PPS: Confronting Fatigue
Eddie Bollenbach

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Eddie Bollenbach Bio & Picture

Edward P. Bollenbach
Professor Emeritus in Microbiology and Chemistry

Date: Wed, 30 Dec 1998 15:25:42 -0500
From: "Eddie Bollenbach"
Subject: Confronting Fatigue!

"You will find that fatigue has a larger share in the promotion and transmission of disease than any other single condition you can name."
-- Sir James Paget 1814-1899, Dictionary of Scientific Quotations

Interesting quote. Clearly we are not alone and there has been a very recent development in this area. A team led by Kazuo Inoue of the Graduate School of Agriculture at Kyoto University, Japan, has been exploring the phenomenon of fatigue. His group put rats into a tub from which they could not escape and allowed them to swim to exhaustion. When this happens their bodies produce a variety of chemicals that communicate with the brain. The brain, then, generates a substance called Transforming Growth Factor-beta (TGF-beta). This chemical is believed, among other effects, to promote growth activity.

Abstract Of Study - Physiol Behav 1998 May;64(2):185-90

Inoue's group, then, drew some of the cerebrospinal fluid from the exhausted rats. It had a lot of TGF-beta in it. They also drew fluid from control rats that were not exercised or exhausted. They injected the spinal fluid from the exhausted rats directly into mice, at a CSF-filled space behind the cerebellum called the cisterna magna. They did the same to another group of mice but used the fluid control without TGF-beta in it. The mice that got the TGF-beta decreased their motor activity up to 75% when compared with the control mice. They became FATIGUED. We polio survivors, undoubtedly, are sending chemical signals to the brain all the time because of our overworked muscles. We also know, according to Inoue, that humans produce TGF-beta too.

Here is the kicker: the group produced an antibody against TGF-beta. When they injected it into exhausted mice the mice perked right up and recovered from the fatigue. It would be interesting to see if drugs could be developed to interact with TGF-beta in humans, or if biotechnology could mass produce an antibody. It would also be interesting to see if we could parse the categories of fatigue we all talk about eg. localized, general, brain, and so on and better understand their relationship to one another. Inoue's work has the potential to broaden our understanding enormously. This is a significant development in understanding the genesis of fatigue in my judgement.

"According to Inoue, TGF-beta is a primary candidate for modulating spontaneous motor activity in the brain". It should be possible to produce antibodies against the human form and have a direct antidote to our fatigue, assuming the chemical plays the same role in humans as it does in mice. We are about 90% similar genetically so its a good bet. We'll have to wait and see. The only thing for sure is that it will undoubtedly be expensive.

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