Sustained alterations in neuroimmune gene expression after daily, but not intermittent, alcohol exposure.
Sustained alterations in neuroimmune gene expression after daily, but not intermittent, alcohol exposure.
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每天但不是间歇性酒精暴露后，神经免疫性基因表达的持续改变。
DOI：
10.1016/j.brainres.2016.05.027
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发表时间：
2016-09-01
期刊：
影响因子：
2.9
通讯作者：
Deak T
中科院分区：
文献类型：
--
作者：
Gano A;Doremus-Fitzwater TL;Deak T
急性乙醇中毒与神经免疫基因表达的快速变化（RANGE）相关，包括白细胞介素（IL）-6和B细胞抑制剂α（I κ B α）中κ轻链多肽基因增强子的核因子增加，以及IL-1 β和肿瘤坏死因子（TNF）α的抑制，但对最初几次乙醇暴露中细胞因子的适应性知之甚少。因此，目前的研究检查中枢细胞因子中毒（3小时后乙醇）后，2，4或6胃内乙醇的挑战（4 g/kg）交付无论是每天或每隔一天（EOD）。随后进行血液乙醇浓度（BECs）和皮质酮的分析，以确定是否乙醇交付的时间表将改变亚急性乙醇暴露的药代动力学，或一般敏感性。正如预期的那样，乙醇导致海马、杏仁核和终纹床核（BNST）中IL-6和I κ B α基因表达的显著增加，而IL-1 β和TNF α则受到抑制，从而重复了我们先前的工作。在所有结构中，IL-6和I κ B α的乙醇依赖性增加仍然显著-即使在乙醇处理6天后。当在EOD给予这些剂量时，观察到BNST中的IL-6适度增加，仅在海马中抑制TNF α和IL-1 β。BEC分析显示，在4次EOD暴露后，乙醇的含量有小幅但显著的减少-这一效果在6次每日插管后输送乙醇时没有观察到。这些发现表明，乙醇诱导的RANGE效应不仅仅是乙醇负荷本身的函数，并强调了乙醇给药间隔在确定酒精的神经免疫后果中的关键作用。
Acute ethanol intoxication is associated with Rapid Alterations in Neuroimmune Gene expression (RANGE), including increased Interleukin (IL)-6 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), and suppressed IL-1β and Tumor necrosis factor (TNF) α, yet little is known about adaptations in cytokines across the first few ethanol exposures. Thus, the present studies examined central cytokines during intoxication (3 h post-ethanol) following 2, 4 or 6 intragastric ethanol challenges (4 g/kg) delivered either daily or every-other-day (EOD). Subsequent analyses of blood ethanol concentrations (BECs) and corticosterone were performed to determine whether the schedule of ethanol delivery would alter the pharmacokinetics of, or general sensitivity to, subacute ethanol exposure. As expected, ethanol led to robust increases in IL-6 and IκBα gene expression in hippocampus, amygdala and bed nucleus of the stria terminalis (BNST), whereas IL-1β and TNFα were suppressed, thereby replicating our prior work. Ethanol-dependent increases in IL-6 and IκBα remained significant in all structures—even after 6 days of ethanol. When these doses were administered EOD, modest IL-6 increases in BNST were observed, with TNFα and IL-1β suppressed exclusively in the hippocampus. Analysis of BECs revealed a small but significant reduction in ethanol after 4 EOD exposures — an effect which was not observed when ethanol was delivered after 6 daily intubations. These findings suggest that ethanol-induced RANGE effects are not simply a function of ethanol load per se, and underscore the critical role that ethanol dosing interval plays in determining the neuroimmune consequences of alcohol.