Development of muscle atrophy and loss of function in a Gulf-War illness model: underlying mechanisms

Ramírez-Sánchez, Israel; Navarrete-Yañez, Viridiana; Garate-Carrillo, Alejandra; Loredo Mendoza, María Lilia; Lira, Esmeralda; Campeau, Anaamika; Estrada Mena, Francisco Javier; González, David; Carrillo-Terrazas, Marvic; Moreno-Ulloa, Aldo; Guillermo Ceballos; Villarreal, Francisco J.

doi:10.1038/s41598-020-71486-w

Development of muscle atrophy and loss of function in a Gulf-War illness model: underlying mechanisms

Journal

Scientific Reports

ISSN

2045-2322

Date Issued

2020

Author(s)

Ramírez-Sánchez, Israel

Navarrete-Yañez, Viridiana

Garate-Carrillo, Alejandra

Loredo Mendoza, María Lilia

Facultad de Ciencias de la Salud - CampCM

Lira, Esmeralda

Facultad de Ciencias de la Salud - CampCM

Campeau, Anaamika

Estrada Mena, Francisco Javier

Facultad de Ciencias de la Salud - CampCM

González, David

Carrillo-Terrazas, Marvic

Moreno-Ulloa, Aldo

Guillermo Ceballos

Villarreal, Francisco J.

Type

text::journal::journal article

DOI

10.1038/s41598-020-71486-w

URL

https://scripta.up.edu.mx/handle/20.500.12552/2130

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.