Infection and chronic disease activate a systemic brain-muscle signaling axis - Published July 12, 2
Jul 14, 2024 23:01:55 GMT
Post by Nadica (She/Her) on Jul 14, 2024 23:01:55 GMT
Infection and chronic disease activate a systemic brain-muscle signaling axis - Published July 12, 2024
Editor’s summary
Neuroinflammation can cause symptoms outside of the central nervous system (CNS), including muscle pain and fatigue, yet how inflammatory signals in the brain are communicated to muscle remains to be determined. Using multiple models of CNS stress in fruit flies, Yang et al. identified that reactive oxygen species accumulation in the brain promoted expression of Upd3, a Drosophila ortholog of interleukin-6 (IL-6). IL-6 activated JAK-STAT signaling in skeletal muscle, resulting in mitochondrial dysfunction–impaired motor function. This axis was also activated in mice after CNS stress and evident in humans with neuroinflammation. This work identifies a conserved brain-to-muscle signaling axis that regulates muscle performance, which may be a promising therapeutic target. —Hannah Isles
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-β (Aβ42) 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.
Editor’s summary
Neuroinflammation can cause symptoms outside of the central nervous system (CNS), including muscle pain and fatigue, yet how inflammatory signals in the brain are communicated to muscle remains to be determined. Using multiple models of CNS stress in fruit flies, Yang et al. identified that reactive oxygen species accumulation in the brain promoted expression of Upd3, a Drosophila ortholog of interleukin-6 (IL-6). IL-6 activated JAK-STAT signaling in skeletal muscle, resulting in mitochondrial dysfunction–impaired motor function. This axis was also activated in mice after CNS stress and evident in humans with neuroinflammation. This work identifies a conserved brain-to-muscle signaling axis that regulates muscle performance, which may be a promising therapeutic target. —Hannah Isles
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-β (Aβ42) 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.