Date: Sun, 16 Jul 2000 20:31:27 -0400
From: "Eddie Bollenbach" <edward.bollenbach @ snet.net>
Subject: [PPM] Comments (somewhat technical)
Memory and subjective feelings of deep "central" fatigue certainly have a cause. A woman just wrote of her husband whose mental state, including memory, improved with mestinon. Mestinon is a cholinesterase inhibitor and primarily effects voluntary muscle nerve transmission, although there are some other neurons which communicate using acetyl choline. I guess my point is if a drug has a positive effect on the body to reduce muscle/nerve fatigue the results can be seen in every system, including mental systems. There are many cellular hormones (cytokines) which communicate between soma and psyche. We know this but we have not identified all of them and their functions.
This is why I am very wary about claims that people with profound motor unit damage have specific mental effects which are not directly linked to the known motor unit damage of polio. Claims are made in studies about low levels of dopamine and other neuropeptides, which are under-secreted because of polio brain damage. This may be so but the brain has more substitution and repair mechanisms than we ever knew. Certainly more than motor neurons in the cord or periphery do. One example of brain adaptation is when dopamine secretion is low. The brain area that requires it as a ligand produces more dopamine receptors in response. And It is not just receptors that can grow. New brain cells can too.
There is even a new idea that cell growth occurs inside the hippocampus of normal brains regularly and that the new cells grow and interconnect there all the time. Glucocorticoids, caused by stress, inhibit this growth. People who have depression all of their lives have a significantly smaller hippocampus because the cell growth is absent or low during depression. This is why in some of the brain imaging studies of post-polio people it is essential to screen out those who have or have had depression if you want to show what is polio related. I think this is a very hard thing to do.
Serotonin, another neurotransmitter, increases cell growth in this hippocampal area. There is a recent suggestion that the reason it takes antidepressants 3 to 6 weeks to work is because it takes this long for the effect of new cell division to be realized in the brain. Certainly the serotonin should appear much more quickly, as a result of the drugs, if depression were simply caused by a low serotonin level.
Back to polio. If you ascribe low dopamine for an answer to a symptom you have to show brain microanatomy to prove it. By the way, this would not be hard to show after the death of a polio survivor. Dopamine agonists or dopamine itself can be labeled in a variety of ways and introduced into the brain area of study. If that area "lights up" we'll know its loaded with receptors. Microscopic studies can show how many dopamine secreting cells are intact. It seems pretty elaborate to me to measure dopamine by prolactin when prolactin waxes and wanes depending on body position, time of day, stress, light exposure, physical activity, and who knows what else. However, I will reserve further comment on the paper recently mentioned on this list until after I have had time to read and study it.
I've always felt we should apply Occam's razor before blindly
accepting elaborate mechanisms to describe symptoms. If dopamine is
low in the brain it should affect all 5 dopamine receptor categories
and their subsets of receptors, and also the chain of effector neurons
and their ultimate processes. Finally, I always need more than the
prescribed medicine to feel better, especially since PPS laid me low,
but I'm six one and still taller than some short people, even in my
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