Brain inflammation may cause decreased muscle function, leading to fatigue, according to a new study.

Researchers at Washington University School of Medicine wanted to understand how brain inflammation affects muscles.

They found that proteins released from the inflamed brain reduce energy levels in skeletal muscle, leading to fatigue and decreased muscle function.

This research, published in the journal Science Immunology, was conducted on fruit flies and mice.

It identified ways to block this process, raising new hope for treating muscle pain and fatigue in diseases such as Alzheimer’s and long Covid.

According to the study, inflammation in the brain or neuroinflammation is caused by infections, long-term diseases like Alzheimer’s, and normal aging, which impairs nerve function by altering neuron structures.

Although it mainly affects the central nervous system (CNS), it also causes muscle problems.

“It’s not just because we don’t feel well, it’s because we lack motivation to move,” said Dr. Aaron Johnson, senior author of the study.

“These processes reduce energy levels in skeletal muscle, which decreases the ability to move and function normally,” he said.

The study modeled three types of diseases, E. coli bacterial infection, SARS-CoV-2 viral infection, and Alzheimer’s, to determine how CNS stressors affect motor function.

They found that inflammatory proteins in the brain cause the accumulation of reactive oxygen species, which activate the production of interleukin-6 (IL-6) in mice.

This results in activation of the JAK-STAT pathway in muscle, leading to mitochondrial dysfunction and impaired motor function.

Experiments showed that flies and mice that had COVID-related proteins in their brains had reduced motor function.

Flies with these proteins did not climb as well, and mice did not run as well. Similar effects were seen with bacterial proteins and the Alzheimer’s protein amyloid beta.

“We also found evidence that this effect may be long-term,” Johnson said. “Even if the infection resolves quickly, the reduced muscle performance in our experiments persisted for several days.”

The researchers believe these findings are likely relevant to humans as well.

For example, inflammation-causing SARS-CoV-2 proteins have been found in the brains of COVID-19 patients during autopsies, and many long-term COVID patients report extreme fatigue and muscle weakness long after the initial infection has ended.

The discovery that the JAK-STAT pathway in muscle reduces mitochondrial energy production points to a potential treatment for muscle weakness related to brain inflammation.

However, it is still unclear why the brain sends signals that harm muscle function when exposed to these diseases.

The researchers speculate that this may be a way for the brain to reallocate resources during illness, but they stressed that more research is needed.