Development of muscle atrophy and loss of function in a Gulf-War illness model: underlying mechanisms.
Development of muscle atrophy and loss of function in a Gulf-War illness model: underlying mechanisms.
复制标题
海湾战争疾病模型中肌肉萎缩和功能丧失的发展：潜在机制。
DOI：
10.1038/s41598-020-71486-w
复制
发表时间：
2020
影响因子：
4.6
通讯作者：
Villarrea
中科院分区：
文献类型：
--
作者：
Ramirez-Sanchez,Israel;Navarrete-Yañez,Viridiana;Garate-Carrillo,Alejandra;Loredo,Maria;Lira-Romero,Esmeralda;Estrada-Mena,Javier;Campeau,Anaamika;Gonzalez,David;Carrillo-Terrazas,Marvic;Moreno-Ulloa,Aldo;Ceballos,Guillermo;Villarrea
海湾战争疾病(GWI)困扰着在波斯湾战争期间服役的军事人员，其显著特征是认知缺陷、抑郁、肌肉疼痛、虚弱、运动不耐受和疲劳。可疑的致病因素包括用作昆虫和神经毒气保护剂的化学物质吡斯替格明(PB)、安定(PM)和N，N-二乙基-间甲苯胺(DEET)。目前尚无临床前研究探讨其对骨骼肌(SKM)的影响。幼年雄性大鼠在恢复3周后，给予相当于人的剂量的PB、PM和DEET，并给予身体束缚(以诱导应激)3周。GWI组的腓肠肌重量比对照组降低~ 35%，这与肌纤维面积、肢体力量和跑台时间/距离的减少有关。在GWI大鼠中，SKM纤维型的相对丰度向慢型I型转变，肌肉损耗途径蛋白上调，而促进生长的蛋白减少，线粒体终点和肌肉ATP水平下降。对SKM的蛋白质组学分析还记录了线粒体和代谢途径的独特变化。因此，暴露于GWI化学物质/应激对导致肌肉萎缩和功能丧失的关键代谢途径产生不利影响。这些变化可能解释了GWI退伍军人的症状。
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.