Gulf War Illness (GWI) is defined by the Centers for Disease Control and Prevention (CDC) as a multi-symptom illness having at least one symptom from two of three factors, which include: fatigue, mood-cognition problems, and musculoskeletal disorders. The cluster of long-term symptoms is unique to military personnel from coalition countries including United States, Australia, and the United Kingdom that served in Operation Desert Storm from 1990 to 1991. Reporting of these symptoms is much lower among soldiers deployed in other parts of the world like Bosnia during the same time period. The exact cause of GWI is unknown, but combined exposure to N,N-diethyl-m-toluamide (DEET), organophosphates like chlorpyrifos (CPF), and pyridostigmine bromide (PB), has been hypothesized as a potential mechanism. Mitochondrial dysfunction is known to occur in most neurodegenerative diseases that share symptoms with GWI and has therefore been implicated in GWI. Although exposure to these and other toxicants continues to be investigated as potential causes of GWI, their combined impact on mitochondrial physiology remains unknown. In this study, the effects of combined GWI toxicant exposure on mitochondrial function were determined in a commonly used and readily available immortalized cell line (N2a), whose higher rate of oxygen consumption resembles that of highly metabolic neurons in vivo. We report that combined exposure containing pesticide CPF 71 μM, insect repellants DEET 78 μM, and antitoxins PB 19 μM, causes profound mitochondrial dysfunction after a 4-h incubation resulting in decreased mitochondrial respiratory states in the absence of proapoptotic signaling, proton leak, or significant increase in reactive oxygen species production.

中文翻译：

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溴化吡啶斯的明、毒死蜱和避蚊胺联合海湾战争暴露损伤抑制神经母细胞瘤细胞的线粒体功能

海湾战争病 (GWI) 被美国疾病控制与预防中心 (CDC) 定义为一种多症状疾病，至少具有来自三个因素中的两个的一种症状，其中包括：疲劳、情绪认知问题和肌肉骨骼疾病。这组长期症状是 1990 年至 1991 年间参与沙漠风暴行动的美国、澳大利亚和英国等联军国家的军事人员所独有的。部署在其他地区的士兵中报告这些症状的比例要低得多。与同一时期的波斯尼亚一样的世界。GWI 的确切原因尚不清楚，但联合暴露于N,N-二乙基间甲苯酰胺 (DEET)、毒死蜱 (CPF) 等有机磷酸酯和溴化吡斯的明 (PB) 被认为是一种潜在机制。已知线粒体功能障碍发生在大多数与 GWI 有共同症状的神经退行性疾病中，因此与 GWI 有关。尽管接触这些和其他毒物作为 GWI 的潜在原因仍在研究中，但它们对线粒体生理学的综合影响仍然未知。在这项研究中，在常用且容易获得的永生化细胞系 (N2a) 中确定了组合 GWI 毒物暴露对线粒体功能的影响，该细胞系的较高耗氧率类似于体内高代谢神经元的耗氧率。我们报告称，含有杀虫剂 CPF 71 μM、驱虫剂 DEET 78 μM 和抗毒素 PB 19 μM 的组合暴露，在 4 小时孵育后会导致严重的线粒体功能障碍，导致在缺乏促凋亡信号、质子泄漏或活性氧产生显着增加。