Development of muscle atrophy and loss of function in a Gulf-War illness model: underlying mechanisms
Abstract
Gulf War illness (GWI) afflicts military personnel who served during the Persian Gulf War and is notable for cognitive deficits, depression, muscle pain, weakness, intolerance to exercise, and fatigue. Suspect causal agents include the chemicals pyridostigmine (PB), permetrim (PM) and N,N-diethyl-m-toluamide (DEET) used as protectants against insects and nerve gases. No pre-clinical studies have explored the effects on skeletal muscle (SkM). Young male rats were provided PB, PM and DEET at equivalent human doses and physical restraint (to induce stress) for 3 weeks followed a 3-week recovery. GWI gastrocnemius weight was ~ 35% lower versus controls, which correlated with decreases in myofiber area, limb strength, and treadmill time/distance. In GWI rats, SkM fiber type relative abundance changed towards slow type I. Muscle wasting pathway proteins were upregulated while those that promote growth decreased as did mitochondrial endpoints and muscle ATP levels. Proteomic analysis of SkM also documented unique alterations in mitochondrial and metabolic pathways. Thus, exposure to GWI chemicals/stress adversely impacts key metabolic pathways leading to muscle atrophy and loss of function. These changes may account for GWI Veterans symptoms.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 03, 2020
- Source ID
- 10.1038/s41598-020-71486-w
Entities
People
- Aldo Moreno
- Alejandra Garate-Carrillo
- Anaamika Campeau
- David Gonzalez
- Esmeralda Lira-Romero
- Francisco Villarreal
- Guillermo Ceballos
- Israel Ramirez-sanchez
- Javier Estrada-mena
- Maria Loredo
- Marvic Carrillo-terrazas
- Viridiana Navarrete-yañez
Organizations
- Consejo Nacional de Humanidades, Ciencias y Tecnologías
- Foundation for the National Institutes of Health
- National Polytechnic Institute
- United States Department of Defense
- United States Department of Veterans Affairs