By studying flies and mice, researchers have found a way to stop muscle weakness linked to common illnesses such as bacterial infections or long covid.
- The researchers wanted to understand why very deep muscle fatigue was associated with certain diseases such as long covid, bacterial infections or even neurodegenerative pathologies.
- They found that brain messenger proteins linked to inflammation travel through the bloodstream and reduce energy levels in skeletal muscles.
- They also identified potential targets to prevent or treat muscle weakness linked to brain inflammation.
Many infections or neurodegenerative diseases are accompanied by muscle weakness or significant muscle fatigue. By studying fruit flies and mice, a team from the Washington University School of Medicine in St. Louis (USA) has shed light on the mechanism behind this disorder. Brain inflammation, caused by these common diseases, releases a specific protein that travels from the brain to the muscles and leads to a loss of muscle function.
The study is published on July 12, 2024 in the journal Science Immunology.
Infection: Brain messenger proteins cause muscle weakness
To study the effects of brain inflammation on muscle function, the researchers modeled three types of pathology: a bacterial infection with E. coli, a viral infection caused by SARS-CoV-2, and Alzheimer’s disease. They studied their effects in mice and fruit flies.
They found that when the brain is exposed to the inflammatory proteins that are characteristic of these diseases, harmful chemicals build up in the organ. Called reactive oxygen species, they cause brain cells to produce an immune molecule called interleukin-6 (IL-6). IL-6 travels throughout the body through the bloodstream. The team found that IL-6 in mice—and the corresponding protein in fruit flies—reduced energy production in muscle mitochondria.
“Flies and mice that had COVID-19-associated proteins in their brains showed reduced motor function: the flies didn’t climb as well as they should have, and the rodents didn’t run as well or as much as the control group.”explains lead author Aaron Johnson in a communicated of his establishment.
“We observed similar effects on muscle function when the brain was exposed to proteins associated with bacteria and the Alzheimer’s disease protein amyloid beta. We also find that this effect can become chronic. Even if an infection is rapidly cleared, reduced muscle performance persists for several days longer in our experiments.”adds the expert.
In their press release, the scientists specify that the same mechanisms are probably present in humans. “Bacterial meningitis of the brain is known to increase IL-6 levels and may be associated with muscle problems in some patients, for example. Among COVID-19 patients, SARS-CoV-2 inflammatory proteins have been found in the brain at autopsy, and many long-Covid patients report extreme fatigue and muscle weakness, even long after the initial infection has cleared. People with Alzheimer’s disease also have increased IL-6 levels in the blood as well as muscle weakness.”
Muscle fatigue linked to infections: a possible treatment avenue identified
This study managed to identify targets that open the door to potential treatments. The researchers discovered that IL-6 activates what is called the pathway signaling JAK-STAT in muscle. Linked to the cellular regulation, it leads to a reduction in the energy production of mitochondria. Several drugs, for example, against arthritis, already on the market, are known to block this pathway.
The team believes that it would be interesting to conduct further clinical research to better understand the mechanisms involved and determine whether existing treatments can help patients suffering from muscle fatigue linked to infections or inflammatory diseases.
