Proteomic CNS Profile of Delayed Cognitive Impairment in Mice Exposed to Gulf War Agents
Proteomic CNS Profile of Delayed Cognitive Impairment in Mice Exposed to Gulf War Agents
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DOI：
10.1007/s12017-011-8160-z
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发表时间：
2011-12-01
影响因子：
3.5
通讯作者：
Crawford, Fiona
中科院分区：
文献类型：
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作者：
Abdullah, Laila;Crynen, Gogce;Crawford, Fiona
海湾战争病 (GWI) 是一种具有中枢神经系统 (CNS) 症状的慢性多症状疾病，目前尚无治疗方法。现在认为，同时接触海湾战争 (GW) 制剂，包括溴化吡斯的明 (PB) 和氯菊酯 (PER) 等杀虫剂，是导致 GWI 病因的关键因素。在本研究中，采用蛋白质组学方法来表征与 PB 和 PER 联合暴露相关的神经行为和神经病理学变化所伴随的生物分子紊乱。与仅接受媒介物的对照小鼠相比，急性暴露于 PB 和 PER 超过 10 天的小鼠表现出焦虑样行为、精神运动问题和迟发性认知障碍的增加。蛋白质组学分析显示，与对照组相比，接触 GW 剂的小鼠大脑中与脂质代谢和分子运输相关的蛋白质发生了变化。与内分泌和免疫系统相关的蛋白质也发生了改变，这些系统的功能障碍是 GWI 的一个显着特征。与对照小鼠相比，GW 剂暴露小鼠中星形胶质细胞增生的存在进一步表明免疫系统失衡，正如在 GWI 中观察到的那样。这些研究为驱动这种复杂疾病晚期病理的分子紊乱提供了广阔的视角。评估这些生物学功能在 GWI 中的潜在作用将有助于确定可用于开发针对 GWI 的新型疗法的分子途径。
Gulf War Illness (GWI) is a chronic multisymptom condition with a central nervous system (CNS) component, for which there is no treatment available. It is now believed that the combined exposure to Gulf War (GW) agents, including pyridostigmine bromide (PB) and pesticides, such as permethrin (PER), was a key contributor to the etiology of GWI. In this study, a proteomic approach was used to characterize the biomolecular disturbances that accompany neurobehavioral and neuropathological changes associated with combined exposure to PB and PER. Mice acutely exposed to PB and PER over 10 days showed an increase in anxiety-like behavior, psychomotor problems and delayed cognitive impairment compared to control mice that received vehicle only. Proteomic analysis showed changes in proteins associated with lipid metabolism and molecular transport in the brains of GW agent-exposed mice compared to controls. Proteins associated with the endocrine and immune systems were also altered, and dysfunction of these systems is a prominent feature of GWI. The presence of astrogliosis in the GW agent-exposed mice compared to control mice further suggests an immune system imbalance, as is observed in GWI. These studies provide a broad perspective of the molecular disturbances driving the late pathology of this complex illness. Evaluation of the potential role of these biological functions in GWI will be useful in identifying molecular pathways that can be targeted for the development of novel therapeutics against GWI.