Repeated stress in combination with pyridostigmine Part II: Changes in cerebral gene expression
Repeated stress in combination with pyridostigmine Part II: Changes in cerebral gene expression
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DOI：
10.1016/j.bbr.2008.08.032
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发表时间：
2009-02-11
影响因子：
2.7
通讯作者：
Fauquette, William
中科院分区：
文献类型：
--
作者：
Barbier, Laure;Diserbo, Michel;Fauquette, William
有机磷酸盐（OP）是恐怖主义或军事冲突中的潜在威胁。由于其保护胆碱酯酶（ChE）活性免受OP不可逆失活的能力，溴化吡啶斯的明（PB）在第一次波斯湾战争期间被用作预防治疗。为了解释海湾战争退伍军人（GWV）报告的功能障碍，有人建议将PB给予士兵以增强操作应激效应。我们的配套论文（见同一期刊的第1部分）描述了在重复压力条件下进行PB治疗会导致学习和社会行为的长期干扰。本文在成年雄性Wistar大鼠中研究了重复应激和PB治疗对下丘脑和海马基因表达的影响。PB治疗（1.5 mg/kg/天）口服给药前30分钟，每个应力会议，以抑制40%的血液胆碱酯酶的推荐由北约。单独10天的应激诱导下丘脑II-1 α表达降低。单独用PB治疗增加下丘脑中盐皮质激素受体的表达，这意味着PB可以因此改变动物的应激感知。应激-PB动物表现出海马BDNF、TrkB和CamKII α表达的增加，这三个基因与记忆发育有关。作为以前的研究的补充，显示与PB的压力协会的行为和生化影响，我们的数据显示，这种协会的行为影响可能与海马基因组的变化。这些修改的机制及其与GWV报告的记忆障碍的联系仍有待进一步确定。(C)2008 Elsevier B. V.保留所有权利。
Organophosphates (OP) represent a potential threat in terrorism or during military conflicts. Due to its faculty to protect cholinesterase (ChE) activity against irreversible inactivation by OP, pyridostigmine bromide (PB) was used as a prophylaxis treatment during the first Persian Gulf War. To explain dysfunctions reported by Gulf War Veterans (GWV), it was suggested a potentiation of the operational stress effects by PB given to soldiers. Our companion paper (see part 1 in the same journal issue) describes that PB treatment administered in repeated stress conditions results in long-term perturbations of learning and social behaviour. The present paper examines, in adult male Wistar rats, consequences of the association of repeated stress and PB treatment on gene expression in hypothalamus and hippocampus. PB treatment (1.5 mg/kg/day) was orally administered 30 min before each stress session to inhibit 40% of blood ChE as recommended by NATO. 10 days of stress alone induce a decrease in hypothalamic II-1 alpha expression. Treatment with PB alone increases mineralocorticoid receptor expression in hypothalamus which means that PB may thus modify stress perception by animals. Stressed-PB animals showed increase in hippocampal expression of BDNF, TrkB and CamKII alpha, three genes implicated in memory development. As a supplement to previous studies showing behavioural and biochemical effects of the association of stress with PB, our data reveal that behavioural effects of this association may be linked with genomic changes in hippocampus. Mechanisms underlying these modifications and their link with memory disturbances reported by GWV remain to be further determined. (C) 2008 Elsevier B.V. All rights reserved.