Brain-Muscle Crosstalk in COVID / Alzheimer

Scientists identify a signaling pathway that triggers muscle fatigue in response to nervous system inflammation or infections like SARS-CoV-2.

Originally published by Sneha Khedkar at The Scientist, on Jan 21, 2025

ABOVE: Nervous system infection or inflammation trigger brain-muscle signaling pathways that cause muscle fatigue. ©iStock, Chinnapong

In 2020, as the COVID-19 pandemic escalated, many universities shut down or reduced the capacities of research laboratories in an attempt to limit the spread of the virus. At Washington University School of Medicine in St. Louis, developmental biologist Aaron Johnson was permitted one person in his lab to keep things running. Shuo Yang, then a postdoctoral researcher working on muscle developmental biology, stepped up.

An immunologist by training, Yang, now at Fudan University, was curious to learn more about the virus that was wreaking havoc in the world. Since his model organism—the fruit fly—was not naturally susceptible to the SARS-CoV-2 virus, Yang generated a fly line that expressed a coronavirus protein called open reading frame 3a, or ORF3a, in their brains to mimic infection.1 He observed that this led to motor function impairment; the flies had lost the ability to climb upwards against gravity. 

The researchers noted that this behavior paralleled some general symptoms of illness in humans. “[When] you get sick, your muscles are really tired and achy,” said Johnson. “We’ve all experienced this.” This prompted them to explore the phenomenon in more detail.

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