Acute gene expression changes in the mouse hippocampus following a combined Gulf War toxicant exposure.
Acute gene expression changes in the mouse hippocampus following a combined Gulf War toxicant exposure.
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DOI：
10.1016/j.lfs.2021.119845
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发表时间：
2021-11-01
期刊：
影响因子：
6.1
通讯作者：
Citron BA
中科院分区：
文献类型：
--
作者：
Murray KE;Delic V;Ratliff WA;Beck KD;Citron BA
在1990年至1991年部署到海湾战争的近70万名退伍军人中，约有30%报告说经历了各种症状，包括学习和记忆困难，抑郁和焦虑，以及神经退行性疾病的发病率增加。乙酰胆碱酯酶（AChE）抑制剂的联合毒物暴露已被广泛研究作为一个可能的风险因素。在这项研究中，我们模拟了海湾战争暴露在雄性C57 Bl/6 J小鼠与同时管理的三种化学品牵连的暴露危害海湾战争退伍军人：溴化吡啶斯的明，抗沙林预防;毒死蜱，有机磷杀虫剂;和驱虫剂N，N-二乙基-间甲苯酰胺（避蚊胺）。每天暴露两周后，我们通过全转录组测序（RNA-Seq）检测了海马分离株基因表达的变化。海马相关的空间记忆与Y-迷宫任务进行了评估。我们假设，对神经元健康很重要的基因因毒物引起的损伤而失调，这些有害的炎症基因表达谱可能导致慢性神经退行性变。我们发现了指示促炎反应的基因的失调和与神经元健康相关的基因的下调以及几个重要的立即早期基因（IEG），包括Arc和Egr 1，它们都减少了约1.5倍。暴露于PB + CPF + DEET的小鼠对新臂的偏好降低了1.6倍，表明空间记忆受损。在急性时间点观察到的差异表达的基因可能会提供深入了解海湾战争疾病的病理生理学和进一步解释慢性神经退行性病变后毒物暴露。
Approximately 30% of the nearly 700,000 Veterans who were deployed to the Gulf War from 1990 to 1991 have reported experiencing a variety of symptoms including difficulties with learning and memory, depression and anxiety, and increased incidence of neurodegenerative diseases. Combined toxicant exposure to acetylcholinesterase (AChE) inhibitors has been studied extensively as a likely risk factor. In this study, we modeled Gulf War exposure in male C57Bl/6J mice with simultaneous administration of three chemicals implicated as exposure hazards for Gulf War Veterans: pyridostigmine bromide, the anti-sarin prophylactic; chlorpyrifos, an organophosphate insecticide; and the repellant N,N-diethyl-m-toluamide (DEET). Following two weeks of daily exposure, we examined changes in gene expression by whole transcriptome sequencing (RNA-Seq) with hippocampal isolates. Hippocampal-associated spatial memory was assessed with a Y-maze task. We hypothesized that genes important for neuronal health become dysregulated by toxicant-induced damage and that these detrimental inflammatory gene expression profiles could lead to chronic neurodegeneration. We found dysregulation of genes indicating a pro-inflammatory response and downregulation of genes associated with neuronal health and several important immediate early genes (IEGs), including Arc and Egr1, which were both reduced approximately 1.5-fold. Mice exposed to PB + CPF + DEET displayed a 1.6-fold reduction in preference for the novel arm, indicating impaired spatial memory. Differentially expressed genes observed at an acute timepoint may provide insight into the pathophysiology of Gulf War Illness and further explanations for chronic neurodegeneration after toxicant exposure.
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影响因子：
15.9
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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Tourtellotte, WG
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3.3
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通讯作者：
Sullivan K