Infection and chronic disease activate a systemic brain-muscle signaling axis.
Sci Immunol
; 9(97): eadm7908, 2024 Jul 12.
Article
in En
| MEDLINE
| ID: mdl-38996009
ABSTRACT
Infections and neurodegenerative diseases induce neuroinflammation, but affected individuals often show nonneural symptoms including muscle pain and muscle fatigue. The molecular pathways by which neuroinflammation causes pathologies outside the central nervous system (CNS) are poorly understood. We developed multiple models to investigate the impact of CNS stressors on motor function and found that Escherichia coli infections and SARS-CoV-2 protein expression caused reactive oxygen species (ROS) to accumulate in the brain. ROS induced expression of the cytokine Unpaired 3 (Upd3) in Drosophila and its ortholog, IL-6, in mice. CNS-derived Upd3/IL-6 activated the JAK-STAT pathway in skeletal muscle, which caused muscle mitochondrial dysfunction and impaired motor function. We observed similar phenotypes after expressing toxic amyloid-ß (Aß42) in the CNS. Infection and chronic disease therefore activate a systemic brain-muscle signaling axis in which CNS-derived cytokines bypass the connectome and directly regulate muscle physiology, highlighting IL-6 as a therapeutic target to treat disease-associated muscle dysfunction.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Signal Transduction
/
Muscle, Skeletal
/
COVID-19
Limits:
Animals
/
Humans
Language:
En
Journal:
Sci Immunol
/
Sci. immunol
/
Science immunology
Year:
2024
Document type:
Article