Pathophysiology in a model of Gulf War Illness: Contributions of pyridostigmine bromide and stress
Pathophysiology in a model of Gulf War Illness: Contributions of pyridostigmine bromide and stress
复制标题
DOI：
10.1016/j.psyneuen.2018.07.015
复制
发表时间：
2018-10-01
影响因子：
3.7
通讯作者：
Reagan, L. P.
中科院分区：
文献类型：
--
作者：
Macht, V. A.;Woodruff, J. L.;Reagan, L. P.
海湾战争期间，溴化吡啶斯的明（PB）预防性治疗沿着部署压力可能导致神经和免疫功能的意外改变，导致许多认知缺陷，临床上称为海湾战争病（GWI）。为了测试PB和应激之间的这种相互作用，以下研究使用GWI的啮齿动物模型来检查重复约束应激和PB的组合如何在治疗的最后一天以及治疗后10天和3个月诱导外周胆碱酯酶（ChE）活性、皮质酮（CORT）水平和细胞因子的改变。结果表明，PB急性降低胆碱酯酶活性，但敏感的三个月后选择性地在大鼠进行应激治疗。类似地，虽然应激急性增加CORT水平，但PB/应激条件下的大鼠在延迟的时间点继续表现出CORT升高，表明PB和应激相互作用，在几个外周测量中逐渐破坏稳态。由于记忆缺陷在GWI临床人群中也很常见，我们研究了PB和压力对情境恐惧条件反射的影响。PB加剧了压力诱导的障碍，在治疗后10天的背景恐惧条件反射，但保护免受压力诱导的增强的背景恐惧条件反射在治疗后3个月。总的来说，这些结果提供了关键的洞察力PB和压力如何相互作用，以促进GWI的病理生理进展。
During the Gulf War, prophylactic treatment with pyridostigmine bromide (PB) along with the stress of deployment may have caused unexpected alterations in neural and immune function, resulting in a host of cognitive deficits which have become clinically termed Gulf War Illness (GWI). In order to test this interaction between PB and stress, the following study used a rodent model of GWI to examine how combinations of repeated restraint stress and PB induced alterations of peripheral cholinesterase (ChE) activity, corticosterone (CORT) levels, and cytokines on the last day of treatment, and then 10 days and three months post-treatment. Results indicate that PB decreases ChE activity acutely but sensitizes it by three months post-treatment selectively in rats subjected to stress. Similarly, while stress increased CORT levels acutely, rats in the PB/stressed condition continued to exhibit elevations in CORT at the delayed time point, indicating that PB and stress interact to progressively disrupt homeostasis in several peripheral measures. Because memory deficits are also common in clinical populations with GWI, we examined the effects of PB and stress on contextual fear conditioning. PB exacerbates stress-induced impairments in contextual fear conditioning ten days post-treatment, but protects against stress-induced augmentation of contextual fear conditioning at three months post-treatment. Collectively, these results provide critical insight as to how PB and stress may interact to contribute to the pathophysiological progression of GWI.