Why autoimmune?

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Postby notasperfectasyou » Sun Feb 01, 2009 9:21 pm

Actually there are other models. I can't find them right now, but I know I've read papers that use something involving something like copper sulfate, or something that sounds like that but with more syllables. I know that I've read a paper about MS models somewhere too. Can't put my finger on them right now though. Ken
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Postby Lyon » Sun Feb 01, 2009 9:49 pm

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Last edited by Lyon on Sat Nov 26, 2011 9:05 pm, edited 1 time in total.
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Postby Terry » Sun Feb 01, 2009 10:13 pm

I thought that gathering opinions and evidence that only counter the autoimmune hypothesis, without necessarily presenting some other cause for MS, could be useful.


Here is one for you, Sou.



If MS is an autoimmune disease a particularly informative setting for studying this would be in patients who have MS and are concomitantly infected with HIV infection, a situation which is known to induce a severe state of immune deficiency. Berger et al. reported seven such patients, six of whom developed an immunodeficient state after HIV infection but who continued to have relapsing-remitting MS....These data would
argue strongly against any autoimmune aetiology, i.e.T-cell mediated autoimmune pathogenesis. (Behan et al. 2002)
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Postby CureOrBust » Mon Feb 02, 2009 2:21 am

notasperfectasyou wrote:that use something involving something like copper sulfate, or something that sounds like that but with more syllables
I am guessing you meant this one?
http://www3.interscience.wiley.com/journal/119385971/abstract?CRETRY=1&SRETRY=0
The cuprizone model is a model for toxic demyelination. In this model, young mice are fed with the copper chelator cuprizone, leading to oligodendrocyte death and a subsequent reversible demyelination. Spontaneous remyelination can be seen as early as 4 days after withdrawal of cuprizone.


Lyon wrote:Interesting Ken. I looked all over heck and find assorted variants of the EAE model, but ......they are all variants of EAE?? :roll:
http://www.ajnr.org/cgi/content/full/28/1/190
The most common experimental models for multiple sclerosis can be described as immune-mediated or virus-induced, and these distinctions form the basis for the organization of the book into 4 sections. The first and longest section covers "Experimental Allergic (Autoimmune) Encephalomyelitis (EAE)." In these 576 pages and 27 chapters, EAE is given a comprehensive treatment, including history, histopathology, genetics, roles of individual cell types and processes, and a single section devoted to EAE in primates. The second section devotes 119 pages and 9 chapters to "Theiler’s Murine Encephalomyelitis Virus (TMEV)–Induced Demyelination." The 139 pages and 13 chapters of the third section cover "Corona Virus–Induced Demyelination," and the final shorter section has 1 chapter each on "Semliki Forest Virus-Induced Demyelination" and canine distemper virus–induced demyelination.

Is EAE Virus induced?

and there are ones like this one also.
http://www3.interscience.wiley.com/journal/109696968/abstract
Demyelination in a transgenic mouse: A model for multiple sclerosis
Abstract
A transgenic mouse containing 70 copies (ND4) of the transgene encoding DM20, a myelin proteolipid protein, appeared clinically normal up to 3 months of age. By 8-10 months, it showed tremors, unsteady gait, and dies shortly thereafter. We concluded that the clinical symptoms correlated with demyelination based on the following criteria: (1) at 10 months of age only 17% of the amount of myelin obtained from normal mice was isolated from the ND4 mice; (2) astrogliosis, a prominent feature of demyelinating disease was minimal at 3 months of age but prominent by 10 months; (3) at the electron microscopic level disrupted myelin was seen at 8 months of age in the ND4 mice and ingested myelin debris was found in astrocytes; (4) lymphocytic infiltration in association with endothelial cells was observed routinely in the ND4 mice; (5) sections through optic nerves showed denuded and thinly myelinated axons in the 8 month old ND4 mice.
Although the mechanism by which demyelination takes place is not fully understood, measurements of the amounts of PLP suggest it is down-regulated by the large amount of DM20. Since DM20 is a major proteolipid in the young but a minor one in the adult, the persistence of high levels in the adult results in improperly assembled myelin which is prone to disruption. Therefore demyelination in the ND4 mouse appears to result from the persistence of immature myelin into the adult. © 1993 Wiley-Liss, Inc.
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Postby Lyon » Mon Feb 02, 2009 7:14 am

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Last edited by Lyon on Sat Nov 26, 2011 9:04 pm, edited 1 time in total.
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Postby notasperfectasyou » Mon Feb 02, 2009 7:56 am

I got the copper part right, that's gotta be worth at least a double yoi!
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Postby CureOrBust » Mon Feb 02, 2009 3:43 pm

Lyon wrote:You aren't hinting that I'm fallible are you?
Not at all, I thought EAE was induced auto-reactivity to myelin, but i don't know if it was virus induced(and still don't?); and hence it would actually give some substantiation to your statement that they were all EAE variants. The quote I supplied appears to group EAE in with the other virus induced demylinating models. I was just too lazy/uninterested to do the search for myself.
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Postby notasperfectasyou » Wed Mar 04, 2009 9:00 am

Here's a model I had never seen before

JHM strain of mouse hepatitis virus (JHMV)
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Postby mrhodes40 » Wed Mar 04, 2009 9:26 am

Wow I did not hear of hepatitis mouse either. that's a germ again though

There is also Theilers Murine encephalomyelitis. It is a strain of mice that have been given an intestinal virus that causes mouse demyelination in a way that causes a relapsing disease similar to ms. A virus.

THe thing that strikes me about that is that the genuine autoimmune mouse disease EAE is a self limiting disease, it ends and clears up eventually, just like rheumatic fever does in people (which we know is autoimmune-we know what the antigenic target is, something we have never found in MS).

BUT this theilers thing, a VIRAL disease mimics MS. If the mouse doesn't clear it from the brain then it is chronic like MS.

the mice are manipulated genetically by knocking out or otherwise changing their genes related to immune fucntion to not clear the virus because otherwise it would go away on its own in wild type mice. Mice with different genetic "problems" have varying severity of disease.

But the totally wierd thing is that even though we are assuming MS is autoimmiune this is created using a virus it is supposed to mimic MS because it is relapsing, once again creating a model based on what we think, not on what is real about MS. But since its a virus doesn't that beg the question about why we assume MS is autoimmune?

Here's one about why EAE has nothing to do with MS on a cellular/cytokine level. No wonder these findings never help us!
http://www.direct-ms.org/pdf/Immunology ... ritque.pdf


Hmmmmmmm.............
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Postby patientx » Wed Mar 04, 2009 3:43 pm

Marie,

I had never heard of Theilers Murine encephalomyelitis, until your last post. I've started going to Google university to read up on it, and it is fascinating. Am I the only person with MS who had never heard of this? (And I have heard of EAE, and how poor of a model it is.)

I've only started reading about this, but one article I came across is this:

http://www.jimmunol.org/cgi/content/abs ... 61/10/5586

The date of this article is 1998. Why hasn't more been done with this model in the last 10 years?
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Postby mrhodes40 » Wed Mar 04, 2009 4:35 pm

PX, I see what you mean about that. Yes I wonder why more research is not done on Theiler's as well. It is pretty interesting, makes you wonde rif it is harder to cure than EAE :roll:

I've only known about theiler's for about a year so not everyone knos about theiler's mouse. Never heard of the hepatitis one either!
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Postby furch » Thu Mar 05, 2009 5:16 pm

interesting discussion, im wondering, does the issue of autoimmune or not neccesarly have to relate to MS in particular? i mean, with borrelia/lyme the exact same mechanisms take place, and it wouldnt be unreasonalble to think that other bacteria aquired from other sources than tick-bites can cause the same or similar havoc in the brain or other areas..? When researchers research MS, the do it under the premise of MS - thus focusing on a very narrow starting-point perhaps? im thinking the accumulated data from any other "autoimmune disease" is valuable, even if its complex and too numerous to comprehend..?

I found this paper to be very interesting regarding this, it sort of elevates the platou of perspective a bit, Check it out:

http://autoimmunityresearch.org/transcr ... genome.pdf

i'd really like to hear youre thoughts on it:)
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