A Chronic Longitudinal Characterization of Neurobehavioral and Neuropathological Cognitive Impairment in a Mouse Model of Gulf War Agent Exposure
A Chronic Longitudinal Characterization of Neurobehavioral and Neuropathological Cognitive Impairment in a Mouse Model of Gulf War Agent Exposure
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海湾战争特工暴露小鼠模型中神经行为和神经病理学认知损伤的慢性纵向特征
DOI：
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发表时间：
2016
影响因子：
3.5
通讯作者：
G. Ait
中科院分区：
文献类型：
--
作者：
Z. Zakirova;Gogce Crynen;Samira Hassan;L. Abdullah;Lauren Horne;V. Mathura;F. Crawford;G. Ait
海湾战争病（GWI）是一种慢性多症状疾病，具有中枢神经系统成分，包括记忆障碍以及神经和肌肉骨骼缺陷。先前的研究表明，在第一次波斯湾战争冲突（1990-1991年）中，暴露于海湾战争（GW）制剂，如溴化吡啶斯的明（PB）和氯菊酯（PER），是GWI病因的关键因素。对于本研究，我们使用了我们先前建立的GW药剂暴露小鼠模型（10天PB+PER），并在暴露后11天至22.5个月对小鼠进行了广泛的终身神经行为表征，以解决当前GWI患者群体在暴露后24年所遭受的影响的持续性和慢性性。使用一系列神经行为测试范例评估小鼠，包括旷场测试（OFT）、高架十字迷宫（Elevated Plus Maze）、三腔室测试、桡臂水迷宫（RAWM）和巴恩斯迷宫（BM）测试。我们还在最终行为测试后暴露于GW剂后22.5个月进行了神经病理学分析。我们的研究结果表明，PB+PER暴露小鼠在暴露后13个月的时间点开始表现出神经行为缺陷，并持续到暴露后22.5个月的时间点。此外，在暴露后22.5个月，观察到神经病理学变化，包括暴露小鼠大脑皮质中GFAP染色增加。因此，在我们的模型中明显的持续性神经炎症提供了一个平台，通过该平台可以识别新的生物学途径，与可能适合治疗靶向的紧急结果相关。此外，在这项工作中，我们证实了我们以前的发现，GW剂暴露会导致神经病理学变化，并提出了新的数据，证明增加的去抑制，并在暴露后13个月的PB+PER暴露小鼠缺乏社会偏好。我们还扩展了我们以前的工作，使用一系列神经行为技术来覆盖实验室小鼠的寿命。
Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component that includes memory impairment as well as neurological and musculoskeletal deficits. Previous studies have shown that in the First Persian Gulf War conflict (1990–1991) exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and permethrin (PER), were key contributors to the etiology of GWI. For this study, we used our previously established mouse model of GW agent exposure (10 days PB+PER) and undertook an extensive lifelong neurobehavioral characterization of the mice from 11 days to 22.5 months post exposure in order to address the persistence and chronicity of effects suffered by the current GWI patient population, 24 years post-exposure. Mice were evaluated using a battery of neurobehavioral testing paradigms, including Open Field Test (OFT), Elevated Plus Maze (EPM), Three Chamber Testing, Radial Arm Water Maze (RAWM), and Barnes Maze (BM) Test. We also carried out neuropathological analyses at 22.5 months post exposure to GW agents after the final behavioral testing. Our results demonstrate that PB+PER exposed mice exhibit neurobehavioral deficits beginning at the 13 months post exposure time point and continuing trends through the 22.5 month post exposure time point. Furthermore, neuropathological changes, including an increase in GFAP staining in the cerebral cortices of exposed mice, were noted 22.5 months post exposure. Thus, the persistent neuroinflammation evident in our model presents a platform with which to identify novel biological pathways, correlating with emergent outcomes that may be amenable to therapeutic targeting. Furthermore, in this work we confirmed our previous findings that GW agent exposure causes neuropathological changes, and have presented novel data which demonstrate increased disinhibition, and lack of social preference in PB+PER exposed mice at 13 months after exposure. We also extended upon our previous work to cover the lifespan of the laboratory mouse using a battery of neurobehavioral techniques.
DOI：
10.1073/pnas.96.9.5280
发表时间：
1999-04-27
影响因子：
11.1
作者：
Bach, ME;Barad, M;Kandel, ER
通讯作者：
Kandel, ER
成年小鼠反复接触亚临床剂量的有机磷农药后，海马突触传递和棘的延迟减少。
DOI：
10.1093/toxsci/kfr253
发表时间：
2012
期刊：
Toxicological sciences : an official journal of the Society of Toxicology
影响因子：
--
作者：
Speed,HaleyE;Blaiss,CoryA;Kim,Ahleum;Haws,MichaelE;Melvin,NealR;Jennings,Michael;Eisch,AmeliaJ;Powell,CraigM
通讯作者：
Powell,CraigM