Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Induced by Repeated Forced Swimming in Mice, 2019, Hara et al

Andy

Andy

Retired committee member
More rodent torture. They may well have established chronic fatigue through over-training the mice but they haven't proven this as a mouse model for ME/CFS.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by disabling fatigue of at least 6 months, in addition to symptoms such as muscle pain and muscle weakness. There is no treatment provides long-term benefits to most patients. Recently, clinical research suggested the involvement of pyruvate dehydrogenase (PDH) in ME/CFS. PDH is a crucial enzyme in the mitochondria matrix that links glycolysis to the tricarboxylic acid cycle and oxidative phosphorylation. However, it is little known whether PDH could be a therapeutic target.

The purpose of this study was to establish ME/CFS in mice and to investigate the involvement of PDH in ME/CFS. To induce the chronic fatigue in mice, a repeated forced swimming test was conducted. To evaluate fatigue, we measured immobility time in forced swimming test and starting time of grooming. An open field test was conducted on day 8. After 25 d of the forced swimming test, the mitochondrial fraction in gastrocnemius muscle was isolated and PDH activity was measured. Moreover, we evaluated the effect of PDH activation by administering sodium dichloroacetate (DCA). In ME/CFS mice group, the immobility time and starting time of grooming increased time-dependently. In addition, the moved distance was decreased in ME/CFS mice. PDH activity was decreased in the mitochondrial fraction of the gastrocnemius muscle of the forced swimming group. DCA treatment may be beneficial in preventing fatigue-like behavior in ME/CFS. These findings indicate that ME/CFS model was established in mice and that a decrease in mitochondrial PDH activity is involved with the symptom of ME/CFS.
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Open access at https://www.jstage.jst.go.jp/article/bpb/42/7/42_b19-00009/_html/-char/en
 
Using a similar approach they could probably produce results that indicate that speed is a cure for torture induced fatigue in mice, or that it at least has a 'beneficial' effect on mouse PTSD.

I wonder at what point it will occur to them that injecting hydrochloric acid into mice is a way of getting them to move faster, or that vivisection produces frantic activity and then has a 'calming' effect.

Some people seem to have significant issues with mice.

I can't wait for the cute fluffy kitten research to start.:banghead::banghead::banghead:
 
This trying to produce a mouse model for ME/CFS is just ludicrous.
You need to know what the disease is first.
So you have in another study them forcing the mice to stay in cages semi-submerged in water and in this one forcing them to swim.
Name me one ME patient who developed ME either way.

also mice can spend hours running around in a wheel............
 
They quote Fluge and Mella who, in this paper, showed reduced PDH in ME blood cells:
Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight, 1, e89376 (2016).

And they quote the Comhaire paper of a small pilot open label study using DCA which we discussed here.
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It seems this study is showing that overexercise in mice produces reduced PDH, reduced activity and increased fatigue, and DCA partially reverses these.

It also seems that that ME in humans involves reduced PDH, reduced activity and increased fatigue, and DCA may partially reverse these.

What that doesn't prove, is that exercise induced fatigue in mice is the same as what is happening in ME. But I think it's an interesting finding that could reflect part of the picture of ME.

Since many of us with ME started or got worse by pushing through and exercising at a 'normal' level when we were sick, perhaps this has the same effect as overexercise, and triggers low PDH. Why though, would that become permanent in ME even when we are not exercising?

It would have been interesting if they had another group who were followed up for a few weeks after the overexercising regime to see if their activity, fatigue and PDH returned to normal once they were allowed to rest as much as they needed to.
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Note also from the conclusion of the mouse paper:
''However, previous reports demonstrated that treatment with DCA caused adverse effects with oxidative stress in hepatic tissues, hepatomegaly, and decreased the locomotor activity.''
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That makes exactly as much sense as claiming to have a Parkinson's mouse model by subjecting mice to cold and therefore have them shaking uncontrollably. And for good measure, it's equally cruel.

Superficial similarities are a specific problem of classification and no expert should be confused about the need to be careful about mixing issues sharing those.

The birth of modern science began with efforts to classify and distinguish things that are different from one another and why. This is legitimately a medieval mistake as far as the scientific method goes.
 
I first started reading research articles on ME/CFS back in 2009 or so, and one of the first ones I came across was a series of similar experiments with rats being forced to swim. I look forward to the next logical steps, forcing fish to walk, elephants to fly, and CFS psychiatrists to think.
 
This is all the wrong way round anyway. What is lacking is basic research into the normal biology of cells and energy production. If the complete biochemistry was known it would be much easier to see what is going wrong with us.

That research could be done on planarian worms or fruitflies.
 
alex3619 said:
Exactly.
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It's probably more accurate to say they provoked acute fatigue.

Which is a perfect example of how confused medicine tends to be about this critical difference. 3 inches of rain in 24 is a problem. 1/2 inch of daily rain is one hell of a more serious problem, even if in absolute numbers it may seem superficially less problematic, it absolutely isn't.

I really badly want to make experiments with medical professionals and make them experience chronic pain. With consent, of course, this can be provoked with natural compounds that cause no physical injury but nonetheless leave long-term severe pain. It's absurd that something this basic has to be experienced to be believed but apparently it's required. If they're confident that chronic symptoms are completely different and a trivial issue that you can simply happy-think your way out, then prove it MF.

No one in their right mind would do it and yet they keep insisting that anyone can do it and if you don't then you're a failure. What a load of crap.
 
Trish said:
Since many of us with ME started or got worse by pushing through and exercising at a 'normal' level when we were sick, perhaps this has the same effect as overexercise, and triggers low PDH. Why though, would that become permanent in ME even when we are not exercising?
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One of the potentially stupid things I did in the wake of the severe upper respiratory infection I had (which began about three weeks before onset) was to resume my practice going for long bike rides in the evening, which typically left me drenched in sweat. I only did this once or twice during the week after I felt I had fully recovered. It wasn't the only stupid thing I did in the wake of that "flu." I also was exposed to a lot of fumes while painting a room with little ventilation.

I've wondered if one route to ME could be the disruption of the "recovery sequence" following a bad infection. We tend to think of the return to normal following a "flu" as simply turning down the dial on the immune response to zero, but maybe there is some sequence that needs to be followed and, if it's disrupted during recovery, perhaps the sequence can get "stuck," or turn into something worse than "stuck."

Just a thought that's crossed my mind over the years...


[If you were going to try to simulate this in mice, it seems like the mice would need to be recovering from "mouse flu," whatever that is, before you stressed them.]
 
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