Infections and neurodegenerative diseases cause inflammation of the brain. However, for unknown reasons, patients with brain inflammation often have muscle problems that appear to be unrelated to the central nervous system.
A recent study revealed how encephalitis releases a specific protein that travels from the brain to the muscles and causes loss of muscle function.
Deep muscle fatigue associated with some diseases
The study, conducted by researchers at Washington University School of Medicine in St. Louis and published July 12 in the Journal of Immunology, was conducted in fruit flies and mice and also identified ways to block the process, which could have implications for treating or preventing muscle wasting sometimes associated with inflammatory diseases, including bacterial infections, Alzheimer’s disease and long COVID.
According to the EurekAlert website, lead researcher Aaron Johnson, an associate professor at Washington University School of Medicine in St. Louis, says: “We are interested in understanding the deep muscle fatigue associated with some common diseases.”
“Our study suggests that when we become ill, proteins sent from the brain travel through the bloodstream and reduce energy levels in skeletal muscles,” he added. “This is more than just a lack of motivation to move because we don’t feel well. These processes reduce energy levels in skeletal muscles, reducing the ability to move and function normally.”
To investigate the effects of brain inflammation on muscle function, the researchers used three different types of diseases: E. coli infection, SARS-CoV-2 (COVID-19) viral infection, and Alzheimer’s disease.
harmful proteins
When the brain is exposed to inflammatory proteins characteristic of these diseases, harmful chemicals known as reactive oxygen species build up. The reactive oxygen species cause brain cells to produce an immune molecule called interleukin-6, which travels throughout the body in the bloodstream.
Researchers found that interleukin-6 in mice and its corresponding protein in fruit flies reduce energy production in muscle mitochondria, the power plants in cells.
“Mice and fruit flies that had COVID-associated proteins in their brains showed decreased motor function,” Johnson said. “The fruit flies didn’t climb as well, and the mice didn’t run as well or as much as the control mice that didn’t have the disease.”
“We saw similar effects on muscle function when the brain was exposed to bacteria-associated proteins and Alzheimer’s amyloid beta proteins,” he added. “We also see evidence that this effect can become chronic, with even if the infection is cleared quickly, reduced muscle performance persisting for days longer in our experiments.”
Johnson, along with University of Florida researchers and senior author Dr. Shuo Yang—who did the work as a postdoctoral researcher in Johnson’s lab—argue that the same processes are likely relevant in humans. Bacterial meningitis is known to increase levels of interleukin-6 and may be linked to muscle problems in some patients.
Similar condition in Covid-19 patients
Among COVID-19 patients, SARS-CoV-2 inflammatory proteins have been found in the brain during autopsies, and a number of long COVID patients have reported severe fatigue and muscle weakness long after the initial infection has cleared. Alzheimer’s patients have also shown elevated levels of interleukin-6 in the blood as well as muscle weakness.
The study identified potential targets for preventing or treating muscle weakness associated with encephalitis. The researchers found that interleukin-6 activates what’s called the JAKST pathway in muscle, which causes reduced energy production in mitochondria. There are several FDA-approved treatments for other diseases that can block this pathway.