Infection and chronic disease activate a brain-muscle signaling axis that regulates muscle performance.
Shuo YangMeijie TianYulong DaiShengyong FengYunyun WangDeepak ChhanganiTiffany OuWenle LiZe YangJennifer McAdowDiego E Rincon-LimasXin YinWanbo TaiGong ChengAaron N JohnsonPublished in: bioRxiv : the preprint server for biology (2022)
Infections and neurodegenerative diseases induce neuroinflammation, but affected individuals often show a number of non-neural symptoms including muscle pain and muscle fatigue. The molecular pathways by which neuroinflammation causes pathologies outside the central nervous system (CNS) are poorly understood, so we developed three models to investigate the impact of neuroinflammation on muscle performance. We found that bacterial infection, COVID-like viral infection, and expression of a neurotoxic protein associated with Alzheimer′ s disease promoted the accumulation of reactive oxygen species (ROS) in the brain. Excessive ROS induces the expression of the cytokine Unpaired 3 (Upd3) in insects, or its orthologue IL-6 in mammals, and CNS-derived Upd3/IL-6 activates the JAK/Stat pathway in skeletal muscle. In response to JAK/Stat signaling, mitochondrial function is impaired and muscle performance is reduced. Our work uncovers a brain-muscle signaling axis in which infections and chronic diseases induce cytokine-dependent changes in muscle performance, suggesting IL-6 could be a therapeutic target to treat muscle weakness caused by neuroinflammation.
Keyphrases
- skeletal muscle
- reactive oxygen species
- traumatic brain injury
- poor prognosis
- cerebral ischemia
- insulin resistance
- coronavirus disease
- dna damage
- sars cov
- cell death
- blood brain barrier
- lps induced
- white matter
- depressive symptoms
- physical activity
- brain injury
- resting state
- oxidative stress
- long non coding rna
- binding protein
- metabolic syndrome
- spinal cord
- pain management
- neuropathic pain
- inflammatory response
- respiratory syndrome coronavirus
- protein protein
- single molecule