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Electro-behavioral phenotype and cell injury following exposure to paraoxon-ethyl in mice: Effect of the genetic background
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2018-05-22 , DOI: 10.1016/j.cbi.2018.05.009
Benjamin Baccus , Stéphane Auvin , Frédéric Dorandeu

Organophosphorus compounds (OP) are irreversible inhibitors of both central and peripheral cholinesterases (ChE). They still represent a major health issue in some countries as well as a terrorist and military threat. In order to design appropriate medical counter-measures, a better understanding of the pathophysiology of the poisoning is needed. Little to nothing is known regarding the impact of the genetic background on OP-induced seizures and seizure-related cell injury. Using two different mouse strains, Swiss and C57BL/6J, exposed to a convulsing dose of the OP pesticide paraoxon-ethyl (POX), our study focused on seizure susceptibility, especially the occurrence of SE and related mortality. We also evaluated the initial neuropathological response and SE-induced cell injury.

Following the administration of 2.4 mg/kg POX, more Swiss mice experienced SE than C57BL/6J (55.6% versus 17.2%) but the duration of their SE, based on EEG recordings, was shorter (64.3 ± 19.5 min versus 180.8 ± 36.8 min). No significant difference was observed between strains regarding mortality (33% versus 14%). In both strains limited cell injury was observed in the medial temporal cortex, the dentate gyrus and the CA3 field without inter-strain differences (Fluorojade C-positive cells/mm2). Conversely, only C57BL/6J mice showed cell injury in the CA1 field. There was no obvious correlation between the number of Fluorojade C-positive cells and the duration of the EEG discharges.

Our work suggests some differences between Swiss and C57BL/6J mice and lay ground to further studies on the impact of strains in the development of central nervous system toxicity of OP.



中文翻译:

小鼠暴露于对氧磷后的电行为表型和细胞损伤:遗传背景的影响

有机磷化合物(OP)是中枢和外周胆碱酯酶(ChE)的不可逆抑制剂。在某些国家,它们仍然是主要的健康问题,也是恐怖和军事威胁。为了设计适当的医学对策,需要对中毒的病理生理学有更好的了解。关于遗传背景对OP诱发的癫痫发作和癫痫相关细胞损伤的影响,了解甚少。我们使用两种不同的小鼠品系,Swiss和C57BL / 6J,暴露于惊厥剂量的OP农药对氧磷(POX),我们的研究重点在于癫痫发作的易感性,尤其是SE的发生和相关的死亡率。我们还评估了最初的神经病理反应和SE诱导的细胞损伤。

施用2.4 mg / kg POX后,瑞士小鼠经历的SE比C57BL / 6J多(55.6%17.2%),但根据EEG记录,他们的SE持续时间更短(64.3±19.5 min vs 180.8±36.8 min )。菌株之间在死亡率方面没有观察到显着差异(33%14%)。在这两种菌株中,在内侧颞皮质,齿状回和CA3区域均观察到有限的细胞损伤,而没有菌株间差异(Fluorojade C-阳性细胞/ mm 2)。相反,只有C57BL / 6J小鼠在CA1区域显示细胞损伤。Fluorojade C阳性细胞数量与EEG放电持续时间之间没有明显的相关性。

我们的工作表明了瑞士小鼠与C57BL / 6J小鼠之间的某些差异,并为进一步研究菌株对OP中枢神经系统毒性发展的影响奠定了基础。

更新日期:2018-05-22
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