to Jane---1000questions

[Guest guest]

hello Jane,

It sounds like a wonderful idea to write a book. If you are going to include

some science along with all these wonderful anecdotes from the MSA patients,

though, you need to get some basic understanding of the Nervous System.

A simple book, such as a nurse's Neurology book would help you.

Firstly, the glial cells are not stimulating neurons, i.e. they do not directly

send impulses to other neurons or to muscles. Glial cells are supporting cells

of the nervous system, and there are several types.

Neurons that send impulses do so by way, mostly, of

neurotransmitters---chemicals that cross the space to other neurons or to

muscles. There are many types of neurotransmitters, from the first and well

known, acetylcholine, to norepinephrine to dopamine and to less known smaller

molecules called neuropeptides. Acetylcholine and norepinephrine are the main

neurotransmitters that supply the peripheral striated muscles and smooth

muscles. Dopamine is a neurotransmitter in the brain, among many other

neurotransmitters. It is especially present in the basal ganglia, a part of the

brain that deals with motor function, and dopamine there is what is missing in

Parkinson's Disease.

Messages from the brain get sent through many relay sites to the final

peripheral nerve that stimulates muscle. So malfunction can occur in the brain,

at the relay sites, or at the final neuromuscular junction. This can be caused

by a lack of neurotransmitter, or by a deficit of neuronal capacity.

I'm sure others can answer you specific questions more completely, but I can

address part of them. Some can't be answered at all.

1) There are researchers who are really hot about inclusions and about ASN. Read

their papers, but don't believe everything you read. This may just be a

coincidental finding, as aluminum was in Alzheimer's brains.

2) Cytoplasmic inclusions can not be thought of as tumors because they are in

individual cells and don't make up a mass of cells.

3)I don't think that anyone knows this.

4) Right now there is what I consider an artificial division in types of MSA

based on regions of the brain affected. Since there have been few autopsies to

show that diagnoses based on functional deficits are correct, I believe this to

be yet shown to be a viable division. The MSA web site has information on these

purported types.

5) I don't know.

6) Orthostatic hypotension is caused, as I understand it, because the neurons to

the smooth muscle of the blood vessels do not produce enough norepinephrine to

automatically constrict the vessels, thus not raising the blood pressure to

compensate for standing, as it normally would. In Pure Autonomic Failure it was

thought that the deficit was in the peripheral nerves, yet I have read that in

MSA, the deficit of orthostatic hypotension is in brain control of the autonomic

system (not the same location as the basal ganglia or the cerebellum).

Conflicting ideas.

7.) Ask the experts.

8.) Ibid.

9) The first quote means that synucleins, in very similar forms, are found

throughout the vertebrate kingdom. Their DNA patterns are very similar.

The second quote means they are RELATIVELY abundant in neurons, as opposed to

other cells, like, say, liver cells. And, back to anatomy---the end of a neuron

has special sturctures called presynpatic terminals. Terminals, meaning the ends

of the neurons, and presynaptic, meaning that portion which comes before the

space between the neuron and the next neuron or the muscle. The space is called

the synapse, across which the neurotransmitter chemicals pass.

I hope this has helped some.

Don't be dismayed at the wealth of information that is contradictory, or doesn't

make sense. In research, that is the period in which the most discoveries are

made because there is a big dialogue among researchers, and a sound explanation

comes out eventually.

Barbara J. Woodford, Ph.D., retired neuroanatomist and neuroscientist.

[Jane wrote]

My name is Jane. I wrote to the group already once or twice, a few weeks

ago. I was hired as a caregiver for a man with SDS, three years ago. The

experience had a profound effect on me, and I want to write a book about the

experience, about him, and SDS. I have set aside the next two months to

write, and will see how it goes.

I have been listening to you all for about 6 weeks now, and feel I almost

know some of you. It is a privilege. I have some questions, and surely

more will follow. I hope you won¹t mind my asking. Ask me anything you like

about my background, the tone of the intended book, etcSanything. I have

several goals for this book, but one huge one is to bring attention to MSA,

specifically SDS. I figure attention can¹t help but bring money to

research.

Anyway, right now, I¹m wrestling with exactly what MSA is, how it is caused,

etc. Following, I will write how it all works as I understand it. I¹m

hoping you all can set me straight on the errant parts. Also, I have about

10 questions, and I hope someone (like Bill & Charlotte, the treasure trove

of valuable information!) can help me out.

Thanks a million in advance for any help you can give me. If you feel I am

being intrusive, please tell me, and I¹ll buzz off. I just want to

understand as much as I possibly can about this awful disease, and see what

I can create.

MSA AS I understand it:

In normal brain cell function, the neurons (the glial cells?) creat the

messages for autonomic nerve function. Their messages are sent to the

muscles through nurotransmitters. Dopamine aids in transferring information

by keeping the (neurons? nurotransmitters?) sensitive.

Alpha-synuclein is a protein, (ASN) that normally occurs in our brains. In

MSA, ASN is hyperproduced and forms aggregates that attach themselves to

the neurons (glial cells). Now the message cannot be sent because the glial

cells (GC) lose sensitivity, and the GCs cannot " speak to " the NTs. Or are

they just " speech impaired, " and the message dies on the vine, or are the

messages intermittently sent?

The GCs eventually die.

Sinemet is levodopa plus a catalyst. Levodopa becomes Dopamine in the

brain. It has the ability to go through the blood stream to the brain,

whereas Dopamine cannot.

Dopamine goes to the nurotransmitters to help bring the message across to

the muscles. The less dopamine, the less efficiency.

Whew! Okay, now for the questionsS.

1.) How are the Alpha-synuclein (ASN) inclusions different from Lewy

Bodies?

2.) Could the Glial Cytoplasmic Inclusions be thought of as clumps, or

tumors?

3.) What malfunctions first: the neurons, or the nurotransmitters?

4.) Specifically, what regions of the brain are attacked in SDS? Are they

always the exact same regions or can there be variation?

5.) What symptoms indicate an Autoimmune Dysfunction?

6.) What exactly causes low BP upon rising? (cellular level)

7.) Where should ASN be in the first place?

8.) Is the intended function of ASN known?

9.) What does this mean? " Synucleins are highly conserved proteins in

vertebratesS " ? And this S " especially abundant in neurons and typically

enriched at presynaptic terminals. " ?