we are on our travels, to help combat the immobility problem that a lot of the troopers are complaining of at the moment Deep dendrite stimulation will give them a quick fix until we return to the Substantia Nigra. And only the Captain knows when that will happen.

WHAT THE DEVIL IS THAT COMMOTION???? LANCE CORPORAL!!!!

What the hell is going on out there? Who is blowing that darned bugle?
Sarge!! We are under attack by a large detachment of anti-bodies!!!!

Our under par Dopa count must be registering us as alien cells for this lot to send in so many. There’s dozens of ‘em! And I think a couple are from their special branch.
You know, them ones with the super enlarged tendrils. Get the sappers to lay down some Leva-dopa cluster bombs around our perimeter. The L-Dopa signature from them beauts are just like the real thing. If it can dupe the AB’s into believing that we are ok and don’t need eradicating, we should be fine. Jump to it, Lance!!!

Right Lance! Get the troops into formation with the Old Guard at the apex of each diamond, but make sure they are tight, real tight. We’ll give those hairy string anti-bodies something to think about!!!!

I WONDER WHATEVER HAPPENED TO THOSE NEURONS?.

#3
Love it Pokermid, very, very clever. X