Activity, Motor Control & Coordination
Pain - Thermal Allodynia / Hyperalgesia
Pain - Spontaneous Pain - Postural Deficit
Pain - Mechanical Allodynia / Hyperalgesia
Anxiety & Depression Disorder
Learning/Memory - Attention - Addiction
Physiology & Respiratory Research
Metabolism - Food & Drink Intake
Pain
Metabolism
Motor control
Neurodegeneration
Cross-disciplinary subjects
Muscular system
General activity
Mood Disorders
Other disorders
Joints
Central Nervous System (CNS)
Sensory system
Authors
JH Lee, SW Kim, JH Kim et al
Lab
Gwangju Institute of Science and Technology, Republic of Korea
Journal
Research Square
Abstract
Inflammation-mediated skeletal muscle wasting is induced by inflammatory cytokines. It occurs in critically ill patients with sepsis (termed intensive care unit acquired weakness) and patients with advanced metastasis (termed cancer cachexia). Both conditions severely impact on patient morbidity and mortality. Lithium chloride has been investigated as a drug repurposing candidate for numerous diseases. In this study, we assessed whether lithium chloride affects inflammation-mediated muscle wasting, using in vitro and in vivo models of cancer cachexia and sepsis. Lithium chloride prevented wasting in myotubes cultured with cancer cell conditioned media, maintained expression of the muscle fiber contractile protein, myosin heavy chain 2 and blocked upregulation of the E3 ubiquitin ligase, Atrogin-1. Glycogen synthase kinase-3beta inhibition was indicated as the target mechanism, due to the following observations: 1) beta-catenin was upregulated in the myotubes and 2) inhibition of IMPA1, the secondary biological target of lithium chloride, did not inhibit the effects of cancer conditioned media. Lithium chloride inhibited upregulation of the inflammation-associated cytokines Il-1beta, Il-6 and inos in macrophages treated with lipopolysaccharide. Lithium chloride treatment in an animal model of sepsis improved body weight, increased muscle mass, preserved the survival of larger fibers and decreased expression of the wasting effector genes, Atrogin-1 and Murf-1. In a model of cancer cachexia, lithium chloride increased muscle mass, enhanced muscle strength and increased fiber cross sectional area, with no significant effect on tumorigenesis. These results indicate that lithium chloride could be repurposed as a drug to treat patients with inflammation-mediated skeletal muscle wasting.
BIOSEB Instruments Used:
Grip strength test (BIO-GS3)
